Spatial Methods for Inferring Extremes in Dengue Outbreak Risk in Singapore.

Dengue is a major vector-borne disease worldwide. Here, we examined the spatial distribution of extreme weekly dengue outbreak risk in Singapore from 2007 to 2020. We divided Singapore into equal-sized hexagons with a circumradius of 165 m and obtained the weekly number of dengue cases and the surface characteristics of each hexagon. We accounted for spatial heterogeneity using max-stable processes. The 5-, 10-, 20-, and 30-year return levels, or the weekly dengue case counts expected to be exceeded once every 5, 10, 20, and 30 years, respectively, were determined for each hexagon conditional on their surface characteristics remaining constant over time. The return levels were higher in the country's east, with the maximum weekly dengue cases per hexagon expected to exceed 51 at least once in 30 years in many areas. The surface characteristics with the largest impact on outbreak risk were the age of public apartments and the percentage of impervious surfaces, where a 3-year and 10% increase in each characteristic resulted in a 3.8% and 3.3% increase in risk, respectively. Vector control efforts should be prioritized in older residential estates and places with large contiguous masses of built-up environments. Our findings indicate the likely scale of outbreaks in the long term.

Leave no one behind: A case of ecosystem service supply equity in Singapore.

Urban populations benefit greatly from the ecosystem services provided by urban green and blue spaces. While the equity of provision of and access to urban green and blue spaces has been widely explored, research on equity of ecosystem service provision is relatively scant. Using household level data, our study aims to assess the supply equity of five regulatory ecosystem services in Singapore. We employed linear mixed-effects models and Hot Spot Analysis to analyze their distributional equity across individual households of various demographic characteristics (horizontal inequality), and calculated Gini coefficient for the distribution of PM10 removal service among households categorised into demographic subgroups (vertical inequality). Our results show little evidence of inequitable ecosystem service provision among Singapore's diverse socio-demographic groups. This can be attributed to the early integration of environmental management strategies and meticulous socio-economic desegregation efforts into urban development plans, which maximised provision and maintenance of urban green spaces to all residents.

Fine-scale estimation of effective reproduction numbers for dengue surveillance.

The effective reproduction number Rt is an epidemiological quantity that provides an instantaneous measure of transmission potential of an infectious disease. While dengue is an increasingly important vector-borne disease, few have used Rt as a measure to inform public health operations and policy for dengue. This study demonstrates the utility of Rt for real time dengue surveillance. Using nationally representative, geo-located dengue case data from Singapore over 2010-2020, we estimated Rt by modifying methods from Bayesian (EpiEstim) and filtering (EpiFilter) approaches, at both the national and local levels. We conducted model assessment of Rt from each proposed method and determined exogenous temporal and spatial drivers for Rt in relation to a wide range of environmental and anthropogenic factors. At the national level, both methods achieved satisfactory model performance (R2EpiEstim = 0.95, R2EpiFilter = 0.97), but disparities in performance were large at finer spatial scales when case counts are low (MASE EpiEstim = 1.23, MASEEpiFilter = 0.59). Impervious surfaces and vegetation with structure dominated by human management (without tree canopy) were positively associated with increased transmission intensity. Vegetation with structure dominated by human management (with tree canopy), on the other hand, was associated with lower dengue transmission intensity. We showed that dengue outbreaks were preceded by sustained periods of high transmissibility, demonstrating the potential of Rt as a dengue surveillance tool for detecting large rises in dengue cases. Real time estimation of Rt at the fine scale can assist public health agencies in identifying high transmission risk areas and facilitating localised outbreak preparedness and response.

Comparison of vegetable production, resource-use efficiency and environmental performance of high-technology and conventional farming systems for urban agriculture in the tropical city of Singapore.

Urban farming can improve cities' food security and resilience, but the performance of different farming systems with respect to land and investment constraints has not been systematically investigated. Here, we compared conventional soil-based farming, vertical farming with natural lighting (Vnat), and indoor vertical farming. This study aimed to compare (1) the dynamic production of leafy vegetables over time given the same amount of investment and land constraints, (2) the associated water and energy use, and (3) the global warming potential (GWP) of the urban farming sector if each of the three farming systems was solely used in the tropical city-state of Singapore. A system dynamics (SD) model was constructed to map the potential quantity of leafy vegetables produced, together with the water and energy use of each farming system. The land and monetary investment constraints were set at an additional 0.3% of the total land area of Singapore and an annual investment of SGD 10-20 million (0.001-0.005% of Singapore's annual GDP). Vnat farming was predicted to have the highest production level (110,000 t) and self-sufficiency (76.9% of total demand) by 2050 based on the SD model. This would be >3 times the self-sufficiency level achieved by indoor and soil-based farming systems given the same investment and land constraints. Indoor farming was simulated to use <14% the land area of Vnat while soil-based farming exhausted the additional 0.3% of the land allocated. Indoor farming was also the most energy intensive system, requiring 100 times more than Vnat farming. Comparison of the GHG emission rates showed that indoor farming had the greatest GWP-at 2.51 kg CO2-eq per kg of lettuce produced. Our results suggest that Vnat farming may be the best form of urban farming system to provide large amounts of food in Singapore, considering the production level, the amount of resources used, and the environmental impacts.

Quantifying net loss of global mangrove carbon stocks from 20 years of land cover change.

Mangrove forests hold some of the highest densities of carbon recorded in any ecosystem, but have experienced widespread deforestation through conversion to aquaculture and agriculture. Alongside deforestation, mangroves have shown simultaneous natural expansion in some parts of the world, and considerable investments have been made into restoration programmes. Here we estimate net changes in the global mangrove carbon stock due to land cover change between 1996 and 2016, using data on mangrove deforestation and forestation, and proportional changes in carbon stock during processes of mangrove loss and gain. The global mangrove carbon stock declined by 158.4 Mt (95% CI = -156.8-525.9 Mt); a reduction of 1.8% of the stock present in 1996. Efforts to conserve and restore mangroves appear to have had some success, and - along with natural forestation - have contributed to relatively low net losses of mangrove carbon stocks over two decades.

Demographic biases in engagement with nature in a tropical Asian city.

Urban residents can benefit from spending time in outdoor spaces and engaging with nature-related activities. Such engagement can improve health and well-being, support community cohesion, and improve environmentally-friendly behaviours. However, engagement with nature may not be equal amongst different members of society. We investigated individual variation in engagement with nature in Singapore, a high-density city in tropical Southeast Asia. Through a survey of 1000 residents, we analysed relationships between demographic factors such as age, income, and sex, and the frequency of visitation to different ecosystem types, and the frequency of engagement with different nature-related activities. Parks and neighbourhood open spaces were among the most commonly-visited outdoor spaces, with nature reserves and other natural areas being visited less frequently. Common activities included sitting outdoors, art and photography, and running, while hiking and nature recreation were less frequent. In contrast with previous studies, we found relatively small differences among different groups of the population in their preferred types of outdoor activities. Older people, those with lower incomes, and without degrees were less likely to visit most types of outdoor space and engage with most types of nature-related activities. In the case of nature reserves, the distance from the visitor's home had a significantly negative influence on the frequency of visitation. These findings demonstrate that the benefits of engagement with nature are not equally enjoyed by all demographic groups, and that some groups lack engagement across the board. Strategies to increase nature engagement in tropical cities could include increasing the local availability and accessibility of different types of outdoor space, and education and public outreach programmes to encourage participation.

Global trends in mangrove forest fragmentation.

Fragmentation is a major driver of ecosystem degradation, reducing the capacity of habitats to provide many important ecosystem services. Mangrove ecosystem services, such as erosion prevention, shoreline protection and mitigation of climate change (through carbon sequestration), depend on the size and arrangement of forest patches, but we know little about broad-scale patterns of mangrove forest fragmentation. Here we conduct a multi-scale analysis using global estimates of mangrove density and regional drivers of mangrove deforestation to map relationships between habitat loss and fragmentation. Mangrove fragmentation was ubiquitous; however, there are geographic disparities between mangrove loss and fragmentation; some regions, like Cambodia and the southern Caribbean, had relatively little loss, but their forests have been extensively fragmented. In Southeast Asia, a global hotspot of mangrove loss, the conversion of forests to aquaculture and rice plantations were the biggest drivers of loss (>50%) and fragmentation. Surprisingly, conversion of forests to oil palm plantations, responsible for >15% of all deforestation in Southeast Asia, was only weakly correlated with mangrove fragmentation. Thus, the management of different deforestation drivers may increase or decrease fragmentation. Our findings suggest that large scale monitoring of mangrove forests should also consider fragmentation. This work highlights that regional priorities for conservation based on forest loss rates can overlook fragmentation and associated loss of ecosystem functionality.

A conceptual framework to untangle the concept of urban ecosystem services.

Urban ecosystem service (UES) is becoming an influential concept to guide the planning, design, and management of urban landscapes towards urban sustainability. However, its use is hindered by definitional ambiguity, and the conceptual bases underpinning its application remain weak. This is exemplified by two different but equally valid interpretations of UES: "urban ecosystem services", referring to ecosystem services from analogs of natural and semi-natural ecosystems within urban boundaries, and "urban ecosystem services", a much broader term that includes the former group as well as urban services in a city. While we recognize that a single definition of UES is not possible nor necessary as its application is context-dependent, it is nevertheless useful to clarify the relationships between these interpretations to promote consistent use, and importantly, explore how a broader interpretation of UES might advance its applications in areas that have been neglected. We developed a conceptual framework that links UES to natural and human-derived capital to explain the relationships between the dual meanings of UES and proposed three normative propositions to guide its application: (1) integrate holistically multiple components of natural capital to provide UES, (2) reduce dependence on non-renewable abiotic resources and human-derived capital, and (3) enhance UES through technology. The framework we developed helps to resolve the current ambiguity in the meanings of UES, highlights the need to recognise neglected aspects of natural capital important for UES, and can be used to clarify relationships with related concepts conveying dependence of human well-being on nature.

Social media, nature, and life satisfaction: global evidence of the biophilia hypothesis.

Humans may have evolved a need to connect with nature, and nature provides substantial cultural and social values to humans. However, quantifying the connection between humans and nature at a global scale remains challenging. We lack answers to fundamental questions: how do humans experience nature in different contexts (daily routines, fun activities, weddings, honeymoons, other celebrations, and vacations) and how do nature experiences differ across countries? We answer these questions by coupling social media and artificial intelligence using 31,534 social media photographs across 185 countries. We find that nature was more likely to appear in photographs taken during a fun activity, honeymoon, or vacation compared to photographs of daily routines. More importantly, the proportion of photographs with nature taken during fun activities is associated with national life satisfaction scores. This study provides global evidence of the biophilia hypothesis by showing a connection between humans and nature that contributes to life satisfaction and highlights how nature serves as background to many of our positive memories.

Using social media user attributes to understand human-environment interactions at urban parks.

Urban parks and green spaces are among the few places where city dwellers can have regular contact with nature and engage in outdoor recreation. Social media data provide opportunities to understand such human-environment interactions. While studies have demonstrated that geo-located photographs are useful indicators of recreation across different spaces, recreation behaviour also varies between different groups of people. Our study used social media to assess behavioural patterns across different groups of park users in tropical Singapore. 4,674 users were grouped based on the location and content of their photographs on the Flickr platform. We analysed how these groups varied spatially in the parks they visited, as well as in their photography behaviour. Over 250,000 photographs were analysed, including those uploaded and favourited by users, and all photographs taken at city parks. There were significant differences in the number and types of park photographs between tourists and locals, and between user-group axes formed from users' photograph content. Spatial mapping of different user groups showed distinct patterns in the parks they were attracted to. Future work should consider such variability both within and between data sources, to provide a more context-dependent understanding of human-environment interactions and preferences for outdoor recreation.

Serum amyloid P component promotes formation of distinct aggregated lysozyme morphologies and reduces toxicity in Drosophila flies expressing F57I lysozyme.

Many conflicting reports about the involvement of serum amyloid P component (SAP) in amyloid diseases have been presented over the years; SAP is known to be a universal component of amyloid aggregates but it has been suggested that it can both induce and suppress amyloid formation. By using our Drosophila model of systemic lysozyme amyloidosis, SAP has previously been shown to reduce the toxicity induced by the expression of the disease-associated lysozyme variant, F57I, in the Drosophila central nervous system. This study further investigates the involvement of SAP in modulating lysozyme toxicity using histochemistry and spectral analyses on the double transgenic WT and F57I lysozyme flies to probe; i) formation of aggregates, ii) morphological differences of the aggregated lysozyme species formed in the presence or absence of SAP, iii) location of lysozyme and iv) co-localisation of lysozyme and SAP in the fly brain. We found that SAP can counteract the toxicity (measured by the reduction in the median survival time) induced by F57I lysozyme by converting toxic F57I species into less toxic amyloid-like structures, as reflected by the spectral changes that p-FTAA undergoes when bound to lysozyme deposits in F57I-F57I-SAP flies as compared to F57I-F57I flies. Indeed, when SAP was introduced to in vitro lysozyme fibril formation, the endpoint fibrils had enhanced ThT fluorescence intensity as compared to lysozyme fibrils alone. This suggests that a general mechanism for SAP's role in amyloid diseases may be to promote the formation of stable, amyloid-like fibrils, thus decreasing the impact of toxic species formed along the aggregation pathway.

Characterizing Coastal Ecosystem Service Trade-offs with Future Urban Development in a Tropical City.

With rapid urbanization in the coastal zone and increasing habitat losses, it is imperative to understand how urban development affects coastal biodiversity and ecosystem service provision. Furthermore, it is important to understand how habitat fragments can best be incorporated into broader land use planning and coastal management, in order to maximize the environmental benefits they provide. In this study, we characterized the trade-offs between (a) urban development and individual mangrove environmental indicators (habitat quality and ecosystem services), and (b) between different environmental indicators in the tropical nation of Singapore. A range of biological, biophysical, and cultural indicators, including carbon, charcoal production, support for offshore fisheries, recreation, and habitat quality for a threatened species were quantified using field-based, remote sensing, and expert survey methods. The shape of the trade-off Pareto frontiers was analyzed to assess the sensitivity of environmental indicators for development. When traded off individually with urban development, four out of five environmental indicators were insensitive to development, meaning that relatively minor degradation of the indicator occurred while development was below a certain threshold, although indicator loss accelerated once this threshold was reached. Most of the pairwise relationships between the five environmental indicators were synergistic; only carbon storage and charcoal production, and charcoal production and recreational accessibility showed trade-offs. Trade-off analysis and land use optimization using Pareto frontiers could be a useful decision-support tool for understanding how changes in land use and coastal management will impact the ability of ecosystems to provide environmental benefits.

Rates and drivers of mangrove deforestation in Southeast Asia, 2000-2012.

The mangrove forests of Southeast Asia are highly biodiverse and provide multiple ecosystem services upon which millions of people depend. Mangroves enhance fisheries and coastal protection, and store among the highest densities of carbon of any ecosystem globally. Mangrove forests have experienced extensive deforestation owing to global demand for commodities, and previous studies have identified the expansion of aquaculture as largely responsible. The proportional conversion of mangroves to different land use types has not been systematically quantified across Southeast Asia, however, particularly in recent years. In this study we apply a combined geographic information system and remote sensing method to quantify the key proximate drivers (i.e., replacement land uses) of mangrove deforestation in Southeast Asia between 2000 and 2012. Mangrove forests were lost at an average rate of 0.18% per year, which is lower than previously published estimates. In total, more than 100,000 ha of mangroves were removed during the study period, with aquaculture accounting for 30% of this total forest change. The rapid expansion of rice agriculture in Myanmar, and the sustained conversion of mangroves to oil palm plantations in Malaysia and Indonesia, are identified as additional increasing and under-recognized threats to mangrove ecosystems. Our study highlights frontiers of mangrove deforestation in the border states of Myanmar, on Borneo, and in Indonesian Papua. To implement policies that conserve mangrove forests across Southeast Asia, it is essential to consider the national and subnational variation in the land uses that follow deforestation.

Historical and contemporary cultural ecosystem service values in the rapidly urbanizing city state of Singapore.

Cultural ecosystem services are a function of people and place, so may change as a location transitions from rural to urban. Singapore has undergone rapid urbanization after its independence in 1965, with a concomitant decline in natural habitat extent and accessibility. Using coastal mangrove forests as a case study habitat, changing cultural values were explored with a novel array of techniques, including qualitative archival analysis (photographs, oral histories), current sources (publically uploaded social media photographs), and surveys of (a) the general public and (b) visitors to publically accessible mangroves. Cultural value changed through time, with a significant transition from intrinsic, intrapersonal values (spiritual, cultural heritage) to instrumental, interpersonal values (recreation, education). Additionally, cultural value varied between different mangroves depending on their public accessibility, and the evolving degree of human interaction with the ecosystem as urban development occured. Cultural values change as development transitions, though mangroves still play an important cultural role in a heavily urbanized environment.

Predictive systems biology approach to broad-spectrum, host-directed drug target discovery in infectious diseases.

Knowledge of immune system and host-pathogen pathways can inform development of targeted therapies and molecular diagnostics based on a mechanistic understanding of disease pathogenesis and the host response. We investigated the feasibility of rapid target discovery for novel broad-spectrum molecular therapeutics through comprehensive systems biology modeling and analysis of pathogen and host-response pathways and mechanisms. We developed a system to identify and prioritize candidate host targets based on strength of mechanistic evidence characterizing the role of the target in pathogenesis and tractability desiderata that include optimal delivery of new indications through potential repurposing of existing compounds or therapeutics. Empirical validation of predicted targets in cellular and mouse model systems documented an effective target prediction rate of 34%, suggesting that such computational discovery approaches should be part of target discovery efforts in operational clinical or biodefense research initiatives. We describe our target discovery methodology, technical implementation, and experimental results. Our work demonstrates the potential for in silico pathway models to enable rapid, systematic identification and prioritization of novel targets against existing or emerging biological threats, thus accelerating drug discovery and medical countermeasures research.

Genomic responses in mouse models poorly mimic human inflammatory diseases.

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

Global analysis of the meiotic crossover landscape.

Tight control of the number and distribution of crossovers is of great importance for meiosis. Crossovers establish chiasmata, which are physical connections between homologous chromosomes that provide the tension necessary to align chromosomes on the meiotic spindle. Understanding the mechanisms underlying crossover control has been hampered by the difficulty in determining crossover distributions. Here, we present a microarray-based method to analyze multiple aspects of crossover control simultaneously and rapidly, at high resolution, genome-wide, and on a cell-by-cell basis. Using this approach, we show that loss of interference in zip2 and zip4/spo22 mutants is accompanied by a reduction in crossover homeostasis, thus connecting these two levels of crossover control. We also provide evidence to suggest that repression of crossing over at telomeres and centromeres arises from different mechanisms. Lastly, we uncover a surprising role for the synaptonemal complex component Zip1 in repressing crossing over at the centromere.

Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways.

Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for the future of medicine. Patients with injuries severe enough to develop multiple organ dysfunction syndrome have multiple immune derangements, including T cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers an opportunity to discover leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in T cell (5,693 genes), monocyte (2,801 genes), and total leukocyte (3,437 genes) transcriptomes, with only 911 of these genes common to all three cell populations (12%). T cell-specific pathway analyses identified increased gene expression of several inhibitory receptors (PD-1, CD152, NRP-1, and Lag3) and concomitant decreases in stimulatory receptors (CD28, CD4, and IL-2Ralpha). Functional analysis of T cells and monocytes confirmed reduced T cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly enriched cell populations combined with knowledge-based pathway analyses leads to the identification of regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell-specific pathway analyses can be used to discover pathway alterations in human disease.

A network-based analysis of systemic inflammation in humans.

Oligonucleotide and complementary DNA microarrays are being used to subclassify histologically similar tumours, monitor disease progress, and individualize treatment regimens. However, extracting new biological insight from high-throughput genomic studies of human diseases is a challenge, limited by difficulties in recognizing and evaluating relevant biological processes from huge quantities of experimental data. Here we present a structured network knowledge-base approach to analyse genome-wide transcriptional responses in the context of known functional interrelationships among proteins, small molecules and phenotypes. This approach was used to analyse changes in blood leukocyte gene expression patterns in human subjects receiving an inflammatory stimulus (bacterial endotoxin). We explore the known genome-wide interaction network to identify significant functional modules perturbed in response to this stimulus. Our analysis reveals that the human blood leukocyte response to acute systemic inflammation includes the transient dysregulation of leukocyte bioenergetics and modulation of translational machinery. These findings provide insight into the regulation of global leukocyte activities as they relate to innate immune system tolerance and increased susceptibility to infection in humans.

Genetic diversity in yeast assessed with whole-genome oligonucleotide arrays.

The availability of a complete genome sequence allows the detailed study of intraspecies variability. Here we use high-density oligonucleotide arrays to discover 11,115 single-feature polymorphisms (SFPs) existing in one or more of 14 different yeast strains. We use these SFPs to define regions of genetic identity between common laboratory strains of yeast. We assess the genome-wide distribution of genetic variation on the basis of this yeast population. We find that genome variability is biased toward the ends of chromosomes and is more likely to be found in genes with roles in fermentation or in transport. This subtelomeric bias may arise through recombination between nonhomologous sequences because full-gene deletions are more common in these regions than in more central regions of the chromosome.