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We are proposing a new and innovative precision approach to the identification of severe infections and sepsis in children. This data-driven approach to diagnosis will overcome many of the limitations of current expert opinion-based triage guidelines. Smart technology has the potential to overcome the barrier of limited clinical expertise in the identification of the child at risk. This mobile health platform, with sensors and data-driven applications, will provide real-time individualised risk prediction to facilitate timely and effective targeted treatment at first contact, regardless of location. This low-cost technology will provide rapid triage in remote areas globally where specialists are not regularly available. We will trigger rapid, highly effective and low-cost interventions such as antibiotics, fluid, oxygen therapy and other special investigations to children determined to be most at risk of sepsis, based on data-driven prediction. Thus, these innovations will improve timely access to life-saving treatments for children in the poorest countries where deaths from infection and sepsis are common. Children in poor families or in populations marginalized by health and social inequities are especially vulnerable to infections. In these children, infection is a major contributor to disability and years of life lost and has a great economic and social cost. Sepsis is the leading cause of death and disability in children, every hour of delay in treatment is associated with greater organ damage and ultimately death. The challenges, especially in poor countries, are the delays in diagnosis and the inability to identify children in urgent need of treatment. To circumvent these challenges, we propose the implementation and evaluation of a trigger tool that will reduce the time to diagnosis and prompt the timely initiation of life-saving treatment. The key innovations are 1) a data-driven approach to rapid diagnosis of sepsis severity and 2) a low-cost digital tagging system to track the time to treatment. The tool will require minimal cost, clinical expertise and training or time to use. The tool will identify high risk children and reduce time to treatment. Our mobile platform (mobile device and dashboard) will create a low-cost, highly scalable solution for children with sepsis.

Changes in biodiversity, both natural and caused by human activities, are intimately tied to changes in ecosystem status. The environment in which species live will affect their chances of movement, survival, and adaptation; for example, abrupt changes in vegetation cover can modify the risk of predation experienced by some species, and therefore change the relative abundance of their populations. But because species express a variety of biological functions, they too change the status of their ecosystem; for example, harmful algal blooms will disrupt the physical and chemical composition of water, which can lead to localized extinctions, and send rippling effects across the ecosystem. As such, the biological and the ecosystemic are indissociably coupled. Nevertheless, effectively coupling models at these scales has proven difficult, because of three core challenges: differences in scale, differences in how models are built, and volume of data required. Biodiversity and ecosystem sciences have made progress on these challenges, and developing a field-specific case study to integrate models and pre-existing work will inform about the feasibility of a more general approach to model coupling. We believe this approach to be necessary for accurately identifying emerging challenges and opportunities in global ecosystem sciences, intrinsically tied to human wellbeing.

It is now clear that any delays in developing an effective vaccine will increase the burden from HIV/AIDS in the parts of the world that can least afford it. In the true spirit of the Global HIV/AIDS Vaccine Enterprise, forums which allow open and transparent exchange of information and data sharing are absolutely needed. We firmly believe that an international scientific conference which aims 1) to address the scientific roadblocks to vaccine development, 2) to identify promising strategies that may help overcome those roadblocks, 3) to encourage open discussions of the most recent results from pre-clinical and clinical vaccine trials and 4) to facilitate the initiation of new collaborations will accelerate the development of a safe and effective HIV vaccine and help the developing world reach the elusive goal of developing an efficacious vaccine to HIV. However, the achievement of this objective is only possible through close collaboration with scientists from countries most affected by the HIV pandemic; scientists and clinicians from affected countries are valued and crucial colleagues in our mission to develop an HIV vaccine and this every possible effort has to be made to integrate this group of scientists in this effort. The AIDS vaccine 2005 has as major objective to ensure that this group is an integral component of the global effort. The topics that will be covered includes: Major scientific obstacles in the field of vaccine development Clinical trials Manipulating and enhancing immune response. Challenges in vaccine development: perspective of developing countries Prophylactic vaccines Neonatal immunity and maternal-fetal transmission Challenges in developing therapeutic vaccines Lessons learned from successful vaccines Immune memory: how to induce and measure B cell and antibody response to HIV Comparison of immune responses in animal and humans Global Enterprise and other collaborative partnerships

G protein-coupled receptors (GPCRs) represent the largest family of cell surface proteins. Agonist binding to GPCRs activates G proteins regulating many cellular effectors. Classically, G protein activation occurs at the plasma membrane and is rapidly terminated by β-arrestin recruitment to the activated GPCRs, promoting G protein uncoupling from receptor, GPCR internalisation and signalling arrest. However, recent studies revealed that upon internalisation, some GPCRs continue to activate G proteins from internal compartments leading to sustained production of second messengers far from the plasma membrane. This different spatiotemporal signalling profile allows distinct cellular functions from the ones occurring at the plasma membrane that can be exploited in the near future to design new pharmacological approaches. My collaborators and I recently observed that for some GPCRs such as the vasopressin type 2 receptor, formation of a GPCR-G protein-β-arrestin complex (baptised megaplex) in internal compartments is required for non-canonical Gs protein signalling. The initial research programme I propose aims to tackle the following important questions underlying this novel signalling mode: 1. Is G protein selectivity different at intracellular compartments vs at plasma membrane? 2. Is megaplex formation restricted to Gs isoform? 3. What is the specific role of β-arrestin within the megaplex? Environmental stimulants (hormones, neurotransmitters) can be compared to keys able to bind to and activate (open) cell surface receptors (locks). When a key opens a lock, proteins detecting this opened lock (called G proteins) are activated at the cell surface leading to specific outcomes. Some proteins (ß-arrestins) are then recruited to remove G proteins from the receptor and bring it inside the cell leading to signalling arrest. Recently, we observed that active G proteins can also be found inside the cell mediating different outcomes than when located at cell surface and that ß-arrestins was promoting receptor signalling inside the cell instead of stopping it. My objective is to explore this new G protein signalling, to learn how ß-arrestins can promote internalised receptor signalling, and determine if they activate other G proteins than the ones at the cell surface. This could lead to development of new medications with less side effects.

The proposed visit has two main aims. The first is to disseminate Interior Traces1 which uses multimedia drama to explore issues in neuroethics to the Canadian Neuroethics community and local public audiences. Dr Whiteley will run a series of screenings, targetingneurology and psychiatry residents, undergraduate students in medicine and law, members of NeuroDevNet2, and the general public, accompanied by Café Scientifique-style discussions. She will also give seminars, and gather feedback that will contribute to a journal submission on the use of fictional narratives to explore bioethical issues. The second aim is to extend Dr Whiteley's previous research on what the representation of brain imaging in popular culture might reveal about anxieties surrounding neural and genetic determinism and identity. She will write up existing research, and collaborate on a new project contributing to our ongoing work atthe National Core for Neuroethics, systematically examining the use of images on websites that sell direct-toconsumer scans and treatments for mental illness and neural disorder. Dr Whiteley's visit will thus contribute new perspectives to the local neuroethics community and public communication landscape, as well as extending her skills and publication record in neuroethics research.