Kidney function trajectories, associated factors, and outcomes in multiethnic Asian patients with type 2 diabetes.

BACKGROUND: We examined the trajectory of estimated glomerular filtrate rate (eGFR), associated risk factors, and its relationship with end-stage kidney disease (ESKD) among a multiethnic patient population with type 2 diabetes in Singapore. METHODS: A follow-up study included 62 080 individuals with type 2 diabetes aged ≥18 years in a multi-institutional SingHealth Diabetes Registry between 2013 and 2019. eGFR trajectories were analyzed using latent class linear mixed models. Factors associated with eGFR trajectories were evaluated using multinomial logistic regression. The association of eGFR trajectories with ESKD was assessed via competing risk models. RESULTS: Trajectory of kidney function, determined by eGFR, was nonlinear. The trajectory pattern was classified as stable initially then gradual decline (75%), progressive decline (21.9%), and rapid decline (3.1%). Younger age, female sex, Malay ethnicity, lower-income housing type, current smoking, higher glycated hemoglobin, lower low-density lipoprotein, higher triglyceride, uncontrolled blood pressure, albuminuria, cardiovascular disease, hypertension, and higher eGFR levels each were associated with progressive or rapid decline. Compared with the trajectory of stable initially then gradual eGFR decline, progressive decline increased the hazard of ESKD by 6.14-fold (95% confidence interval [CI]: 4.96-7.61)) and rapid decline by 82.55 folds (95% CI: 55.90-121.89). CONCLUSIONS: Three nonlinear trajectory classes of kidney function were identified among multiethnic individuals with type 2 diabetes in Singapore. About one in four individuals had a progressive or rapid decline in eGFR. Our results suggest that eGFR trajectories are correlated with multiple social and modifiable risk factors and inform the risk of ESKD.

Associations between sleep trajectories up to 54 months and cognitive school readiness in 4 year old preschool children.

Purpose: This study explores the association between the duration and variation of infant sleep trajectories and subsequent cognitive school readiness at 48-50 months. Methods: Participants were 288 multi-ethnic children, within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Caregiver-reported total, night and day sleep durations were obtained at 3, 6, 9, 12, 18, 24 using the Brief Infant Sleep Questionnaire and 54 months using the Child Sleep Habits Questionnaire. Total, night and day sleep trajectories with varying durations (short, moderate, or long) and variability (consistent or variable; defined by standard errors) were identified. The cognitive school readiness test battery was administered when the children were between 48 and 50 months old. Both unadjusted adjusted analysis of variance models and adjusted analysis of covariance models (for confounders) were performed to assess associations between sleep trajectories and individual school readiness tests in the domains of language, numeracy, general cognition and memory. Results: In the unadjusted models, children with short variable total sleep trajectories had poorer performance on language tests compared to those with longer and more consistent trajectories. In both unadjusted and adjusted models, children with short variable night sleep trajectories had poorer numeracy knowledge compared to their counterparts with long consistent night sleep trajectories. There were no equivalent associations between sleep trajectories and school readiness performance for tests in the general cognition or memory domains. There were no significant findings for day sleep trajectories. Conclusion: Findings suggest that individual differences in longitudinal sleep duration patterns from as early as 3 months of age may be associated with language and numeracy aspects of school readiness at 48-50 months of age. This is important, as early school readiness, particularly the domains of language and mathematics, is a key predictor of subsequent academic achievement.

Longitudinal HbA1c trajectory modelling reveals the association of HbA1c and risk of hospitalization for heart failure for patients with type 2 diabetes mellitus.

BACKGROUND: Inconsistent conclusions in past studies on the association between poor glycaemic control and the risk of hospitalization for heart failure (HHF) have been reported largely due to the analysis of non-trajectory-based HbA1c values. Trajectory analysis can incorporate the effects of HbA1c variability across time, which may better elucidate its association with macrovascular complications. Furthermore, studies analysing the relationship between HbA1c trajectories from diabetes diagnosis and the occurrence of HHF are scarce. METHODS: This is a prospective cohort study of the SingHealth Diabetes Registry (SDR). 17,389 patients diagnosed with type 2 diabetes mellitus (T2DM) from 2013 to 2016 with clinical records extending to the end of 2019 were included in the latent class growth analysis to extract longitudinal HbA1c trajectories. Association between HbA1c trajectories and risk of first known HHF is quantified with the Cox Proportional Hazards (PH) model. RESULTS: 5 distinct HbA1c trajectories were identified as 1. low stable (36.1%), 2. elevated stable (40.4%), 3. high decreasing (3.5%), 4. high with a sharp decline (10.8%), and 5. moderate decreasing (9.2%) over the study period of 7 years. Poorly controlled HbA1c trajectories (Classes 3, 4, and 5) are associated with a higher risk of HHF. Using the diabetes diagnosis time instead of a commonly used pre-defined study start time or time from recruitment has an impact on HbA1c clustering results. CONCLUSIONS: Findings suggest that tracking the evolution of HbA1c with time has its importance in assessing the HHF risk of T2DM patients, and T2DM diagnosis time as a baseline is strongly recommended in HbA1c trajectory modelling. To the authors' knowledge, this is the first study to identify an association between HbA1c trajectories and HHF occurrence from diabetes diagnosis time.

Trajectories of reported sleep duration associate with early childhood cognitive development.

STUDY OBJECTIVES: Examine how different trajectories of reported sleep duration associate with early childhood cognition. METHODS: Caregiver-reported sleep duration data (n = 330) were collected using the Brief Infant Sleep Questionnaire at 3, 6, 9, 12, 18, and 24 months and Children's Sleep Habits Questionnaire at 54 months. Multiple group-based day-, night-, and/or total sleep trajectories were derived-each differing in duration and variability. Bayley Scales of Infant and Toddler Development-III (Bayley-III) and the Kaufman Brief Intelligence Test- 2 (KBIT-2) were used to assess cognition at 24 and 54 months, respectively. RESULTS: Compared to short variable night sleep trajectory, long consistent night sleep trajectory was associated with higher scores on Bayley-III (cognition and language), while moderate/long consistent night sleep trajectories were associated with higher KBIT-2 (verbal and composite) scores. Children with a long consistent total sleep trajectory had higher Bayley-III (cognition and expressive language) and KBIT-2 (verbal and composite) scores compared to children with a short variable total sleep trajectory. Moderate consistent total sleep trajectory was associated with higher Bayley-III language and KBIT-2 verbal scores relative to the short variable total trajectory. Children with a long variable day sleep had lower Bayley-III (cognition and fine motor) and KBIT-2 (verbal and composite) scores compared to children with a short consistent day sleep trajectory. CONCLUSIONS: Longer and more consistent night- and total sleep trajectories, and a short day sleep trajectory in early childhood were associated with better cognition at 2 and 4.5 years.

Geographical clusters of dengue outbreak in Singapore during the Covid-19 nationwide lockdown of 2020.

Dengue, a mosquito-transmitted viral disease, has posed a public health challenge to Singaporean residents over the years. In 2020, Singapore experienced an unprecedented dengue outbreak. We collected a dataset of geographical dengue clusters reported by the National Environment Agency (NEA) from 15 February to 9 July in 2020, covering the nationwide lockdown associated with Covid-19 during the period from 7 April to 1 June. NEA regularly updates the dengue clusters during which an infected person may be tagged to one cluster based on the most probable infection location (residential apartment or workplace address), which is further matched to fine-grained spatial units with an average coverage of about 1.35 km2. Such dengue cluster dataset helps not only reveal the dengue transmission patterns, but also reflect the effects of lockdown on dengue spreading dynamics. The resulting data records are released in simple formats for easy access to facilitate studies on dengue epidemics.

Energy, environmental, economic and social equity (4E) pressures of COVID-19 vaccination mismanagement: A global perspective.

Vaccination now offers a way to resolve the COVID-19 pandemic. However, it is critical to recognise the full energy, environmental, economic and social equity (4E) impacts of the vaccination life cycle. The full 4E impacts include the design and trials, order management, material preparation, manufacturing, cold chain logistics, low-temperature storage, crowd management and end-of-life waste management. A life cycle perspective is necessary for sustainable vaccination management because a prolonged immunisation campaign for COVID-19 is likely. The impacts are geographically dispersed across sectors and regions, creating real and virtual 4E footprints that occur at different timescales. Decision-makers in industry and governments have to act, unify, resolve, and work together to implement more sustainable COVID-19 vaccination management globally and locally to minimise the 4E footprints. Potential practices include using renewable energy in production, storage, transportation and waste treatment, using better product design for packaging, using the Internet of Things (IoT) and big data analytics for better logistics, using real-time database management for better tracking of deliveries and public vaccination programmes, and using coordination platforms for more equitable vaccine access. These practices raise global challenges but suggest solutions with a 4E perspective, which could mitigate the impacts of global vaccination campaigns and prepare sustainably for future pandemics and global warming.

More Is Not Enough: A Deeper Understanding of the COVID-19 Impacts on Healthcare, Energy and Environment Is Crucial.

The coronavirus disease 2019 (COVID-19) pandemic has magnified the insufficient readiness of humans in dealing with such an unexpected occurrence. During the pandemic, sustainable development goals have been hindered severely. Various observations and lessons have been highlighted to emphasise local impacts on a single region or single sector, whilst the holistic and coupling impacts are rarely investigated. This study overviews the structural changes and spatial heterogeneities of changes in healthcare, energy and environment, and offers perspectives for the in-depth understanding of the COVID-19 impacts on the three sectors, in particular the cross-sections of them. Practical observations are summarised through the broad overview. A novel concept of the healthcare-energy-environment nexus under climate change constraints is proposed and discussed, to illustrate the relationships amongst the three sectors and further analyse the dynamics of the attention to healthcare, energy and environment in view of decision-makers. The society is still on the way to understanding the impacts of the whole episode of COVID-19 on healthcare, energy, environment and beyond. The raised nexus thinking could contribute to understanding the complicated COVID-19 impacts and guiding sustainable future planning.

Spatial-temporal potential exposure risk analytics and urban sustainability impacts related to COVID-19 mitigation: A perspective from car mobility behaviour.

Coronavirus disease-2019 (COVID-19) poses a significant threat to the population and urban sustainability worldwide. The surge mitigation is complicated and associates many factors, including the pandemic status, policy, socioeconomics and resident behaviours. Modelling and analytics with spatial-temporal big urban data are required to assist the mitigation of the pandemic. This study proposes a novel perspective to analyse the spatial-temporal potential exposure risk of residents by capturing human behaviours based on spatial-temporal car park availability data. Near real-time data from 1,904 residential car parks in Singapore, a classical megacity, are collected to analyse car mobility and its spatial-temporal heat map. The implementation of the circuit breaker, a COVID-19 measure, in Singapore has reduced the mobility and heat (daily frequency of mobility) significantly at about 30.0%. It contributes to a 44.3%-55.4% reduction in the transportation-related air emissions under two scenarios of travelling distance reductions. Urban sustainability impacts in both environment and economy are discussed. The spatial-temporal potential exposure risk mapping with space-time interactions is further investigated via an extended Bayesian spatial-temporal regression model. The maximal reduction rate of the defined potential exposure risk lowers to 37.6% by comparison with its peak value. The big data analytics of changes in car mobility behaviour and the resultant potential exposure risks can provide insights to assist in (a) designing a flexible circuit breaker exit strategy, (b) precise management via identifying and tracing hotspots on the mobility heat map, and (c) making timely decisions by fitting curves dynamically in different phases of COVID-19 mitigation. The proposed method has the potential to be used by decision-makers worldwide with available data to make flexible regulations and planning.

Variations in longitudinal sleep duration trajectories from infancy to early childhood.

OBJECTIVE: This study investigates variations in night, day, and total sleep trajectories across infancy and childhood in Asian children. PARTICIPANTS: Participants consisted of a subset of 901 children, within the Growing Up in Singapore Towards healthy Outcomes cohort, which recruited 1247 pregnant women between June 2009 and September 2010. DESIGN: We used a novel conditional probabilistic trajectory model: a probabilistic model for mixture distribution, allowing different trajectory curves and model variances among groups to cluster longitudinal observations. Longitudinal sleep duration data for the trajectory analyses were collected from caregiver-reported questionnaires at 3, 6, 9, 12, 18, 24, and 54 months. RESULTS: We found 3 patterns of night sleep trajectories (n = 356): long consistent (31%), moderate consistent (41%), and short variable (28%); and 4 patterns of day sleep trajectories (n = 347): long variable (21%), long consistent (20%), moderate consistent (34%), and short consistent (25%). We also identified 4 patterns of total sleep trajectories (n = 345): long variable (19%), long consistent (26%), moderate consistent (28%), and short variable (27%). Short, moderate, and long trajectories differed significantly in duration. Children with consistent trajectories also displayed sleep patterns that were significantly more representative of typical developmental sleep patterns than children with variable trajectories. CONCLUSIONS: This is the first study to describe multiple sleep trajectories in Singaporean children and identify between-individual variability within the trajectory groups. Compared to predominantly Caucasian samples, night/total sleep trajectories were generally shorter, while day sleep trajectories were longer. Future studies should investigate how these variations are linked to different developmental outcomes.

Early dengue outbreak detection modeling based on dengue incidences in Singapore during 2012 to 2017.

Dengue has been as an endemic with year-round presence in Singapore. In the recent years 2013, 2014, and 2016, there were several severe dengue outbreaks, posing serious threat to the public health. To proactively control and mitigate the disease spread, early warnings of dengue outbreaks, at which there are rapid and large-scale spread of dengue incidences, are extremely helpful. In this study, a two-step framework is proposed to predict dengue outbreaks and it is evaluated based on the dengue incidences in Singapore during 2012 to 2017. First, a generalized additive model (GAM) is trained based on the weekly dengue incidence data during 2006 to 2011. The proposed GAM is a one-week-ahead forecasting model, and it inherently accounts for the possible correlation among the historical incidence data, making the residuals approximately normally distributed. Then, an exponentially weighted moving average (EWMA) control chart is proposed to sequentially monitor the weekly residuals during 2012 to 2017. Our investigation shows that the proposed two-step framework is able to give persistent signals at the early stage of the outbreaks in 2013, 2014, and 2016, which provides early alerts of outbreaks and wins time for the early interventions and the preparation of necessary public health resources. In addition, extensive simulations show that the proposed method is comparable to other potential outbreak detection methods and it is robust to the underlying data-generating mechanisms.

Statistical modeling reveals the effect of absolute humidity on dengue in Singapore.

Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM) was used to evaluate and compare the impact of weekly Absolute Humidity (AH) and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed) on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT) also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing factors into consideration in order to make meaningful public policy recommendations.

Comparability of results from pair and classical model formulations for different sexually transmitted infections.

The "classical model" for sexually transmitted infections treats partnerships as instantaneous events summarized by partner change rates, while individual-based and pair models explicitly account for time within partnerships and gaps between partnerships. We compared predictions from the classical and pair models over a range of partnership and gap combinations. While the former predicted similar or marginally higher prevalence at the shortest partnership lengths, the latter predicted self-sustaining transmission for gonorrhoea (GC) and Chlamydia (CT) over much broader partnership and gap combinations. Predictions on the critical level of condom use (C(c)) required to prevent transmission also differed substantially when using the same parameters. When calibrated to give the same disease prevalence as the pair model by adjusting the infectious duration for GC and CT, and by adjusting transmission probabilities for HIV, the classical model then predicted much higher C(c) values for GC and CT, while C(c) predictions for HIV were fairly close. In conclusion, the two approaches give different predictions over potentially important combinations of partnership and gap lengths. Assuming that it is more correct to explicitly model partnerships and gaps, then pair or individual-based models may be needed for GC and CT since model calibration does not resolve the differences.

Evaluating temporal factors in combined interventions of workforce shift and school closure for mitigating the spread of influenza.

BACKGROUND: It is believed that combined interventions may be more effective than individual interventions in mitigating epidemic. However there is a lack of quantitative studies on performance of the combination of individual interventions under different temporal settings. METHODOLOGY/PRINCIPAL FINDINGS: To better understand the problem, we develop an individual-based simulation model running on top of contact networks based on real-life contact data in Singapore. We model and evaluate the spread of influenza epidemic with intervention strategies of workforce shift and its combination with school closure, and examine the impacts of temporal factors, namely the trigger threshold and the duration of an intervention. By comparing simulation results for intervention scenarios with different temporal factors, we find that combined interventions do not always outperform individual interventions and are more effective only when the duration is longer than 6 weeks or school closure is triggered at the 5% threshold; combined interventions may be more effective if school closure starts first when the duration is less than 4 weeks or workforce shift starts first when the duration is longer than 4 weeks. CONCLUSIONS/SIGNIFICANCE: We therefore conclude that identifying the appropriate timing configuration is crucial for achieving optimal or near optimal performance in mitigating the spread of influenza epidemic. The results of this study are useful to policy makers in deliberating and planning individual and combined interventions.

Temporal factors in school closure policy for mitigating the spread of influenza.

Is school closure effective in mitigating influenza outbreaks? For Singapore, we developed an individual-based simulation model using real-life contact data. We evaluated the impacts of temporal factors - trigger threshold and duration - on the effectiveness of school closure as a mitigation policy. We found an upper bound of the duration of school closure, where further extension beyond which will not bring additional benefits to suppressing the attack rate and peak incidence. For school closure with a relatively short duration (< 6 weeks), it is more effective to start closure after a relatively longer delay from the first day of infection; if the duration of school closure is long (>6 weeks), however, it is better to start it as early as reasonable. Our studies reveal the critical importance of timing in school closure, especially in cost-cautious situations. Our studies also demonstrate the great potential of a properly developed individual-based simulation model in evaluating various disease control policies.

A noisy chaotic neural network for solving combinatorial optimization problems: stochastic chaotic simulated annealing.

Recently Chen and Aihara have demonstrated both experimentally and mathematically that their chaotic simulated annealing (CSA) has better search ability for solving combinatorial optimization problems compared to both the Hopfield-Tank approach and stochastic simulated annealing (SSA). However, CSA may not find a globally optimal solution no matter how slowly annealing is carried out, because the chaotic dynamics are completely deterministic. In contrast, SSA tends to settle down to a global optimum if the temperature is reduced sufficiently slowly. Here we combine the best features of both SSA and CSA, thereby proposing a new approach for solving optimization problems, i.e., stochastic chaotic simulated annealing, by using a noisy chaotic neural network. We show the effectiveness of this new approach with two difficult combinatorial optimization problems, i.e., a traveling salesman problem and a channel assignment problem for cellular mobile communications.

Data dimensionality reduction with application to simplifying RBF network structure and improving classification performance.

For high dimensional data, if no preprocessing is carried out before inputting patterns to classifiers, the computation required may be too heavy. For example, the number of hidden units of a radial basis function (RBF) neural network can be too large. This is not suitable for some practical applications due to speed and memory constraints. In many cases, some attributes are not relevant to concepts in the data at all. In this paper, we propose a novel separability-correlation measure (SCM) to rank the importance of attributes. According to the attribute ranking results, different attribute subsets are used as inputs to a classifier, such as an RBF neural network. Those attributes that increase the validation error are deemed irrelevant and are deleted. The complexity of the classifier can thus be reduced and its classification performance improved. Computer simulations show that our method for attribute importance ranking leads to smaller attribute subsets with higher accuracies compared with the existing SUD and Relief-F methods. We also propose a modified method for efficient construction of an RBF classifier. In this method we allow for large overlaps between clusters corresponding to the same class label. Our approach significantly reduces the structural complexity of the RBF network and improves the classification performance.