Relationships among green space, ambient fine particulate matter, and cancer incidence in Taiwan: A 16-year retrospective cohort study.

INTRODUCTION: Green space and air pollution have been recognized as vital health determinants. There is a paucity of studies examining the interplay between green space, fine particulate matter (PM2.5), and the incidence of specific cancers. OBJECTIVE: We aimed to explore the contributions of green space and ambient PM2.5 to the risk of specific cancers in terms of the most common cancers based on incidence or mortality rate in Taiwan and to ascertain the interaction between green space and PM2.5 and their role in cancer risk. MATERIALS AND METHODS: This retrospective longitudinal cohort study included 407,415 participants. Data were obtained from the 2000-2015 Mei Jau Health Examination Database linked to the Taiwan Cancer Registry and Causes of Death datasets. All participants were aged ≥20 years and had no history of cancer. The environmental exposure were the normalized difference vegetation index (NDVI) and the 2-year average PM2.5 at baseline. Multivariate adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. We adjusted for covariates including demographics, anthropometrics, comorbidities, health behaviors, biochemical data, and environmental factors. RESULTS: During a median follow-up of 10.37 years, 11,576 cancer cases were reported. PM2.5 exposure increased the risk of all cancers (HR: 1.11, [95% CI: 1.06-1.15]), stomach cancer (HR: 1.27, [1.02-1.58]), endocrine gland cancer (HR: 2.13, [1.39-3.26]), breast cancer (HR: 1.12, [1.03-1.22]), and lung cancer (HR: 1.12, [1.01-1.24]). An increase in NDVI reduced the risk of prostate cancer (HR: 0.93, [0.88-0.99]) and lung cancer (HR: 0.95, [0.91-0.99]). NDVI influenced the incidence of prostate and all cancers by reducing PM2.5 concentrations. CONCLUSION: Long-term PM2.5 exposure is associated with an increased risk of some types of cancers. In contrast, an increase in environmental green space exposure is associated with lowering of the risk of prostate and lung cancer.

Long-Term Exposure to Ambient Fine Particulate Matter and Chronic Kidney Disease: A Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) is a serious global public health challenge, but there is limited information on the connection between air pollution and risk of CKD. OBJECTIVE: The aim of this study was to investigate the association between long-term exposure to particulate matter (PM) with an aerodynamic diameter of less than [Formula: see text] ([Formula: see text]) and the development of CKD in a large cohort. METHODS: A total of 100,629 nonCKD Taiwanese residents age 20 y or above were included in this study between 2001 and 2014. Ambient [Formula: see text] concentration was estimated at each participant's address using a satellite-based spatiotemporal model. Incident CKD cases were identified by an estimated glomerular filtration rate (eGFR) of less than [Formula: see text]. We collected information on a wide range of potential confounders/modifiers during the medical examinations. Cox proportional hazard regression was applied to calculate hazard ratios (HRs). RESULTS: During the follow-up, 4,046 incident CKD cases were identified, and the incidence rate was 6.24 per 1,000 person-years. In contrast with participants with the first quintile exposure of [Formula: see text], participants with the fourth and fifth quintiles exposure of [Formula: see text] had increased risk of CKD development, adjusting for age, sex, educational level, smoking, drinking, body mass index, systolic blood pressure, fasting glucose, total cholesterol, and self-reported heart disease or stroke, with an HR [95% confidence interval (CI)] of 1.11 (1.02, 1.22) and 1.15 (1.05, 1.26), respectively. A significant concentration-response trend was observed ([Formula: see text]). Every [Formula: see text] increment in the [Formula: see text] concentration was associated with a 6% higher risk of developing CKD (HR: 1.06, 95% CI: 1.02, 1.10). Sensitivity and stratified analyses yielded similar results. CONCLUSIONS: Long-term exposure to ambient [Formula: see text] was associated with an increased risk of CKD development. Our findings reinforce the urgency to develop global strategies of air pollution reduction to prevent CKD. https://doi.org/10.1289/EHP3304.

Balancing geo-privacy and spatial patterns in epidemiological studies.

To balance the protection of geo-privacy and the accuracy of spatial patterns, we developed a geo-spatial tool (GeoMasker) intended to mask the residential locations of patients or cases in a geographic information system (GIS). To elucidate the effects of geo-masking parameters, we applied 2010 dengue epidemic data from Taiwan testing the tool's performance in an empirical situation. The similarity of pre- and post-spatial patterns was measured by D statistics under a 95% confidence interval. In the empirical study, different magnitudes of anonymisation (estimated Kanonymity ≥10 and 100) were achieved and different degrees of agreement on the pre- and post-patterns were evaluated. The application is beneficial for public health workers and researchers when processing data with individuals' spatial information.

Enhancing Raman signals through electromagnetic hot zones induced by magnetic dipole resonance of metal-free nanoparticles.

In this study, we found that the large area of electromagnetic field hot zone induced through magnetic dipole resonance of metal-free structures can greatly enhance Raman scattering signals. The magnetic resonant nanocavities, based on high-refractive-index silicon nanoparticles (SiNPs), were designed to resonate at the wavelength of the excitation laser of the Raman system. The well-dispersed SiNPs that were not closely packed displayed significant magnetic dipole resonance and gave a Raman enhancement per unit volume of 59 347. The hot zones of intense electric field were generated not only within the nonmetallic NPs but also around them, even within the underlying substrate. We observed experimentally that gallium nitride (GaN) and silicon carbide (SiC) surfaces presenting very few SiNPs (coverage: <0.3%) could display significantly enhanced (>50%) Raman signals. In contrast, the Raman signals of the underlying substrates were not enhanced by gold nanoparticles (AuNPs), even though these NPs displayed a localized surface plasmon resonance (LSPR) phenomenon. A comparison of the areas of the electric field hot zones (E 2 > 10) generated by SiNPs undergoing magnetic dipole resonance with the electric field hot spots (E 2 > 10) generated by AuNPs undergoing LSPR revealed that the former was approximately 70 times that of the latter. More noteworthily, the electromagnetic field hot zone generated from the SiNP is able to extend into the surrounding and underlying media. Relative to metallic NPs undergoing LSPR, these nonmetallic NPs displaying magnetic dipole resonance were more effective at enhancing the Raman scattering signals from analytes that were underlying, or even far away from, them. This application of magnetic dipole resonance in metal-free structures appears to have great potential for use in developing next-generation techniques for Raman enhancement.

Minimizing Spatial Variability of Healthcare Spatial Accessibility-The Case of a Dengue Fever Outbreak.

Outbreaks of infectious diseases or multi-casualty incidents have the potential to generate a large number of patients. It is a challenge for the healthcare system when demand for care suddenly surges. Traditionally, valuation of heath care spatial accessibility was based on static supply and demand information. In this study, we proposed an optimal model with the three-step floating catchment area (3SFCA) to account for the supply to minimize variability in spatial accessibility. We used empirical dengue fever outbreak data in Tainan City, Taiwan in 2015 to demonstrate the dynamic change in spatial accessibility based on the epidemic trend. The x and y coordinates of dengue-infected patients with precision loss were provided publicly by the Tainan City government, and were used as our model's demand. The spatial accessibility of heath care during the dengue outbreak from August to October 2015 was analyzed spatially and temporally by producing accessibility maps, and conducting capacity change analysis. This study also utilized the particle swarm optimization (PSO) model to decrease the spatial variation in accessibility and shortage areas of healthcare resources as the epidemic went on. The proposed method in this study can help decision makers reallocate healthcare resources spatially when the ratios of demand and supply surge too quickly and form clusters in some locations.

Online platform for applying space-time scan statistics for prospectively detecting emerging hot spots of dengue fever.

BACKGROUND: Cases of dengue fever have increased in areas of Southeast Asia in recent years. Taiwan hit a record-high 42,856 cases in 2015, with the majority in southern Tainan and Kaohsiung Cities. Leveraging spatial statistics and geo-visualization techniques, we aim to design an online analytical tool for local public health workers to prospectively identify ongoing hot spots of dengue fever weekly at the village level. METHODS: A total of 57,516 confirmed cases of dengue fever in 2014 and 2015 were obtained from the Taiwan Centers for Disease Control (TCDC). Incorporating demographic information as covariates with cumulative cases (365 days) in a discrete Poisson model, we iteratively applied space-time scan statistics by SaTScan software to detect the currently active cluster of dengue fever (reported as relative risk) in each village of Tainan and Kaohsiung every week. A village with a relative risk >1 and p value <0.05 was identified as a dengue-epidemic area. Assuming an ongoing transmission might continuously spread for two consecutive weeks, we estimated the sensitivity and specificity for detecting outbreaks by comparing the scan-based classification (dengue-epidemic vs. dengue-free village) with the true cumulative case numbers from the TCDC's surveillance statistics. RESULTS: Among the 1648 villages in Tainan and Kaohsiung, the overall sensitivity for detecting outbreaks increases as case numbers grow in a total of 92 weekly simulations. The specificity for detecting outbreaks behaves inversely, compared to the sensitivity. On average, the mean sensitivity and specificity of 2-week hot spot detection were 0.615 and 0.891 respectively (p value <0.001) for the covariate adjustment model, as the maximum spatial and temporal windows were specified as 50% of the total population at risk and 28 days. Dengue-epidemic villages were visualized and explored in an interactive map. CONCLUSIONS: We designed an online analytical tool for front-line public health workers to prospectively detect ongoing dengue fever transmission on a weekly basis at the village level by using the routine surveillance data.

Spatial decision on allocating automated external defibrillators (AED) in communities by multi-criterion two-step floating catchment area (MC2SFCA).

BACKGROUND: The occurrence of out-of-hospital cardiac arrest (OHCA) is a critical life-threatening event which frequently warrants early defibrillation with an automated external defibrillator (AED). The optimization of allocating a limited number of AEDs in various types of communities is challenging. We aimed to propose a two-stage modeling framework including spatial accessibility evaluation and priority ranking to identify the highest gaps between demand and supply for allocating AEDs. METHODS: In this study, a total of 6135 OHCA patients were defined as demand, and the existing 476 publicly available AEDs locations and 51 emergency medical service (EMS) stations were defined as supply. To identify the demand for AEDs, Bayesian spatial analysis with the integrated nested Laplace approximation (INLA) method is applied to estimate the composite spatial risks from multiple factors. The population density, proportion of elderly people, and land use classifications are identified as risk factors. Then, the multi-criterion two-step floating catchment area (MC2SFCA) method is used to measure spatial accessibility of AEDs between the spatial risks and the supply of AEDs. Priority ranking is utilized for prioritizing deployment of AEDs among communities because of limited resources. RESULTS: Among 6135 OHCA patients, 56.85 % were older than 65 years old, and 79.04 % were in a residential area. The spatial distribution of OHCA incidents was found to be concentrated in the metropolitan area of Kaohsiung City, Taiwan. According to the posterior mean estimated by INLA, the spatial effects including population density and proportion of elderly people, and land use classifications are positively associated with the OHCA incidence. Utilizing the MC2SFCA for spatial accessibility, we found that supply of AEDs is less than demand in most areas, especially in rural areas. Under limited resources, we identify priority places for deploying AEDs based on transportation time to the nearest hospital and population size of the communities. CONCLUSION: The proposed method will be beneficial for optimizing resource allocation while considering multiple local risks. The optimized deployment of AEDs can broaden EMS coverage and minimize the problems of the disparity in urban areas and the deficiency in rural areas.

Spatial Variation and Resuscitation Process Affecting Survival after Out-of-Hospital Cardiac Arrests (OHCA).

BACKGROUND: Ambulance response times and resuscitation efforts are critical predictors of the survival rate after out-of-hospital cardiac arrests (OHCA). On the other hand, rural-urban differences in the OHCA survival rates are an important public health issue. METHODS: We retrospectively reviewed the January 2011-December 2013 OHCA registry data of Kaohsiung City, Taiwan. With particular focus on geospatial variables, we aimed to unveil risk factors predicting the overall OHCA survival until hospital admission. Spatial analysis, network analysis, and the Kriging method by using geographic information systems were applied to analyze spatial variations and calculate the transport distance. Logistic regression was used to identify the risk factors for OHCA survival. RESULTS: Among the 4,957 patients, the overall OHCA survival to hospital admission was 16.5%. In the multivariate analysis, female sex (adjusted odds ratio:, AOR, 1.24 [1.06-1.45]), events in public areas (AOR: 1.30 [1.05-1.61]), exposure to automated external defibrillator (AED) shock (AOR: 1.70 [1.30-2.23]), use of laryngeal mask airway (LMA) (AOR: 1.35 [1.16-1.58]), non-trauma patients (AOR: 1.41 [1.04-1.90]), ambulance bypassed the closest hospital (AOR: 1.28 [1.07-1.53]), and OHCA within the high population density areas (AOR: 1.89 [1.55-2.32]) were positively associated with improved OHCA survival. By contrast, a prolonged total emergency medical services (EMS) time interval was negatively associated with OHCA survival (AOR: 0.98 [0.96-0.99]). CONCLUSIONS: Resuscitative efforts, such as AED or LMA use, and a short total EMS time interval improved OHCA outcomes in emergency departments. The spatial heterogeneity of emergency medical resources between rural and urban areas might affect survival rate.

Cardiac depression induced by cocaine or cocaethylene is alleviated by lipid emulsion more effectively than by sulfobutylether-ß-cyclodextrin.

OBJECTIVES: Cocaine intoxication leads to over 500,000 emergency department visits annually in the United States and ethanol cointoxication occurs in 34% of those cases. Cardiotoxicity is an ominous complication of cocaine and cocaethylene overdose for which no specific antidote exists. Because infusion of lipid emulsion (Intralipid) can treat lipophilic local anesthetic toxicity and cocaine is an amphipathic local anesthetic, the authors tested whether lipid emulsion could attenuate cocaine cardiotoxicity in vivo. The effects of lipid emulsion were compared with the metabolically inert sulfobutylether-ß-cyclodextrin (SBE-ß-CD; Captisol) in an isolated heart model of cocaine and cocaethylene toxicity to determine if capture alone could exert similar benefit as lipid emulsion, which exhibits multimodal effects. The authors then tested if cocaine and cocaethylene, like bupivacaine, inhibit lipid-based metabolism in isolated cardiac mitochondria. METHODS: For whole animal experiments, Sprague-Dawley rats were anesthetized, instrumented, and pretreated with lipid emulsion followed by a continuous infusion of cocaine to assess time of onset of cocaine toxicity. For ex vivo experiments, rat hearts were placed onto a nonrecirculating Langendorff system perfused with Krebs-Henseleit solution. Heart rate, left ventricle maximum developed pressure (LVdevP), left ventricle diastolic pressure, maximum rate of contraction (+dP/dtmax), maximum rate of relaxation (-dP/dtmax), rate-pressure product (RPP = heart rate × LVdevP), and line pressure were monitored continuously during the experiment. A dose response to cocaine (10, 30, 50, and 100 µmol/L) and cocaethylene (10, 30, and 50 µmol/L) was generated in the absence or presence of either 0.25% lipid emulsion or SBE-ß-CD. Substrate-specific rates of oxygen consumption were measured in interfibrillar cardiac mitochondria in the presence of cocaine, cocaethylene, ecgonine, and benzoylecgonine. RESULTS: Treatment with lipid emulsion delayed onset of hypotension (140 seconds vs. 279 seconds; p = 0.008) and asystole (369 seconds vs. 607 seconds; p = 0.02) in whole animals. Cocaine and cocaethylene induced dose-dependent decreases in RPP, +dP/dtmax, and -dP/dtmaxabs (p < 0.0001) in Langendorff hearts; line pressure was increased by cocaine and cocaethylene infusion, but not altered by treatment. Lipid emulsion attenuated cocaine- and cocaethylene-induced cardiac depression. SBE-ß-CD alone evoked a mild cardiodepressant effect (p < 0.0001) but attenuated further cocaine- and cocaethylene-induced decrements in cardiac contractility at high concentrations of drug (100 µmol/L; p < 0.001). Finally, both cocaine and cocaethylene, but not ecgonine and benzoylecgonine, inhibited lipid-dependent mitochondrial respiration by blocking carnitine exchange (p < 0.05). CONCLUSIONS: A commercially available lipid emulsion was able to delay progression of cocaine cardiac toxicity in vivo. Further, it improved acute cocaine- and cocaethylene-induced cardiac toxicity in rat isolated heart while SBE-ß-CD was effective only at the highest cocaine concentration. Further, both cocaine and cocaethylene inhibited lipid-dependent mitochondrial respiration. Collectively, this suggests that scavenging-independent effects of lipid emulsion may contribute to reversal of acute cocaine and cocaethylene cardiotoxicity, and the beneficial effects may involve mitochondrial lipid processing.

Rapid cardiotonic effects of lipid emulsion infusion*.

OBJECTIVES: Bolus infusion of lipid emulsion can reverse cardiac pharmacotoxicity caused by local anesthetics and other lipophilic drugs. The mechanisms of this effect are not completely elucidated. The authors test the hypothesis that lipid emulsion infusion exerts direct, positive inotropic effects. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Rats anesthetized with isoflurane were given intravenous infusions (9 mL/kg over 1 min) of either 20% soybean oil-based emulsion or saline. MEASUREMENTS AND MAIN RESULTS: Arterial pressure and aortic flow were measured continuously in intact animals. Lipid infusion increased aortic flow and arterial pressure faster and to a greater degree than did the same volume of saline infusion. Isolated rat hearts were studied using an isovolumetric, constant flow, nonrecirculating system. Left ventricular pressure was monitored. The infusion of lipid emulsion in the isolated heart dose-dependently increased rate pressure product, dP/dt, -dP/dt, and myocardial oxygen demand. CONCLUSIONS: Lipid emulsion exerts rapid, positive inotropic and positive lusitropic effects in both intact animal and isolated heart models. We hypothesize that this inotropy and the resulting increase in tissue blood flow contribute to the phenomenon of lipid reversal of cardiac toxicity caused by drug overdose.

Epinephrine induces rapid deterioration in pulmonary oxygen exchange in intact, anesthetized rats: a flow and pulmonary capillary pressure-dependent phenomenon.

BACKGROUND: Previous studies indicate epinephrine adversely affects arterial oxygenation when administered in a rat model of local anesthetic overdose. The authors tested whether epinephrine alone exerts similar effects in the intact animal. METHODS: Anesthetized rats received a single intravenous injection of epinephrine (25, 50, or 100 mcg/kg); matched cohorts were pretreated with phentolamine (100 mcg/kg); n = 5 for each of the six treatment groups. Arterial pressure and blood gases were measured at baseline, 1 and 10 min after epinephrine administration. Pulmonary capillary pressures during epinephrine infusion with normal and increased flows were measured in an isolated lung preparation. RESULTS: Epinephrine injection in the intact animal caused hypoxemia, hypercapnia, and acidosis at all doses. Arterial oxygen tension was reduced within 1 min of injection. Hyperlactatemia occurred by 10 min after 50 and 100 mcg/kg. Rate pressure product was decreased by 10 min after 100 mcg/kg epinephrine. Pretreatment with phentolamine attenuated these effects except at 100 mcg/kg epinephrine. In the isolated lung preparation, epinephrine in combination with increased pulmonary flow increased pulmonary capillary pressure and lung water. CONCLUSIONS: Bolus injection of epinephrine in the intact, anesthetized rat impairs pulmonary oxygen exchange within 1 min of treatment. Effects were blunted by α-adrenergic receptor blockade. Edema occurred in the isolated lung above a threshold pulmonary capillary pressure when epinephrine treatment was coupled with an increase in pulmonary flow. These results potentially argue against using traditional doses of epinephrine for resuscitation, particularly in the anesthetized patient.

(Zn,H)-codoped copper oxide nanoparticles via pulsed laser ablation on Cu-Zn alloy in water.

Nanosized (5 to 10 nm) amorphous and crystalline nanocondensates, i.e., metallic α-phase of Zn-Cu alloy in face-centered cubic structure and (Zn,H)-codoped cuprite (Cu2O) with high-pressure-favored close-packed sublattice, were formed by pulsed laser ablation on bulk Cu65Zn35 in water and characterized by X-ray/electron diffractions and optical spectroscopy. The as-fabricated hybrid nanocondensates are darkish and showed photoluminescence in the whole visible region. Further dwelling of such nanocondensates in water caused progressive formation of a rice-like assembly of (Zn,H)-codoped tenorite (CuO) nanoparticles with (001), (100), and {111} preferred orientations, (111) tilt boundary, yellowish color, and minimum bandgap narrowing down to ca. 2.7 eV for potential photocatalytic applications.

Size, composition and structural changes of TiO2 rutile nanoparticles by pulsed laser ablation in water.

The rutile-type TiO2 powders originally whitish and micrometer in size were successfully reduced in size with accompanied structure, composition and optical property change to become dark bluish by pulsed laser ablation in liquid under 532 nm excitation and 400 mJ per pulse at a specified water depth (5 or 15 mm) for up to 30 min. Transmission electron microscopic observations indicated the newly formed anatase nanoparticles are ca. 5 nm in size with spindle-like shape having well-developed {101} faces and -(001) facets for mutual coalescence into unity. The -(001)-specific coalescence twin of anatase was also observed. There are also amorphous nanoparticles in association with anatase, minor brookite and relic rutile with 2 x (110) superstructure. The resultant colloidal TiO2 nanoparticles are (Ti3+, Ti2+, H+) co-signified according to optical spectroscopic results and have a bimodal minimum band gaps 3.12 and 2.66 eV due to nanocrystals and amorphous phase, respectively, for potential optocatalytic applications in UV-visible range.

Pioglitazone attenuates acute cocaine toxicity in rat isolated heart: potential protection by metabolic modulation.

BACKGROUND: The authors tested whether cocaine depresses mitochondrial acylcarnitine exchange and if a drug that enhances glucose metabolism could protect against cocaine-induced cardiac dysfunction. METHODS: Oxygen consumption with and without cocaine was compared in rat cardiac mitochondria using octanoylcarnitine (lipid) or pyruvate (nonlipid) substrates. Isolated hearts from rats with or without a pioglitazone-supplemented diet were exposed to cocaine. RESULTS: The 0.5 mM cocaine inhibited respiration supported by octanoylcarnitine (82 ± 10.4 and 45.7 ± 4.24 ngatomO min⁻¹ · mg⁻¹ · protein ± SEM, for control and cocaine treatment, respectively; P < 0.02) but not pyruvate-supported respiration (281 ± 12.5 and 267 ± 12.7 ngatomO min⁻¹ · mg⁻¹ · protein ± SEM; P = 0.45). Cocaine altered contractility, lusitropy, coronary resistance, and lactate production in isolated heart. These effects were each blunted in pioglitazone-treated hearts. The pioglitazone diet attenuated the drop in the rate-pressure product (P = 0.002), cocaine-induced diastolic dysfunction (P = 0.04), and myocardial vascular resistance (P = 0.05) compared with that of controls. Lactate production was higher in pretreated hearts (P = 0.008) and in ventricular myocytes cultured with pioglitazone (P = 0.0001). CONCLUSIONS: Cocaine inhibited octanoylcarnitine-supported mitochondrial respiration. A pioglitazone diet significantly attenuated the effects of cocaine on isolated heart. The authors postulate that inhibition of acylcarnitine exchange could contribute to cocaine-induced cardiac dysfunction and that metabolic modulation warrants additional study.