The World Health Organization (WHO) model of 'age-friendly cities' emphasizes the theme of supportive urban environments for older citizens. These defined as encouraging 'active ageing' by 'optimizing opportunities for health, participation and security in order to enhance quality of life as people age' (WHO, Global Age-friendly Cities, 2007). The goal of establishing age-friendly cities should be seen in the context of pressures arising from population ageing and urbanisation. By 2030, two-thirds of the world's population will reside in cities, with - for urban areas in high-income countries - at least one-quarter of their populations aged 60 and over. This development raises important issues for older people: To what extent will cities develop as age-friendly communities? Will so-called global cities integrate or segregate their ageing populations? What kind of variations might occur across different types of urban areas? How are different groups of older people affected by urban change? The 'age-friendly' city perspective has been influential in raising awareness about the impact of population ageing. Against this, the value of this approach has yet to be assessed in the context of modern cities influenced by pressures associated with global social and economic change. The IPNS has four main objectives: first, to build a collaborative research-based network focused on understanding population ageing in the context of urban environments; second to develop a research proposal for a cross-national study examining different approaches to building age-friendly cities; third to provide a systematic review of data sets and other resources of relevance to developing a research proposal on age-friendly cities; fourth, to develop training for early career resarchers working on ageing and urban issues. The network represents the first attempt to facilitate comparative research on the issue of age-friendly cities. It builds upon two meetings held at the Universities of Keele and Manchester in 2011 that sought to establish the basis for cross-national work around the 'age-friendly' theme. The IPNS represents brings together world class research groups in Europe, Hong Kong and North America, professionals concerned with urban design and architecture, and leading NGOs working in the field of ageing. A range of activities have been identified over the two-year funding period: (1) Preparation of research proposals for a cross-national study of approaches to developing age-friendly urban environments. (2) Two workshops to specify theoretical and methodological issues raised by demographic change and urbanisation. (3) A Summer School exploring links between data resources of potential relevance to the ageing and urbanisation theme and which might underpin research proposals. (4) Master classes for network members from key researchers in the field of urbanisation and ageing. (5) A workshop with a user-based theme developing older people's participation in research on building age-friendly communities. (6) Themed workshops (face-to-face and via video-link) to identify research and policy gaps drawing on inter-disciplinary perspectives The IPNS will be sustained in a variety of ways at the end of the funding period. A collaborative research proposal as well as one to maintain the network will be major outputs from the project and work with potential funding bodies will continue after 2014. Dissemination activities will continue through professional networks, symposia at major international conferences, and involvement in expert meetings. The project will continue to be advertised through the maintenance of a website maintained by the host UK HEI. The project will continue to make a contribution to policy development around the theme of age-friendly cities, notably with the main NGOs working in the field.

The duplication of genes provides new genetic material that can be used for novel functions, allowing plants and animals to evolve biological innovations and adapt to environmental conditions. Whole genome duplication (WGD) is arguably the most dramatic mechanism for duplication, resulting in the production of a new copy of every gene in the nuclear genome. Around 430 million years ago, spiders and scorpions diverged from a common ancestor that had experienced a WGD. The retained duplicated genes from this WGD event (genes called ohnologs) can still be found in the genomes of the approximately 45,000 species of these animals alive today and may have contributed to their adaptation and diversification. Since then, some families of Synspermiata spiders have undergone at least two additional WGDs within a single lineage, reflecting a similar series of WGDs in vertebrates. This presents an opportunity to compare these events to determine whether there are general principals shaping the outcomes of WGDs and their contribution to animal diversification. In addition, Synspermiata represent a wide diversity of spiders that are understudied and poorly understood Therefore, the aims of this project are to identify spider ohnologs after multiple WGDs, explore whether and how they have contributed to the evolutionary success of these animals, and compare the outcomes of these events to repeated WGDs in vertebrates. We will first collect and carry out the first large scale detailed study of the morphology of Synspermiata spiders to better understand their evolution and phenotypic diversity. In parallel, we will identify the ohnologs that have been retained in spider groups after WGDs by comparing the repertoire and arrangement of the duplicated genes in these animals with relatives where there is no evidence of additional WGDs. As part of this aim, we will sequence the genomes of Synspermiata spiders that have undergone one (Pholcus phalangioides, Scytodes thoracica and Loxosceles reclusa), and two (Oonops pulcher, Segestria senoculata and Dysdera crocata) WGD, as well as the transcriptomes of Caponiidae species with two (Orthonops zebra) or three (Calponia harrisonfordi) WGDs. Since relatively little is known about these spiders this will provide new insights into the biology of these animals as well as their genome evolution. We will then compare the repertoires of genes retained after WGD between spiders and vertebrates to determine whether there are any similarities in the aftermath of these events. This information will help us to better understand the general consequences of WGD and the principles underlying their outcomes in terms of genes being preferentially retained or lost again. Identification of ohnologs will also allow us to ask if these genes have been subject to sub-, neofunctionalisation or specialisation during spider development and if their expression is associated with morphological diversification. Overall our project will provide new insights into the genomes of spiders and how WGDs in these animals have contributed to their morphological evolution. Our data will also allow comparisons to WGD events in other animals, including vertebrates, to better understand the general consequences of these events and their contribution to animal adaptation and diversification.

This project investigates the difference between the time of the clock and the lived time of experience. We live in a world dominated by the time of the clock, yet many aspects of life have a different rhtyhm and temporality. The time of community, especially, is very often more complex and differentiated that standardised clock time. A co-inquiry of researchers from a range of disciplines in the arts and humanities and practioners in community organisations will explore ways by which communities can acquire a more open and diversified relation to time; they will approach this question both from a theoretical point of view as well as from a practice- and intervention-based point of view. As such the project will make a significant contribution to developing a concrete ethics and culture of temporal diversity. The project is a co-inquiry between researchers and community organisations and the impact runs therefore in both ways: we aim to develop interventions that will enable communities to reflect on common assumptions about time, but also recognise that like any other community, the research and knowledge production community itself is driven by certain assumptions about time which are in need of examination, and so this project will also explore what the research community can learn from its engagement with other communities. In addition to the theoretical research, the project contains three 'pathfinders' for community engagement on the issue of time: 1. This strand considers contextualisation of interventions on temporal diversity. What have alternative clocks looked like, such as the Doomsday Clock, the Clock of the Long Now and the 100 Months Clock, how have they affected communities, which methods, justifications and broader impacts do they have? What can we learn from previous community interventions by artists, art organisations but also others? The strand will consider both older and recent interventions. 2. The question of the diversity of time will also be explored in a community project about 'the score'. The score is a convergence between measured time (regular beat) and lived time (unique patterns of individual composition), expressed visually through the grid/frame in notation/drawing as the structural principle and the line as depicting movement. The experimental score (in music and the visual arts) is an embodiment of freedom within constraint, offering the potential for a different, variable relationship with time from the purely mechanical. 3. In a psychoanalytical study the experiences of children with time, and how ways of dealing with time can include and exclude, will be examined in the context of a Special Needs School. The importance of issues of temporality for the building of sustainable communities in which people can feel at home from an early age will be the focus here. The research and analytical findings will be connected to an artistic practice intervention on alternative clocks - clocks that measure different temporalities from normal clock time - which will be designed in collaboration with the school and will take place at the school (including a workshop for the school community). Throughout the project the three strands will give input to each other, will learn from and reflect on each other's practice through regular workshops and will contribute to, and use the findings of, the theoretical research activity (co-inquiry). The project will consist of research activity, exhibitions and interventions, an on-line forum and blog, workshops and a conference.

Carbon is one of the essential elements required for life to exist, alongside energy and liquid water. In contrast to other parts of the Earth's biosphere, cycling of carbon compounds beneath glaciers and ice sheets is poorly understood, since these environments were believed to be devoid of life until recently. Significant populations of micro-organisms have recently been found beneath ice masses (Sharp et al., 1999; Skidmore et al., 2000; Foght et al., 2004). Evidence shows that, as in other watery environments on Earth, these sub-ice microbes are able to process a variety of carbon forms over a range of conditions, producing greenhouse gases, such as CO2 and CH4 (Skidmore et al., 2000). Almost nothing is known about 1) the range of carbon compounds available to microbes beneath ice, 2) the degree to which they can be used as food by microbes and 3) the rates of utilisation and the full spectrum of products (e.g. gases). This information is important for understanding the global carbon cycle on Earth. The fate of large amounts of organic carbon during the advance of the glaciers over the boreal forest during the last ice age (Van Campo et al., 1993), for example, is unknown and is likely to depend fundamentally on microbial processes in sub-ice environments. Current models of Earth's global carbon cycle assume this carbon is 'lost' from the Earth's system (Adarns et al., 1990; Van Campo et al., 1993; Francois et al., 1999). The possibility that it is used by subglacial microbes and converted to CO2 and CH4 has not been considered. This may have potential for explaining variations in Earth's atmospheric greenhouse gas composition over the last 2 million years. Sub-glacial environments lacking a modern carbon supply (e.g. trees, microbial cells) may represent ideal model systems for icy habitats on other terrestrial planets (e.g. Mars and Jupiter moons; Clifford, 1987; Pathare et al. 1998; Kivelson et al. 2000), and may be used to help determine whether life is possible in these more extreme systems.

Myeloma is a cancer of the bone marrow which affects over 5000 new patients a year in the UK, is largely incurable, and the vast majority of patients will eventually die of their disease. We now understand the immune system has an important part to play in myeloma. The immune system is a complex army of cells that the body uses to protect itself. T-cells are part of this army and are used to kill and stop infections. T-cells don't usually attack cancers for two main reasons. Firstly, T-cells do not recognize myeloma cells as being abnormal (since they come from our own cells and are not infected) and hence do not target them. Secondly, cancer cells have found ways to protect themselves- often by surrounding themselves with proteins and cell types which block the immune system. These so called immune-suppressive mechanisms are well described in myeloma. Immunotherapy are new treatments which redirect the immune system to fight cancer. Recently a method has been developed to obtain T-cells from cancer patients, modify them to kill cancer and then return them to patients as a drip. This strategy overcomes the lack of recognition of cancer by T-cells and these engineered T-cells live and grow in the patient and attack cancer cells as if they were infected cells (called chimeric antigen receptors or CAR T-cells). This has been successful in leukemia and lymphoma and although myeloma patients do respond to CAR T-cells, not as well. The reason why CAR T-cell therapy doesn't work very well in myeloma is due to the second problem. The immune-suppressive mechanisms that stop normal T-cells from recognising and killing cancer cells likely affect modified T-cells too- reducing their killing potential. There are two possible strategies to combat this: first, several chemical and protein drugs can disrupt the ways cancer cells develop to protect themselves from the immune system. CAR T-cells can be combined with such drugs. Alternatively, CAR T-cells can be engineered in additional ways to make them resistant to suppression. However, we do not yet have enough knowledge of the immune suppressive mechanisms in myeloma, or of how they can affect the CAR T-cells. So we do not know which are the key suppressive pathways to overcome. There are also too many available drugs and chemicals so that it is not feasible to test all possible combinations and there are currently no established ways of testing this on the benchtop or in mice. The aim of my project is to gain knowledge of the mechanisms by which myeloma evades CAR T-cells. I will then use this knowledge to find the best way to combine CAR T-cells with strategies to overcome the suppressive immune system to make them as effective as possible in treating myeloma. During my PhD, I developed a CAR T-cell strategy for myeloma which is now being tested in the first CAR T-cell trial for myeloma patients in the UK. I will start by studying the immune cells from patients on the clinical study who are being treated with CAR T-cells, so I can learn how the CAR T-cells behave after entering the patients. I will be able to compare the immune system in patients who respond, to those who do not. This will help us to understand which are the immune cells and immune suppressive mechanisms that are important if patients are to respond to CAR T-cell therapy. I will also study cells in the laboratory, combining different types of immune cells, to test the behaviour of CAR T-cells in killing myeloma cells. I will develop and use a mouse model of myeloma, that has an intact immune system, as this model will allow me to study in more detail how the myeloma immune system interacts with CAR T-cells than has been possible before. The results of these studies will provide important information to help design and then test treatments that could be used with CAR T-cells to make them more efficient at eradicating myeloma cells, and even potentially cure this cancer.