•Examines the impacts of electric LDVs and electric buses on traffic noise and chemical air pollution in Hong Kong.•Reduction in traffic noise can reach 4.4 dbA with all bus fleet electrified.•80% of ...population can benefit from traffic noise reduction from bus electrification.•Greater noise savings can be found in road sections with congestion, dense intersections and a high share of buses in the traffic mix.•Local authorities can prioritize bus routes to be electrified to maximize health co-benefits.
Traffic noise is a growing threat to the urban population. Prolonged exposure to traffic noise has been linked to negative health consequences such as annoyance, sleep disturbances and cardiovascular diseases. While electric vehicles are known to have lower noise profiles, the impacts of electric mobility on traffic noise, especially for electrified heavy-duty vehicles, have not been thoroughly examined. This study aims to examine the impacts of both electric light-duty vehicles and electric buses on traffic noise levels in a highly urbanized city. Traffic noise along the source line and pedestrian network was first estimated and mapped to illustrate its spatiotemporal variations. Then, scenario analysis was used to compare the impacts. Population potentially benefiting from reduced traffic noise in the neighbourhoods and the associated health impacts were also estimated. Results indicate that electric buses have a greater potential to reduce traffic noise, with a maximum reduction of 4.4 dBA during daytime in the urban cores. With all bus fleet electrified, around 60% of the population can benefit from a reduction of 1 dBA at the street environment, 15.3% for 1–2 dBA, and 4.3% for more than 2 dBA. The estimated reduction of preventable deaths and preventable cases of diseases per 100,000 population are 4.15 and 112.99 respectively. The findings shed important insights into prioritizing bus routes to be electrified in urban areas for maximizing health co-benefits.
High‐dose methotrexate (>0.5 g/m2) is among the first‐line chemotherapeutic agents used in treating acute lymphoblastic leukemia (ALL) and osteosarcoma in children. Despite rapid hydration, ...leucovorin rescue, and routine therapeutic drug monitoring, severe toxicity is not uncommon. This study aimed at developing population pharmacokinetic (popPK) models of high‐dose methotrexate for ALL and osteosarcoma and demonstrating the possibility and convenience of popPK model–based individual dose optimization using R and shiny, which is more accessible, efficient, and clinician‐friendly than NONMEM. The final data set consists of 36 ALL (354 observations) and 16 osteosarcoma (585 observations) patients. Covariate model building and parameter estimations were done using NONMEM and Perl‐speaks‐NONMEM. Diagnostic Plots and bootstrapping validated the models’ performance and stability. The dose optimizer developed based on the validated models can obtain identical individual parameter estimates as NONMEM. Compared to calling a NONMEM execution and reading its output, estimating individual parameters within R reduces the execution time from 8.7‐12.8 seconds to 0.4‐1.0 second. For each subject, the dose optimizer can recommend (1) an individualized optimal dose and (2) an individualized range of doses. For osteosarcoma, recommended optimal doses by the optimizer resemble the final doses at which the subjects were eventually stabilized. The dose optimizers developed demonstrated the potential to inform dose adjustments using a model‐based, convenient, and efficient tool for high‐dose methotrexate. Although the dose optimizer is not meant to replace clinical judgment, it provides the clinician with the individual pharmacokinetics perspective by recommending the (range of) optimal dose.
COVID-19 reaffirms the vital role of superspreaders in a pandemic. We propose to broaden the research on superspreaders through integrating human mobility data and geographical factors to identify ...superspreading environment. Six types of popular public facilities were selected: bars, shopping centres, karaoke/cinemas, mega shopping malls, public libraries, and sports centres. A historical dataset on mobility was used to calculate the generalized activity space and space-time prism of individuals during a pre-pandemic period. Analysis of geographic interconnections of public facilities yielded locations by different classes of potential spatial risk. These risk surfaces were weighed and integrated into a "risk map of superspreading environment" (SE-risk map) at the city level. Overall, the proposed method can estimate empirical hot spots of superspreading environment with statistical accuracy. The SE-risk map of Hong Kong can pre-identify areas that overlap with the actual disease clusters of bar-related transmission. Our study presents first-of-its-kind research that combines data on facility location and human mobility to identify superspreading environment. The resultant SE-risk map steers the investigation away from pure human focus to include geographic environment, thereby enabling more differentiated non-pharmaceutical interventions and exit strategies to target some places more than others when complete city lockdown is not practicable.
The hepatitis B X protein (HBx) plays a role in the epigenetic regulation of hepatitis B virus (HBV) replication. This study investigated the effects of HBx mutations on HBV transcription and the ...recruitment of HBx, histone acetyl-transferase P300 and histone deacetylase 1 (HDAC1) to circularized HBV DNA (which resembles covalently closed circular DNA cccDNA). Compared with wild type, majority of mutants had lower levels of intracellular HBV RNA (44-77% reduction) and secretory HBsAg (25-81% reduction), and 12 mutants had a reduction in intracellular encapsidated HBV DNA (33-64% reduction). Eight mutants with >70% reduction in HBV RNA and/or HBsAg were selected for chromatin immunoprecipitation analysis. Four HBx mutants with mutations in amino acid residues 55-60 and 121-126 had a lower degree of HBx-cccDNA association than wild type HBx (mean % input: 0.02-0.64% vs. 3.08% in wild type). A reduced association between cccDNA and P300 (mean % input: 0.69-1.81% vs. 3.48% in wild type) and an augmented association with HDAC1 (mean % input: 4.01-14.0% vs. 1.53% in wild type) were detected. HBx amino acid residues 55-60 and 121-126 may play an important role in HBV transcription regulation, via their impeded interaction with cccDNA and altered recruitment of histone modifying enzymes to cccDNA.
We evaluated the feasibility of existing risk assessment tools for chronic myeloid leukemia (CML) in children. Fifty-five patients with newly diagnosed CML between 1996 and 2019 were included. ...Forty-nine patients presented in chronic phase, thirty-six of whom were treated with upfront tyrosine kinase inhibitor (CP-TKI group); one presented in accelerated phase and four in blastic phase. Treatment, survival, responses, and tolerance were evaluated. All patients in the CP-TKI group received imatinib as their first TKI treatment. The 10-year overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) of TKI-treated group was 97%, 91.4%, and 72.3%, respectively. At 60 months, the rates of major molecular response were 81.2% and deep molecular response was 67.5%. The EUTOS long-term survival (ELTS) risk grouping did not predict OS, PFS, or EFS. The IMAFAIL risk groups were correlated with the risk of imatinib failure. Further studies are required to modify the existing risk assessment tools for children.
FLNC‐related myofibrillar myopathy could manifest as autosomal dominant late‐onset slowly progressive proximal muscle weakness; involvements of cardiac and/or respiratory functions are common. We ...describe 34 patients in nine families of FLNC‐related myofibrillar myopathy in Hong Kong ethnic Chinese diagnosed over the last 12 years, in whom the same pathogenic variant c.8129G>A (p.Trp2710*) was detected. Twenty‐six patients were symptomatic when diagnosed; four patients died of pneumonia and/or respiratory failure. Abnormal amorphous material or granulofilamentous masses were detected in half of the cases, with mitochondrial abnormalities noted in two‐thirds. We also show by haplotype analysis the founder effect associated with this Hong Kong variant, which might have occurred 42 to 71 generations ago or around Tang and Song dynasties, and underlain a higher incidence of myofibrillar myopathy among Hong Kong Chinese. The late‐onset nature and slowly progressive course of the highly penetrant condition could have significant impact on the family members, and an early diagnosis could benefit the whole family. Considering another neighboring founder variant in FLNC in German patients, we advocate development of specific therapies such as chaperone‐based or antisense oligonucleotide strategies for this particular type of myopathy.
FLNC‐related myofibrillar myopathycould manifest as autosomal dominant late‐onset slowly progressive proximal muscle weakness; involvements of cardiac and/or respiratory functions are common. We describe 34 patients in nine families of FLNC‐related myofibrillar myopathy in Hong Kong ethnic Chinese diagnosed over the last 12 years, in whom the same pathogenic variant c.8129G>A (p.Trp2710*) was detected. Abnormal amorphous material or granulofilamentous masses were detected in half of the cases, with mitochondrial abnormalities noted in two thirds. We also demonstrate by haplotype analysis the founder effect associated with this Hong Kong variant.
It is now well established that the developing embryo is very sensitive to oxidative stress, which is a contributing factor to pregnancy-related disorders. However, little is known about the effects ...of reactive oxygen species (ROS) on the embryonic cardiovascular system due to a lack of appropriate ROS control method in the placenta. In this study, a small molecule called 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH), a free radicals generator, was used to study the effects of oxidative stress on the cardiovascular system during chick embryo development. When nine-day-old (stage HH 35) chick embryos were treated with different concentrations of AAPH inside the air chamber, it was established that the LD50 value for AAPH was 10 µmol/egg. At this concentration, AAPH was found to significantly reduce the density of blood vessel plexus that was developed in the chorioallantoic membrane (CAM) of HH 35 chick embryos. Impacts of AAPH on younger embryos were also examined and discovered that it inhibited the development of vascular plexus on yolk sac in HH 18 embryos. AAPH also dramatically repressed the development of blood islands in HH 3+ embryos. These results implied that AAPH-induced oxidative stress could impair the whole developmental processes associated with vasculogenesis and angiogenesis. Furthermore, we observed heart enlargement in the HH 40 embryo following AAPH treatment, where the left ventricle and interventricular septum were found to be thickened in a dose-dependent manner due to myocardiac cell hypertrophy. In conclusion, oxidative stress, induced by AAPH, could lead to damage of the cardiovascular system in the developing chick embryo. The current study also provided a new developmental model, as an alternative for animal and cell models, for testing small molecules and drugs that have anti-oxidative activities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The hepatitis B core protein (HBc) has been suggested to interact with covalently closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription. However, direct evidence is lacking. ...We aimed to identify the specific HBc region(s) responsible for transcription regulation and its interaction with cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were measured. The association of cccDNA with mutant HBc and histone acetyltransferases (HATs) was assessed by chromatin immunoprecipitation (ChIP). Compared with wild-type HBc, HBc mutants with mutations in clusters III and IV resulted in a significant reduction in HBV RNA levels (all P < 0.05). HBc arginine clusters III and IV mutants also had a significantly lower levels of intracellular HBV DNA (<5% of wild-type; P < 0.001) and HBsAg (<10% of wild-type; P < 0.0001). cccDNA-ChIP assay demonstrated that HBc clusters III and IV mutants had a smaller degree of association with cccDNA (P < 0.001). In the HBc mutants, the association between HATs with cccDNA were reduced. In conclusion, HBc-CTD arginine residues at clusters III and IV play an important role in the regulation of HBV transcription as well as subsequent replication steps, likely through the reduced interaction of HBc with cccDNA and reduced acetylation of cccDNA-bound histones. These findings may provide clues to the identification of novel therapeutic targets against HBV.
•We assessed the role of hepatitis B core protein (HBc) in HBV transcription by mutational analysis.•HBV transcription levels in HBc mutants with mutations at arginine clusters III and IV were lower than wild-type HBc.•The interaction between HBc clusters III and IV mutants and covalently closed circular (ccc) DNA were reduced.•In strains with HBc clusters III and IV mutations, the recruitment of histone acetyltransferases to cccDNA is impeded.•HBc arginine clusters III and IV are potential therapeutic target sites against HBV replication.
The sustainable transport pathway Loo, Becky P. Y.; Tsoi, Ka Ho
Journal of transport and land use,
01/2018, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In this paper, a holistic strategy of the "Five Transformations" is introduced to offer a comprehensive and synergetic theory to tackle various daunting challenges faced by the transport sector and ...ultimately pave the way to sustainable transport. The Five Transformations span across city development, the economy, vehicle technology, modal-split and lifestyles at various geographical scales. Building on the current literature and empirical evidence, this paper advocates for fundamental changes in all aspects of the society beyond transportation. To move forward, this paper scrutinizes the association between land-use planning and the Five Transformations. It is clear that land-use policies are important drivers in implementing and reinforcing the policy instruments under the Five Transformations.
Estimated time of arrival (ETA) is essential to enable various intelligent transportation services and reduce passenger waiting time. Estimating the time of arrival of public transport in a highly ...dynamic and uncertain transportation system could be challenging. Many indirect factors beyond the remaining travel distance could dramatically deviate the time of arrival from the original schedule. Existing distance-based estimation methods disregarding those factors usually result in inaccurate estimations. In this paper, we propose a new deep learning model, called Deep Encoder Cross Network (DECN), to improve the ETA prediction based on multiple non-distance-based factors such as weather, road speed and congestion, and traffic composition. Unlike most regression tasks that output the target directly, we predict the ETA residual over the location-based ETA prediction. To effectively learn in the large and sparse input feature space, we use a new neural network structure consisting of three main components. First, a deep neural network is responsible for modeling explicit feature interactions. Second, an encoder network is constructed to reduce the input feature dimensionality. Third, a cross-network is introduced to learn from the implicit feature interactions. We conduct extensive experiments on a large real-world bus ETA dataset of Hong Kong, which contains about 2.95 × 10 8 rows with 27 different features on an 84-dimensional space. The results show that the deep learning approach with the DECN model can improve the ETA error by 11% on average, and 49% for late arrival. The proposed approach can be further improved and extended to estimate other traffic information by incorporating non-distance-based related information.
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