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Theme-based Research Scheme 2019/20 (Ninth Round) Layman Summaries of Projects Funded

Theme 1: Promoting Good Health
Project Title: Control of Influenza: Individual and Population Immunity
Project Coordinator: Prof Benjamin Cowling (HKU)

Abstract
Influenza is major threat to global public health. Seasonal influenza viruses cause annual epidemics with significant morbidity and mortality but existing vaccines are not optimal. Influenza can vary in severity from asymptomatic to lethal, and disease severity can be influenced by viral and host factors, importantly the level of prior immunity. Pandemics arise at unpredictable intervals but spread worldwide within weeks or months and conventional vaccines cannot be deployed in time to contain initial epidemics. As a travel hub situated at an epicenter of zoonotic and pandemic emergence, Hong Kong is particularly challenged by emerging and re-emerging infectious diseases, especially influenza. Over the past 15 years, we have established a world-leading multi-disciplinary influenza research program in Hong Kong, which has contributed to public health responses locally and globally. We propose to build on this foundation and further strengthen our capacity to address important research questions in influenza virus immunity and transmission with a long-term mission to achieve more effective and efficient control of this disease. Our own studies have shown that hemagglutination inhibition antibody titers, which are the current correlate of protection against influenza, only explain around 57% of the protective effect of conventional inactivated vaccines. These antibodies are even less correlated with the protection provided by live attenuated influenza vaccines or new vaccines currently in development. Therefore, key knowledge gaps include: (a) what are the immune correlates of protection against influenza infection or severe disease; (b) which of these are induced temporarily or permanently by prior natural infection or different types of vaccination; (c) what are the factors which contribute to increased susceptibility of populations to influenza epidemics; d) how should we best deploy new and existing influenza vaccines to reduce the impact of influenza epidemics and pandemics; and (e) what are other immunological mechanisms relevant to the development and evaluation of new influenza vaccines. New mechanisms of humoral and cell-mediated immune protection have been elucidated in the past decade but their relative contribution to protection remain to be further defined. The relevance of these and other previously undefined mechanisms for protection against infection and disease in humans is the major knowledge gap which we plan to address. This program will generate high quality research, intellectual property, and real-time data to inform local, national and global health policy, train the next generation of scientists, and maintain and enhance Hong Kong's world-leading status in influenza research.


Theme 1: Promoting Good Health
Project Title: Fighting Disease Recurrence and Promoting Tissue Repair after Liver Transplantation: Translating Basic Discoveries to Clinical Excellence
Project Coordinator: Prof Chung-mau Lo (HKU)

Abstract
During the past two decades, we have successfully built an internationally renowned liver transplantation centre in Hong Kong. We pioneered in living donor liver transplantation (LDLT) using the right lobe liver graft in the world. This surgical innovation has successfully rescued almost 1400 patients with end-stage liver diseases and liver cancer in this sole transplantation center of Hong Kong. However, the prevalence of hepatitis B virus (HBV) infection, high incidence of liver cancer (Hepatocellular carcinoma-HCC) and the shortage of deceased organ donors in Hong Kong has burdened heavily on the healthcare systems. We face the grand challenges of recurrent diseases and liver graft injury after transplantation. The proposed TRS aims to improve the long-term outcomes of liver transplantation by tackling two major recurring diseases including cancer recurrence and HBV reactivation in Hong Kong through exploring underlying mechanisms, identifying efficacious biomarkers, and developing potential treatments by integrating basic, translational and clinical research. We hypothesize that novel approaches promoting liver tissue repair and regeneration will abrogate the limit of donor organ shortage. We have established a Biobank with comprehensive clinical database for more than 20 years with around 50000 tissue and liquid biopsies from almost 1400 adult recipients with 100% of patient follow-up. Based on this Biobank, we will establish a modeling system that integrates high-throughput sequencing data and biology/immunology parameters not only for predicting disease recurrence and prognoses, but also for therapeutic guidance. We will develop cost-effective immunotherapies as novel prophylaxis, especially for the pre-treatment of living donors, to benefit the recipients' long-term outcomes with both societal and economic impact. The proposed multidisciplinary collaborative project will not only strengthen our local and regional excellence, but also enhance Hong Kong as an internationally leading centre of excellence in liver transplant. In addition to patient and economic benefits, this project will cement Hong Kong's international stature in science, medicine and education.


Theme 2: Developing a Sustainable Environment
Project Title: A Paradigm-shifting, Fully-integrated, Compact Wastewater-to-resource Facility (WWRF)
Project Coordinator: Prof Guang-hao Chen (HKUST)

Abstract
Water scarcity is threatening the sustainable growth of cities worldwide. In Hong Kong, importing freshwater from mainland China (meeting about 70% of the total freshwater demand) and adopting a dual-pipe system to supply seawater for toilet flushing (replacing 22% of the total freshwater demand) and potable water for other commercial and domestic purposes have so far been effective in combating water scarcity. This dual-pipe system, however, is expensive to maintain; and the cost of importing water rises by 6% every year. A conventional solution to urban water scarcity is to reuse wastewater wherever possible. However, three major problems exist. 1) The current reuse practice simply adds post-treatments to existing wastewater treatment schemes. These additional post-treatments demand space, requires costly chemical dosing and consumes extra energy. 2) Most wastewater treatment technologies in use today are not efficient in terms of space requirements, energy consumption, and resource recovery, due to the pollutants are diluted. 3) Most of the current technologies produce large volumes of solid waste and brine wastewater which are difficult to treat. A much better solution is needed. In this project, the world's top scientists in water science and technology have teamed up with leading researchers in membrane science, chemistry, toxicology, and engineering to develop a new ground-breaking water system for wastewater treatment and effluent reuse/recycle, with the ultimate goal of mitigating water scarcity. The resulting fully-integrated, compact WasteWater-to-Resource Facility (WWRF) will feature novel technologies (namely new membrane, chemical and biological treatment and resource recovery technologies) for significant production of potable water and valuable biochemicals from saline wastewater, with minimal brine and biological sludge.


Theme 2: Developing a Sustainable Environment
Project Title: SureFire: Smart Urban Resilience and Firefighting
Project Coordinator: Prof Asif Sohail Usmani (PolyU)

Abstract
The Guangdong-Hong Kong-Macao Greater Bay area has an urban environment of the high-density population that is inherently more sustainable and ideally suits smart city technologies. Increasing numbers of fires in tall buildings around the world have shown that the evolution of the built environment has changed the nature of the threat from fire. Urban environments are exposed to greater risk as prescriptive fire safety strategies are no longer fit for purpose. Firefighters are left facing an unpredictable hazard, that they are neither trained nor equipped to deal with, as the London Grenfell Tower fire in 2017 tragically demonstrated. On top of the human cost, costs due to losses from fire are estimated at approximately 1 per cent of global GDP per year. Therefore, while sustainability is paramount, a society's resilience to disasters should also be a critical consideration in sustainable urban development. An urban environment that is not resilient cannot be considered sustainable.

A-posteriori investigation of major disasters has invariably exposed the inadequacy of response, usually caused by poor decisions due to a lack of useful information from the incident location. Judicious exploitation of smart city technologies can make urban environments more resilient. Smart cities contain complex data generating networks that enable real-time monitoring of the performance of urban environments. Proper analysis of this data can deliver information that continuously determines the state and evolution of systems and diagnoses emergent pathologies. Effective diagnosis requires professionals capable of curating this data and a framework for translating it into useful and actionable information and knowledge. Fundamental research can help achieve a workable prototype for emergency response on the scale of an urban environment, such as Hong Kong and the Greater Bay Area.

This proposal has gathered a multi-disciplinary team with leading local and international researchers and research laboratories, a government agency (FSD), and multiple high-tech companies to find answers to the fundamental research questions required to develop the foundational technology for a smart firefighting system that takes advantage of the rapidly evolving technology landscape of cyber-physical systems. Implementation of such a system for smart firefighting can help Hong Kong achieve the status of the world's leading smart city.


Theme 4: Advancing Emerging Research and Innovations Important to Hong Kong
Project Title: Research and Development of Artificial Intelligence in Extraction and Identification of Spoken Language Biomarkers for Screening and Monitoring of Neurocognitive Disorders
Project Coordinator: Prof Helen Mei-ling Meng (CUHK)

Abstract
Population ageing is a global concern. According to WHO, our world's population aged 60+ will nearly double to 22% by 2050, while Hong Kong's population aged 65+ will rise to 35%. Ageing is accompanied by various high-burden geriatric syndromes, which escalate public healthcare expenditures. This situation, coupled with a shrinking workforce and narrowing tax base, jeopardizes our society's sustainability. Neurocognitive disorders (NCD) – including age-related cognitive decline, mild cognitive impairment, and various types of dementia – are particularly prominent in older adults. Dementia has an insidious onset followed by gradual, irreversible deterioration in memory, communication, judgment, and other domains; care costs are estimated at USD 1 trillion today and are expected to double by 2030. This presents a dire need for better disease screening and management. NCD diagnoses and monitoring are largely conducted by clinical professionals face-to-face using neuropsychological tests. Such testing is limited due to clinician shortages; capturing snapshots of cognition that ignore intra-individual variability; subjective recall of cognitive functioning; inter-rater variability in assessment; and language/cultural biases. To address these issues, we will develop an automated, objective, highly accessible evaluation platform based on inexpensively acquirable biomarkers for NCD screening and monitoring. Platform accessibility enables active, remote monitoring, and the generation of patient alerts for prompt treatment between clinical visits. Collecting individualized "big data" over time enables flagging of subtle changes in cognition for early detection of cognitive decline. These actions will prevent under-diagnosis, enhance disease management, delay institutionalization, and lower care costs. NCD often manifests in communicative impairments. Hence, we target spoken language biomarkers – non-intrusive alternatives to blood tests and brain scans for NCD screening and monitoring. Spoken language can be easily captured remotely. Speech event records (e.g. latencies, dysfluencies) at millisecond resolutions enable sensitive cognitive assessments. We will develop Artificial Intelligence (AI)-driven technologies to automatically extract spoken language biomarkers. Our work is novel in its comprehensive dimensional coverage of conversational spoken language dialogs (from hesitations to dialog coherence), using fit-for-purpose deep learning techniques for feature extraction and selection. Our systems will be highly adaptable across environments to ensure consistent, objective NCD assessments. Our research will offer unprecedented data and technological support for early NCD diagnoses and timely clinical care. This aligns with WHO's plan of making dementia a public health and social care priority at national and international levels. We aim to control the overwhelming burden of NCD through AI-enabled healthcare that better supports patients and caregivers in Hong Kong.