Quantifying spatial heterogeneity of vulnerability to short-term PM2.5 exposure with data fusion framework.

The current estimations of the burden of disease (BD) of PM2.5 exposure is still potentially biased by two factors: ignorance of heterogeneous vulnerabilities at diverse urbanization levels and reliance on the risk estimates from existing literature, usually from different locations. Our objectives are (1) to build up a data fusion framework to estimate the burden of PM2.5 exposure while evaluating local risks simultaneously and (2) to quantify their spatial heterogeneity, relationship to land-use characteristics, and derived uncertainties when calculating the disease burdens. The feature of this study is applying six local databases to extract PM2.5 exposure risk and the BD information, including the risks of death, cardiovascular disease (CVD), and respiratory disease (RD), and their spatial heterogeneities through our data fusion framework. We applied the developed framework to Tainan City in Taiwan as a use case estimated the risks by using 2006-2016 emergency department visit data, air quality monitoring data, and land-use characteristics and further estimated the BD caused by daily PM2.5 exposure in 2013. Our results found that the risks of CVD and RD in highly urbanized areas and death in rural areas could reach 1.20-1.57 times higher than average. Furthermore, we performed a sensitivity analysis to assess the uncertainty of BD estimations from utilizing different data sources, and the results showed that the uncertainty of the BD estimations could be contributed by different PM2.5 exposure data (20-32%) and risk values (0-86%), especially for highly urbanized areas. In conclusion, our approach for estimating BD based on local databases has the potential to be generalized to the developing and overpopulated countries and to support local air quality and health management plans.

Application of a health index using PM2.5 concentration reductions for evaluating cross-administrative region air quality policies.

The primary goal of air quality policies is to reduce the impact of air pollution on human health, in particular, it is very important in the attainment-closing geographic areas with densely populated like Taiwan. Air quality policies in general only consider the reduction of emission as well as concentration, in order to highlight the effects of air pollution reduction responded on human health, a health index using PM2.5 concentration reductions (HI-cr) was adopted to evaluate air quality policies in this study. To investigate priorities of cross-administrative region air quality policies, the HI-cr were calculated by using annual results of atmospheric modeling and air quality modeling, which involved the meteorological effect and spatial distribution of air pollution. By studying the emission reduction targets of three administrative regions, Taichung, Changhwa, and Nantau in the Central Taiwan, 8 reduction scenarios were designed and examined. It is found that HI-cr can present detailed information in human health.From the results of adaptability assessement based on health, the equal reduction of emission in present air quality policy gave the most concentration reduction area with lower HI-cr. But according to the analysis in different proportion of emission reduction scenarios, it found that emission reduced more in the most population region, even the concentration reduction is not the highest but HI-cr increased. According to the analysis of different emission reduction policies, this study suggests HI-cr is an important index to evaluate the air pollution control policies instead of considering the impact of air pollutant concentrations only, especially in cross-administrative regions.Implications: In this study, we present a modified health index, HI-cr, to determine the priority of cross-administrative air quality policies using PM2.5 concentration reduction. HI-cr is adaptable for any types of geography, in particular for areas where the air quality is almost attainment like Taiwan. Cross-administrative air quality policies could be evaluated using HI-cr, it could highlight the high performance on population health improvement rather than high concentration reduction. In particular, for economies where the air quality is almost attainment and with complex terrain and dense population, air quality policies should consider the health prevention issues.

Transient risk of ambient fine particulate matter on hourly cardiovascular events in Tainan City, Taiwan.

BACKGROUND: The association between daily changes in ambient fine particulate matter (PM2.5) and cardiovascular diseases have been well established in mechanistic, epidemiologic and exposure studies. Only a few studies examined the effect of hourly variations in air pollution on triggering cardiovascular events. Whether the current PM2.5 standards can protect vulnerable individuals with chronic cardiovascular diseases remain uncertain. METHODS: we conducted a time-stratified, case-crossover study to assess the associations between hourly changes in PM2.5 levels and the vascular disease onset in residents of Tainan City, Taiwan, visiting Emergency Room of Chi Mei Medical Center between January 2006 and December 2016. There were 26,749 cases including 10,310 females (38.5%) and 16,439 males (61.5%) identified. The time of emergency visit was identified as the onset for each case and control cases were selected as the same times on other days, on the same day of the week in the same month and year respectively. Residential address was used to identify the ambient air pollution exposure concentrations from the closest station. Conditional logistic regression with the stepwise selection method was used to estimate adjusted odds ratios (ORs) for the association. RESULTS: When we only included cases occurring at PM2.5>10 µg/m3 and PM2.5>25 µg/m3, very significant ORs could be observed for 10 µg/m3 increases in PM2.5 at 0 and 1 hour, implying fine particulate exposure could promptly trigger vascular disease events. Moreover, a very clear increase in risk could be observed with cumulative exposure from 0 to 48 hours, especially in those cases where PM2.5>25 µg/m3. CONCLUSIONS: Our study demonstrated that transient and low concentrations of ambient PM2.5 trigger adult vascular disease events, especially cerebrovascular disease, regardless of age, sex, and exposure timing. Warning and delivery systems should be setup to protect people from these prompt adverse health impacts.

Difference of performance in response to disease admissions between daily time air quality indices and those derived from average and entropy functions.

Daily time air quality indices, which can reflect air quality in 1 day, are suitable for identifying daily exposure during conditions of poor air quality. The aim of this study is to compare the main effectiveness of four daily time indices in representing variation in the number of disease admissions. These indices include pollution standard index (PSI), air quality index (AQI) and their respective indices derived from mean and entropy functions: MEPSI and MEAQI. The hourly concentrations of fine particulate matter less than 10 µm in diameter (PM10), PM2.5, O3, CO, NO2 and SO2 from 1 January 2006 to 31 December 2010 were obtained from 14 air quality monitoring stations owned by the Environmental Protection Administration (EPA) in the Kaoping region, Taiwan.Instead of circulatory system disease admissions, the indices were correlative with the number of respiratory disease admissions with correlative coefficients of 0.49 to 0.56 (P < 0.05). The daily time air quality indices derived from mean and entropy functions improved their performance of reactive range and air pollution identification. The reactive range of MEPSI and MEAQI was 1.4-3 times that of the original indices. The MEPSI and MEAQI increased identification from 40 to 180 in index scale and revealed one to two additional categories of public health effect information. In comparison with other indices, MEAQI is more effective for application to pollution events with multiple air pollutants.

Public health risks of prolonged fine particle events associated with stagnation and air quality index based on fine particle matter with a diameter <2.5 µm in the Kaoping region of Taiwan.

The increasing frequency of droughts in tropical and sub-tropical areas since 1970 due to climate change requires a better understanding of the relationship between public health and long-duration fine particle events (FPE; defined as a day with an average PM2.5 ≥ 35.5 µg/m3) associated with rainfall and wind speed. In the Kaoping region of Taiwan, 94.46 % of the daily average PM2.5 in winter exceeds the limit established by 2005 World Health Organization (WHO) guidelines. This study investigated the differences in winter weather characteristics and health effects between non-FPE and FPE days, and the performance of air quality indexes on FPE days. Z-statistics for one-tailed tests, multiplicative decomposition models, logarithmic regression, and product-moment correlations were used for the analysis. The results indicate that mean wind speeds, rainfall hours, and air temperature were significantly decreased on FPE days. Daily mean PM2.5 concentrations were positively correlated to the duration of FPE days. The duration of FPE days was positively related to the length of drought (r = 0.97, P < 0.05). The number of respiratory admissions was positively correlated with the FPE duration (r 2 = 0.60). The age groups >15 years experienced the largest average reduction in asthma admissions on lag-days. Compared to the pollutant standard index (PSI) and revised air quality index (RAQI), the PM2.5 index is more representative and sensitive to changes in PM2.5 concentrations.

Relationship between fine particulate matter events with respect to synoptic weather patterns and the implications for circulatory and respiratory disease in Taipei, Taiwan.

The aim of the study is to assess the relationship between PM2.5, synoptic weather patterns, and admissions for circulatory and respiratory disease. A PM2.5 event is defined as a day when the daily mean PM2.5 concentration exceeds 65 µg/m(3). PM2.5 events that coincided with the occurrence of PM attributed to Asian dust storm (ADS) and photochemical smog (PCS) were removed from the study in order to focus solely on the health effects from PM2.5. A one-tailed z-test and a relative risk (RR) estimate were performed. Hospital admissions for respiratory diseases were greater than those for circulatory diseases, and asthma-related diseases had a higher impact in the Adults group, and the maximum RR was 1.94 [1.37 2.77] on the first day after the event. It is evident that PM2.5 episodes connected to particular synoptic weather patterns pose a risk to health as large as ADS and PCS events.

The relationship between typhoons' peripheral circulation and ground-level ozone concentrations in central Taiwan.

Surface data of meteorological parameters (wind speed, wind direction, and mixing height) and air pollutant concentrations (O3, NO, and NO2) were collected for a 92-day period associated with typhoon formation in 2005. The influence of typhoons on O3 concentration were defined by azimuth and distance from Taiwan, and Types A, B, and C correspond to typhoons less than 1,500 km from Taiwan and located between azimuths 45° and 135°, 135° and 225°, and 225° and 45°, respectively. Type D corresponds to typhoons more than 1,500 km from Taiwan. Titration reactions were conducted at three temporal phases: 2000-0700, 0800-1100, and 1200-1400 LST (Local Standard Time). The air pollution model (TAPM) was used to simulate wind fields and trajectories of air masses. It was determined that typhoon position affected O3 concentration, temporal and spatial patterns of O3 titration and vertical meteorological characteristics, which were not all at the statistically significant level.

Effect of photochemical smog associated with synoptic weather patterns on cardiovascular and respiratory hospital admissions in metropolitan Taipei.

This study focuses on the relationship between photochemical smog (PS) (hourly ozone conc. >100 ppb), PS-related diseases, and the synoptic weather patterns during 2005-2009 in metropolitan Taipei. The results show that compared to respiratory ailments (ICD code 460-519) and asthma (ICD code 493), cardiovascular ailments (ICD code 390-459) were more clearly influenced by PS events. On the PS event day, the number of admissions of babies, children, and adults increased by 0.04 [95% CI 0.01-0.06], 0.03 [95% CI 0.00-0.07], and 1.12 [95% CI 0.36-1.89] (P < 0.05), respectively. The investigation showed that more than 70% of the PS events were associated primarily with the peripheral circulation of typhoons, Pacific pressure, and discrete Pacific pressure. PS events are a threat to public health. To avoid the ill effects of air pollution, residents should be informed about the daily weather patterns and air quality.

Influence of environmental conditions on asynchronous outbreaks of dengue disease and increasing vector population in Kaohsiung, Taiwan.

The objective of this study was to clarify the associations between dengue vectors and the number of dengue fever admissions. We statistically analyzed the daily meteorological and sea surface temperature (SST) data obtained from 13 monitoring stations for 2002-2007, the daily number of dengue fever admissions to hospitals, as well as the Breteau index (BI) values obtained from the Taiwan Centres for Disease Control for the 38 political districts of metropolitan Kaohsiung. It was found that hot and wet environmental conditions were caused by warm SSTs together with the weather patterns that cause typhoons and high-pressure areas in the tropical Pacific Ocean. The conditions clearly contribute to an increase in the BI. Synoptic weather patterns still remain an important factor in determining the growth of dengue vectors, particularly in rural areas, although public health programs and improved environmental sanitation can also reduce the threat of the disease.

Biochemical characterizations of Escherichia coli-expressed protective antigen Ag473 of Neisseria meningitides group B.

Polysaccharide-based vaccines against Neisseria meningitidis (Nm) serogroups A, C, Y and W135 have been available since 1970, but similar vaccine candidates developed for Nm group B (NmB) have not been successful due to both poor immunogenicity and their potential immunological cross-reactivity with human neurological tissue. In previous reports, a protective antigen and vaccine candidate, Ag473, was identified using proteomics and NmB-specific bactericidal monoclonal antibody. To initiate human phase one clinical trials, antigen production and characterization, pre-clinical toxicology and animal studies are required. In the present study, we report the biochemical characterization of Escherichia coli-expressed recombinant Ag473 (rAg473). Using MALDI-TOF mass analysis, chromatographically purified rAg473 was found to have two major isoforms that have molecular masses of 11,306 and 11,544amu, respectively. The isoforms were separated using RP-HPLC and pooled into two fractions. Based on the chromatogram, the ratio of lipoproteins in fractions #1 and #2 was found to be 1-2. GC-MS analysis of lipoproteins was performed, and the acylated fatty acids were identified. The results indicated that the first lipoproteins in fraction #1 contained the lipids palmitic acid (C16:0), cyclopropaneoctanoic acid (C17:1) and, predominately, stearic acid (C18:0). A different lipid composition of cyclopropaneoctanoic acid (C17:1), oleic acid (C18:1) and, predominately, palmitic acid (C16:0) was found in the second lipoprotein fraction. Both lipoprotein isoforms were tested and found to have Toll-like receptor (TLR) agonist activity in stimulating cytokine secretion from THP-1 cells. Circular dichroism (CD) analysis showed the secondary structure of rAg473 to be dominated by α-helices (48%), and the overall protein structure was stable up to 60°C and could refold after having been exposed to a temperature cycle from 20 to 90°C. In addition, the solubility of rAg473 (5mg/mL) was not affected after several freeze-thaw cycles. These biophysical and immunological properties make rAg473 a good vaccine candidate against NmB.

Urban heat island and air pollution--an emerging role for hospital respiratory admissions in an urban area.

The aim of the study discussed here was to determine the associations among the urban heat island (UHI), air quality, and hospital respiratory admissions in the warm center of an urban area. The authors collected and analyzed the data regarding air quality parameters, meteorological parameters, and the daily hospital respiratory admissions in the Taichung metropolis in the autumns of 2003 and 2004. By collecting the vertical meteorological parameters and air pollutant concentrations via the tethersonde balloon technique, the authors simulated convergence in Dali using The Air Pollution Model (TAPM) for the atmospheric conditions. The authors also examined the hypotheses with Duncan's Multiple Range test, and analyzed spatial patterns vis-à-vis air temperature, air quality, and hospital respiratory admissions with GIS. The results indicated that the UHI phenomenon-which generates convergence and then transports air pollutants to a metropolitan area-increases hospital respiratory admissions in the warm center of an urban area.

Air quality influenced by urban heat island coupled with synoptic weather patterns.

Few studies have discussed the association between the urban heat island (UHI) phenomenon and air quality under synoptic weather patterns conducive to UHI. In this study, the authors used statistical analyses to study this association in the Taichung metropolis region. The air quality data obtained from government-owned observation stations and wind field profiles obtained from tethersonde monitoring (performed during 21-29 October 2004) were combined with the simulations of the horizontal wind fields at different heights by the air pollution model (TAPM). The results show that certain specific synoptic weather patterns worsen the air quality and induce the UHI phenomenon: Taichung's UHI appears clearly under the synoptic weather patterns featuring light air or breezes (0.56 m/s < or =wind speed <2.2 m/s) mainly from the north and west. Furthermore, under these weather patterns, the concentrations of air pollutants (NO2, CO2 and CO) increase significantly (P<0.05) with the UHI intensity. The convergence usually associated with nocturnal UHI causes the accumulation of O3 precursors, as well as other air pollutants, thereby worsening the air quality at that time and also during the following daytime period.

A novel technology for the production of a heterologous lipoprotein immunogen in high yield has implications for the field of vaccine design.

We have developed a novel platform technology that can express high levels of recombinant lipoproteins with intrinsic adjuvant properties. In this study, Ag473 (a lipoprotein from Neisseria meningitidis) can be produced in high yields using Escherichia coli strain C43 (DE3). After testing a non-lipoimmunogen (E3, from dengue virus) fused with different lipid signal peptides from other lipoproteins as well as Ag473 fragments of different lengths, we identified that the fusion sequence has to contain at least the N-terminal 40 residues, D1, of Ag473 to achieve high expression levels of the recombinant lipo-immunogen (rlipo-D1E3). The rlipo-D1E3 was found to elicit stronger anti-E3 and virus neutralizing antibody responses in animal studies than those from rE3 alone or rE3 formulated with alum adjuvant. These results have successfully demonstrated the merit of lipo-immunogens for novel vaccine development.

A novel dengue vaccine candidate that induces cross-neutralizing antibodies and memory immunity.

A novel dengue vaccine candidate comprised of a consensus dengue virus envelope protein domain III (cED III) was developed to fight against dengue virus infection. The amino acid sequence of this novel cED III was obtained by alignment of amino acid sequences from different isolates of the four serotypes of dengue viruses. A proof-of-concept study demonstrated that BALB/c mice immunized with the recombinant cED III developed neutralizing antibodies against all serotypes of dengue virus. Moreover, formulation of recombinant cED III with aluminum phosphate could induce long-lasting antibody responses and anamnestic neutralizing antibody responses following challenge with dengue virus at week 28 after priming. These results demonstrate the possibility of developing a single tetravalent vaccine against dengue viral infections.

The impact of air quality on respiratory admissions during Asian dust storm periods.

The objective of this study was to assess the temporal and spatial patterns of air quality during Asian dust storm (ADS) events between 2000 and 2004, as well as their correlation with the frequency of respiratory admissions in the clinics and hospitals of metropolitan Taipei, Taiwan. The daily air pollutant concentrations and the respiratory admissions on the "index days" were compared with those on the "comparison days". A Geographical Information System (GIS) was used to map the distributions of the air pollutant concentrations and the respiratory admissions. The results showed that short duration ADS events caused a larger Revised Air Quality Index (RAQI) than the long duration ADS events. PM10 and O3 concentrations significantly increased on the first two days of ADS events. The areas showing significant increases in respiratory admissions did not match well with the areas with the most significant air quality deterioration.

Microfluidic chip of fast DNA hybridization using denaturing and motion of nucleic acids.

This study presents the effect of fluidic temperatures and velocities on improving DNA hybridization. The efficiency of hybridization could be improved by introducing elevated temperature in the hot region and velocity in the cold region. Compared with the conventional methods, this hybridization microchip was able to increase the hybridization signal 4.6-fold within 30 min. The 1.4-kb single-stranded target DNA was tested. The increasing tendency of the fluorescence intensity was apparent when the temperature was higher than 82 degrees C, and the fluorescence intensity reached an asymptotic value at T>90 degrees C. A mathematical model was proposed to relate the fluorescence intensity of DNA hybridization with the hot-region temperature and the cold-region velocity. Based on these results, the new hybridization chip with the processes of temperature and velocity differences will improve efficiency of DNA detection. The microchip combined with hot-region temperature and cold-region bulk flow velocity effects could provide additional efficiency in DNA hybridization.

POWER: PhylOgenetic WEb Repeater--an integrated and user-optimized framework for biomolecular phylogenetic analysis.

POWER, the PhylOgenetic WEb Repeater, is a web-based service designed to perform user-friendly pipeline phylogenetic analysis. POWER uses an open-source LAMP structure and infers genetic distances and phylogenetic relationships using well-established algorithms (ClustalW and PHYLIP). POWER incorporates a novel tree builder based on the GD library to generate a high-quality tree topology according to the calculated result. POWER accepts either raw sequences in FASTA format or user-uploaded alignment output files. Through a user-friendly web interface, users can sketch a tree effortlessly in multiple steps. After a tree has been generated, users can freely set and modify parameters, select tree building algorithms, refine sequence alignments or edit the tree topology. All the information related to input sequences and the processing history is logged and downloadable for the user's reference. Furthermore, iterative tree construction can be performed by adding sequences to, or removing them from, a previously submitted job. POWER is accessible at http://power.nhri.org.tw.