Selection and behavioral responses of health insurance subsidies in the long run: Evidence from a field experiment in Ghana.

We study the effects of a health insurance subsidy in Ghana, where mandates are not enforceable. We randomly provide different levels of subsidy (1/3, 2/3, and full) and evaluate the impact at 7 months and 3 years after the intervention. We find that a one-time subsidy increased insurance enrollment for all groups in both the short and long runs, but health care utilization in the long run increased only for the partial subsidy group. We find supportive evidence that ex-post behavioral responses rather than ex-ante selective enrollment explain the long-run health care utilization results.

Risk compensation after COVID-19 vaccination: Evidence from vaccine rollout by exact birth date in South Korea.

We utilize the phased rollout of COVID-19 vaccines by exact birth date in South Korea as a natural experiment for testing risk compensation. People may resume face-to-face social activities following vaccination because they perceive lower risk of infection. Applying a regression discontinuity design based on birth date cutoffs for vaccine eligibility, we find no evidence of risk-compensating behaviors, as measured by large, high-frequency data from credit card and airline companies as well as survey data. We find some evidence of self-selection into vaccine take-up based on perception toward vaccine effectiveness and side effects, but the treatment effects do not differ between compliers and never-takers.

Development of a Polymersome-Based Nanomedicine for Chemotherapeutic and Sonodynamic Combination Therapy.

In anticancer therapy, combination therapy has been suggested as an alternative to the insufficient therapeutic efficacy of single therapy. Among combination therapies, combination chemo- and photodynamic therapy are actively investigated. However, photodynamic therapy shows a limitation in the penetration depth of the laser. Therefore, sonodynamic therapy (SDT), using ultrasound instead of a laser as a trigger, is an upcoming strategy for deep tumors. Additionally, free drugs are easily degraded by enzymes, have difficulty in reaching the target site, and show side effects after systemic administration; therefore, the development of drug delivery systems is desirable for sufficient drug efficacy for combination therapy. However, nanocarriers, such as microbubbles, and albumin nanoparticles, are unstable in the body and show low drug-loading efficiency. Here, we propose polylactide (PLA)-poly (ethylene glycol) (PEG) polymersomes (PLs) with a high drug loading rate of doxorubicin (DOX) and verteporfin (VP) for effective combination therapy in both in vitro and in vivo experiments. The cellular uptake efficiency and cytotoxicity test results of VP-DOX-PLs were higher than that of single therapy. Moreover, in vivo biodistribution showed the accumulation of the VP-DOX-PLs in tumor regions. Therefore, VP-DOX-PLs showed more effective anticancer efficacy than either single therapy in vivo. These results suggest that the combination therapy of SDT and chemotherapy could show novel anticancer effects using VP-DOX-PLs.

Development of Polymersomes Co-Delivering Doxorubicin and Melittin to Overcome Multidrug Resistance.

Multidrug resistance (MDR) is one of the major barriers in chemotherapy. It is often related to the overexpression of efflux receptors such as P-glycoprotein (P-gp). Overexpressed efflux receptors inhibit chemotherapeutic efficacy by pumping out intracellularly delivered anticancer drugs. In P-gp-mediated MDR-related pathways, PI3K/Akt and NF-kB pathways are commonly activated signaling pathways, but these pathways are downregulated by melittin, a main component of bee venom. In this study, a polymersome based on a poly (lactic acid) (PLA)-hyaluronic acid (HA) (20k-10k) di-block copolymer and encapsulating melittin and doxorubicin was developed to overcome anticancer resistance and enhance chemotherapeutic efficacy. Through the simultaneous delivery of doxorubicin and melittin, PI3K/Akt and NF-κB pathways could be effectively inhibited, thereby downregulating P-gp and successfully enhancing chemotherapeutic efficacy. In conclusion, a polymersome carrying an anticancer drug and melittin could overcome MDR by regulating P-gp overexpression pathways.

Ultra-Sensitive Determination of Particulate, Gaseous Inorganic and Organic Iodine-129 and Iodine-127 in Ambient Air.

Atmospheric iodine cycling is of significance in climate change and environmental and health impacts. To better explore speciation transformation of atmospheric stable and radioactive iodine, an ultra-sensitive analytical method was established for determination of 129I and 127I in particulate, gaseous inorganic, and gaseous organic species, which was conducted with a self-designed cascade sampling apparatus, followed by their separation with a pyrolysis system and accelerator mass spectrometry and ICP-MS measurements. Combustion protocols for three sampling matrices and NaOH concentration for iodine trapping were optimized to achieve a safe analytical procedure with a high chemical yield of iodine. Based on the lowest concentrations of 129I and 127I, a suitable activated carbon product for adsorption of gaseous organic iodine was carefully selected. The detection limits of the three species were 0.30-2.21 ng m-3 for 127I and 0.05-0.22 × 105 atoms m-3 for 129I. This newly established method was successfully applied to analyze the levels and species of 129I and 127I in ambinet air from Xi'an, China, from May to August, 2020. Gaseous organic iodine was found to be the dominant species of 127I and 129I, accounting for about half of total iodine, and gaseous inorganic iodine and particulate iodine accounted for one-quarter each during the whole sampling period. Speciation variation of 129I and 127I indicates that speciation transformation apparently occurred at the turn of spring and summer, mainly between particulate and gaseous organic iodine. This study has implications on delicate tracing of the atmospheric behavior of iodine with long-lived anthropogenic 129I.

Changes in the ozone chemical regime over the contiguous United States inferred by the inversion of NOx and VOC emissions using satellite observation.

To investigate changes in the ozone (O3) chemical production regime over the contiguous United States (CONUS) with accurate knowledge of concentrations of its precursors, we applied an inverse modeling technique with Ozone Monitoring Instrument (OMI) tropospheric nitrogen dioxide (NO2) and total formaldehyde (HCHO) retrieval products in the summers of 2011, 2014, and 2017, years in which United States National Emission Inventory were based. The inclusion of dynamic chemical lateral boundary conditions and lightning-induced nitric oxide emissions significantly account for the contribution of background sources in the free troposphere. Satellite-constrained nitrogen oxide (NOx) and non-methane volatile organic compounds (NMVOCs) emissions mitigate the discrepancy between satellite and modeled columns: the inversion suggested 2.33-2.84 (1.07-1.34) times higher NOx over the CONUS (over urban regions) and 0.28-0.81 times fewer NMVOCs emissions over the southeastern United States. The model-derived HCHO/NO2 column ratio shows gradual spatial changes in the O3 production regime near urban cores relative to previously defined threshold values representing NOx and VOC sensitive conditions. We also found apparent shifts from the NOx-saturated regime to the transition regime (or the transition regime to the NOx-limited regime) over the major cities in the western United States. In contrast, rural areas, especially in the east-southeastern United States, exhibit a decreased HCHO/NO2 column ratio by -1.30 ± 1.71 with a reduction in HCHO column primarily driven by meteorology, becoming sensitive to VOC emissions. Results show that incorporating satellite observations into numerical modeling could help policymakers implement appropriate emission control policies for O3 pollution.

Simultaneous removal of radioactive cesium and strontium from seawater using a highly efficient Prussian blue-embedded alginate aerogel.

Radioactive cesium (137Cs) and strontium (90Sr) contaminants in seawater have been a serious problem since the Fukushima accident in 2011 due to their long-term health risks. For the effective and simultaneous removal of radioactive cesium (137Cs) and strontium (90Sr) from seawater, a Prussian blue (PB)-immobilized alginate aerogel (PB-alginate aerogel) was fabricated and its adsorption performance was evaluated. PB nanoparticles were homogeneously dispersed in the three-dimensional porous alginate aerogel matrix, which enabled facile contact with seawater. The PB-alginate aerogel exhibited Cs+ and Sr2+ adsorption capacities of 19.88 and 20.10 mg/g, respectively, without substantial interference because Cs+ and Sr2+ adsorption occurred at different adsorption sites on the composite. The Cs+ and Sr2+ adsorption onto the PB-alginate aerogel was completed within 3 h due to the highly porous morphology of the aerogel. The Cs+ and Sr2+ adsorption behaviors on the PB-alginate aerogel were systematically investigated under various conditions. Compared with Cs+ adsorption, Sr2+ adsorption onto the PB-alginate aerogel was more strongly influenced by competing cations (Na+, Mg2+, Ca2+, and K+) in seawater. 137Cs and 90Sr removal tests in real seawater demonstrated the practical feasibility of the PB-alginate aerogel as an adsorbent.

Development of an ultrasound triggered nanomedicine-microbubble complex for chemo-photodynamic-gene therapy.

Recently, combination therapy has received much attention because of its highly therapeutic effect in various types of cancers. In particular, chemo-photodynamic combination therapy has been considered as an outstanding strategy. However, an abnormal increase in tumor angiogenesis caused by reactive oxygen species (ROS) generated during photodynamic therapy (PDT) has been reported. In this study, the complex of doxorubicin (DOX)-encapsulating anti-angiogenic small interfering RNA (siRNA) nanoparticle and chlorin e6 (Ce6)-encapsulating microbubble has been developed to suppress tumor angiogenesis. The first compartment, doxorubicin-encapsulating siRNA nanoparticle, was electrostatically coated using two biocompatible polymers to prevent the damage of genetic materials. The other part, Ce6-encapsulating microbubble, serves as an ultrasound-triggered local delivery system as well as a drug carrier. Both the in vitro and in vivo experimental results demonstrate successful inhibition of angiogenesis with a minimized damage of siRNAs caused by ROS as well as improved therapeutic effect by chemo-photodynamic-gene triple combination therapy using ultrasound-triggered local delivery.

Mosaicking Opportunistically Acquired Very High-Resolution Helicopter-Borne Images over Drifting Sea Ice Using COTS Sensors.

Observing sea ice by very high-resolution (VHR) images not only improves the quality of lower-resolution remote sensing products (e.g., sea ice concentration, distribution of melt ponds and pressure ridges, sea ice surface roughness, etc.) by providing details on the ground truth of sea ice, but also assists sea ice fieldwork. In this study, two fieldwork-based methods are proposed, one for the practical acquisition of VHR images over drifting Arctic sea ice using low-cost commercial off-the-shelf (COTS) sensors equipped on a helicopter, and the other for quantifying the compensating effect from continuously drifting sea ice that reduces geolocation uncertainty in the image mosaicking procedure. The drifting trajectory of the target ice was yielded from that recorded by an icebreaker that was tightly anchored to the floe and was then used to reversely compensate the locations of acquired VHR images. After applying the compensation, three-dimensional geolocation errors of the VHR images were decreased by 79.3% and 24.2% for two pre-defined image groups, respectively. The enhanced accuracy of the imaging locations was affected by imaging duration causing variable drifting distances of individual images. Further applicability of the mosaicked VHR image was discussed by comparing it with a TerraSAR-X synthetic aperture radar image containing the target ice, suggesting that the proposed methods can be used for precise comparison with satellite remote sensing products.

Weavable and Highly Efficient Organic Light-Emitting Fibers for Wearable Electronics: A Scalable, Low-Temperature Process.

Fiber-based wearable displays, one of the most desirable requisites of electronic textiles (e-textiles), have emerged as a technology for their capability to revolutionize textile and fashion industries in collaboration with the state-of-the-art electronics. Nonetheless, challenges remain for the fibertronic approaches, because fiber-based light-emitting devices suffer from much lower performance than those fabricated on planar substrates. Here, we report weavable and highly efficient fiber-based organic light-emitting diodes (fiber OLEDs) based on a simple, cost-effective and low-temperature solution process. The values obtained for the fiber OLEDs, including efficiency and lifetime, are similar to that of conventional glass-based counterparts, which means that these state-of-the-art, highly efficient solution processed planar OLEDs can be applied to cylindrical shaped fibers without a reduction in performance. The fiber OLEDs withstand tensile strain up to 4.3% at a radius of 3.5 mm and are verified to be weavable into textiles and knitted clothes by hand-weaving demonstrations. Furthermore, to ensure the scalability of the proposed scheme fiber OLEDs with several diameters of 300, 220, 120, and 90 µm, thinner than a human hair, are demonstrated successfully. We believe that this approach, suitable for cost-effective reel-to-reel production, can realize low-cost commercially feasible fiber-based wearable displays in the future.

Islandinium minutum subsp. barbatum subsp. nov. (Dinoflagellata), a New Organic-Walled Dinoflagellate Cyst from the Western Arctic: Morphology, Phylogenetic Position Based on SSU rDNA and LSU rDNA, and Distribution.

A study of modern sediment from the Western Arctic has revealed the presence of a distinctive brown-colored cyst with a spherical central body bearing unbranched processes that are usually solid with a small basal pericoel. Distinctive barbs project from some processes, and process tips are usually minutely expanded into conjoined barbs. The archeopyle is apical and saphopylic. This cyst corresponds to Islandinium? cezare morphotype 2 of Head et al. (2001, J. Quat. Sci., 16:621). Phylogenetic analyses based on the small and large subunit rRNA genes infer close relationship with Islandinium minutum, the type of which is that of the genus. Re-examination of specimens of I. minutum reveals the presence of minute barbs on its processes, but differences with Islandinium? cezare morphotype 2 remain based on size, process distribution, and barb development. Furthermore, the internal transcribed spacer shows I. minutum to be distinct from this morphotype. On the basis of these small but discrete differences, we propose the new subspecies Islandinium minutum subsp. barbatum subsp. nov. Molecular sequencing of other cysts encountered, namely Echinidinium karaense, an unidentified flattened cyst, and "Polykrikos quadratus", places them in the Monovela clade, the latter showing greater morphological variability than previously thought.

Promotion and Persistence of HIV Testing and HIV/AIDS Knowledge: Evidence From a Randomized Controlled Trial in Ethiopia.

We use data from a randomized controlled trial in Ethiopia and examine the causal effects of HIV/AIDS education, home-based voluntary HIV counseling and testing (VCT), and conditional cash transfers (CCT) for facility-based VCT on HIV/AIDS knowledge and demand for HIV testing. HIV/AIDS education significantly increases HIV/AIDS knowledge but has a limited effect on testing take-up. However, when HIV/AIDS education is combined with either home-based VCT or CCT for facility-based VCT, take-up increases substantially by about 63 and 57 percentage points, respectively. We also demonstrate evidence of persistence in test-taking behavior, where past HIV testing does not dampen demand for testing. Lastly, we find suggestive evidence that home-based VCT could be more effective at detecting HIV-positive cases relative to CCT for facility-based VCT. Our findings highlight the importance of geographic accessibility in the testing decision and persistence in demand for HIV testing. Copyright © 2016 John Wiley & Sons, Ltd.

Anti-VEGF PolysiRNA Polyplex for the Treatment of Choroidal Neovascularization.

Choroidal neovascularization (CNV) is a major cause of severe vision loss in patients with age-related macular degeneration (AMD). Present ocular siRNA delivery technology is limited due to poor delivery through the retina to the choroid, where CNV originates. Our goal was to develop an optimized nanosized polyRNAi-based therapeutic delivery system to the subretinal space. We developed it by siRNA multimerization (polysiRNA) followed by coating with branched polyethylenimine and hyaluronic acid, and then evaluated its efficacy in vitro and in vivo. The polysiRNA polyplex showed a narrow size distribution (260.7 ± 43.27 nm) and negative charge (-4.98 ± 0.47 mV) owing to the hyaluronic acid outer layer. In vitro uptake of the polysiRNA polyplex by human ARPE cells was discovered, and the direct inhibition of VEGF mRNA translation was confirmed in B16F10 cells. The intravitreally administered polysiRNA polyplex overcame both the vitreous and retina barriers in vivo and reached the subretinal space efficiently. Intravitreal injection of the polysiRNA polyplex was not toxic to the retina in histopathology. Furthermore, intravitreal injections of the polysiRNA polyplex at both 1 and 7 days after laser photocoagulation inhibited laser-induced choroidal neovascularization, compared to that of the control (p < 0.05). These results suggest that anti-VEGF polysiRNA polyplexes show great potential in delivering multimeric RNAi-based therapeutics to treat retinal or choroidal disorders.

Compensation Method of Natural Head Movement for Gaze Tracking System Using an Ultrasonic Sensor for Distance Measurement.

Most gaze tracking systems are based on the pupil center corneal reflection (PCCR) method using near infrared (NIR) illuminators. One advantage of the PCCR method is the high accuracy it achieves in gaze tracking because it compensates for the pupil center position based on the relative position of corneal specular reflection (SR). However, the PCCR method only works for user head movements within a limited range, and its performance is degraded by the natural movement of the user's head. To overcome this problem, we propose a gaze tracking method using an ultrasonic sensor that is robust to the natural head movement of users. Experimental results demonstrate that with our compensation method the gaze tracking system is more robust to natural head movements compared to other systems without our method and commercial systems.

Extract of Ginkgo Biloba Ameliorates Streptozotocin-Induced Type 1 Diabetes Mellitus and High-Fat Diet-Induced Type 2 Diabetes Mellitus in Mice.

Diabetes mellitus (DM) is caused by either destruction of pancreatic ß-cells (type 1 DM) or unresponsiveness to insulin (type 2 DM). Conventional therapies for diabetes mellitus have been developed but still needs improvement. Many diabetic patients have complemented conventional therapy with alternative methods including oral supplementation of natural products. In this study, we assessed whether Ginkgo biloba extract (EGb) 761 could provide beneficial effects in the streptozotocin-induced type 1 DM and high-fat diet-induced type 2 DM murine model system. For the type 1 DM model, streptozotocin-induced mice were orally administered EGb 761 for 10 days prior to streptozotocin injection and then again administered EGb 761 for an additional 10 days. Streptozotocin-treated mice administered EGb 761 exhibited lower blood triglyceride levels, lower blood glucose levels and higher blood insulin levels compared to streptozotocin-treated mice. Furthermore, liver LPL and liver PPAR-α were increased whereas IL-1ß and TNF-α were decreased in streptozotocin-injected mice treated with EGb 761 compared to mice injected with streptozotocin alone. For the type 2 DM model, mice were given high-fat diet for 60 days and then orally administered EGb 761 every other day for 80 days. We found that mice given a high-fat diet and EGb 761 showed decreased blood triglyceride levels, increased liver LPL, increased liver PPAR-α and decreased body weight compared to mice given high-fat diet alone. These results suggest that EGb 761 can exert protective effects in both type 1 and type 2 DM murine models.

Using optimal interpolation to assimilate surface measurements and satellite AOD for ozone and PM2.5: A case study for July 2011.

UNLABELLED: We employed an optimal interpolation (OI) method to assimilate AIRNow ozone/PM2.5 and MODIS (Moderate Resolution Imaging Spectroradiometer) aerosol optical depth (AOD) data into the Community Multi-scale Air Quality (CMAQ) model to improve the ozone and total aerosol concentration for the CMAQ simulation over the contiguous United States (CONUS). AIRNow data assimilation was applied to the boundary layer, and MODIS AOD data were used to adjust total column aerosol. Four OI cases were designed to examine the effects of uncertainty setting and assimilation time; two of these cases used uncertainties that varied in time and location, or "dynamic uncertainties." More frequent assimilation and higher model uncertainties pushed the modeled results closer to the observation. Our comparison over a 24-hr period showed that ozone and PM2.5 mean biases could be reduced from 2.54 ppbV to 1.06 ppbV and from -7.14 µg/m³ to -0.11 µg/m³, respectively, over CONUS, while their correlations were also improved. Comparison to DISCOVER-AQ 2011 aircraft measurement showed that surface ozone assimilation applied to the CMAQ simulation improves regional low-altitude (below 2 km) ozone simulation. IMPLICATIONS: This paper described an application of using optimal interpolation method to improve the model's ozone and PM2.5 estimation using surface measurement and satellite AOD. It highlights the usage of the operational AIRNow data set, which is available in near real time, and the MODIS AOD. With a similar method, we can also use other satellite products, such as the latest VIIRS products, to improve PM2.5 prediction.

A new gaze estimation method considering external light.

Gaze tracking systems usually utilize near-infrared (NIR) lights and NIR cameras, and the performance of such systems is mainly affected by external light sources that include NIR components. This is ascribed to the production of additional (imposter) corneal specular reflection (SR) caused by the external light, which makes it difficult to discriminate between the correct SR as caused by the NIR illuminator of the gaze tracking system and the imposter SR. To overcome this problem, a new method is proposed for determining the correct SR in the presence of external light based on the relationship between the corneal SR and the pupil movable area with the relative position of the pupil and the corneal SR. The experimental results showed that the proposed method makes the gaze tracking system robust to the existence of external light.

Broken Inversion Symmetry in Van Der Waals Topological Ferromagnetic Metal Iron Germanium Telluride.

Inversion symmetry breaking is critical for many quantum effects and fundamental for spin-orbit torque, which is crucial for next-generation spintronics. Recently, a novel type of gigantic intrinsic spin-orbit torque is established in the topological van der Waals (vdW) magnet iron germanium telluride. However, it remains a puzzle because no clear evidence exists for interlayer inversion symmetry breaking. Here, the definitive evidence of broken inversion symmetry in iron germanium telluride directly measured by the second harmonic generation (SHG) technique is reported. The data show that the crystal symmetry reduces from centrosymmetric P63/mmc to noncentrosymmetric polar P3m1 space group, giving the threefold SHG pattern with dominant out-of-plane polarization. Additionally, the SHG response evolves from an isotropic pattern to a sharp threefold symmetry upon increasing Fe deficiency, mainly due to the transition from random defects to ordered Fe vacancies. Such SHG response is robust against temperature, ensuring unaltered crystalline symmetries above and below the ferromagnetic transition temperature. These findings add crucial new information to the understanding of this interesting vdW metal, iron germanium telluride: band topology, intrinsic spin-orbit torque, and topological vdW polar metal states.

Lipid-coated gold nanorods for photoimmunotherapy of primary breast cancer and the prevention of metastasis.

Nanomedicines hold promise for the treatment of various diseases. However, treating cancer metastasis remains highly challenging. In this study, we synthesized gold nanorods (AuNRs) containing (α-GC), an immune stimulator, for the treatment of primary cancer, metastasis, and recurrence of the cancer. Therefore, the AuNR were coated with lipid bilayers loaded with α-GC (α-LA). Upon irradiation with 808 nm light, α-LA showed a temperature increase. Intra-tumoral injection of α-LA in mice and local irradiation of the 4T1 breast cancer tumor effectively eliminated tumor growth. We found that the presence of α-GC in α-LA activated dendritic cells and T cells in the spleen, which completely blocked the development of lung metastasis. In mice injected with α-LA for primary breast cancer treatment, we observed antigen-specific T cell responses and increased cytotoxicity against 4T1 cells. We conclude that α-LA is promising for the treatment of both primary breast cancer and its metastasis.

Antitumor activity of cell-permeable p18(INK4c) with enhanced membrane and tissue penetration.

Practical methods to deliver proteins systemically in animals have been hampered by poor tissue penetration and inefficient cytoplasmic localization of internalized proteins. We therefore pursued the development of improved macromolecule transduction domains (MTDs) and tested their ability to deliver therapeutically active p18(INK4c). MTD103 was identified from a screen of 1,500 signal peptides; tested for the ability to promote protein uptake by cells and tissues; and analyzed with regard to the mechanism of protein uptake and the delivery of biologically active p18(INK4c) into cancer cells. The therapeutic potential of cell-permeable MTD103p18(INK4c) (CP-p18(INK4c)) was tested in the HCT116 tumor xenograft model. MTD103p18(INK4c) appeared to traverse plasma membranes directly, was transferred from cell-to-cell and was therapeutically effective against cancer xenografts, inhibiting tumor growth by 86-98% after 5 weeks (P < 0.05). The therapeutic responses to CP-p18(INK4c) were accompanied by high levels of apoptosis in tumor cells. In addition to enhancing systemic delivery of CP-p18(INK4c) to normal tissues and cancer xenografts, the MTD103 sequence delayed protein clearance from the blood, liver and spleen. These results demonstrate that macromolecule intracellular transduction technology (MITT), enabled by MTDs, may provide novel protein therapies against cancer and other diseases.