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Early assertive pharmacotherapy intervention study for stimulant associated psychosis—a 24-month prospective randomized controlled trial
No full textBackground: Both cocaine and methamphetamine are the top two commonest misused stimulants worldwide. It is well established that stimulant use can induce psychotic disorder, and a substantial proportion of stimulant associated psychosis will convert to schizophrenia. Thus, early assertive pharmacotherapy is in utmost need. Scanty evidence is available on the suitable choices of antipsychotics that can benefit both stimulant use and its associated psychosis.Aims & Objectives: This study aimed to compare the clinical outcomes from using aripiprazole or paliperidone to treatment-as-usual (TaU) in stimulant users with stimulant associated psychosis on their efficacies in treating the psychosis, stimulant dependence, and changes in mood, cognitive and functional outcomes. It also looked into the conversion rate from stimulant-induced psychotic disorder to schizophrenia after the use of early assertive pharmacotherapy among stimulant users.Method: This study was a 24-month, two phases, three-arm, prospective longitudinal interventional study. Consented stimulant users with psychotic symptoms were randomized to receive either aripiprazole, paliperidone or TaU for 12 months in the single-blinded “Active Intervention” phase, followed by another 12 months open-labelled “Observation Maintenance” phase when the allocated interventions could be continued, stopped or changed to other medications. Primary outcomes including: 24-item Brief Psychiatric Rating Scale (BPRS-24), Clinical Global Impression (CGI), Glasgow Antipsychotic Side-effect Scale (GASS), Severity of Dependence Scale (SDS), severity of DSM-5 defined stimulant use disorder (SUD), Stages of Change Readiness and Treatment Eagerness Scale-Drug (SOCRATES-D), and secondary outcomes including: Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Frontal Assessment Battery (FAB), Montreal Cognitive Assessment (MoCA), and Addiction Severity Index-Lite (ASI-Lite) were assessed.Results: 165 stimulant users with psychotic symptoms were randomized. At the end of the “Active Intervention” phase and the “Observation Maintenance” phase, there were no significant intervention group differences in BPRS-24, GASS, CGI-S, SDS and SUD for cocaine, SOCRATES-D, BAI, BDI-II, FAB and ASI-Lite. There could be a potential transient worsening of psychological dependence to methamphetamine when aripiprazole and paliperidone were prescribed in the first six months when compared to TaU group (p Discussion & Conclusions: Clinicians should aware that early antipsychotic pharmacotherapy can help lowering the conversion rate of stimulant induced psychosis to schizophrenia. Both aripiprazole and paliperidone were well tolerated in stimulant users with associated psychosis. Aripiprazole demonstrated significantly better clinical improvement in stimulant associated psychotic symptoms and was able to improve the severity of methamphetamine use disorder than the other two intervention groups. When paliperidone is prescribed to stimulant users with associated psychosis, their cognitive function should be monitored.</p
Whose Visions for What Learning? Perspectives, Policies and Practices in Private Supplementary Tutoring
Get PDFPrivate supplementary tutoring needs more attention. In recent years it has become a huge global phenomenon. In some countries, especially in senior grades but also even in primary schooling, over 70% of students receive private tutoring alongside public schooling. The tutoring may be provided by companies, by teachers securing extra incomes, and by informal suppliers such as university students. In 2023, the size of the industry was estimated at US288 billion by 2030. In comparison, US$97 billion was the estimated need to bridge the financing gap for the United Nations’ Sustainable Development Goal 4 (SDG4) on education. Families invest in tutoring to keep ahead in the competitive environment. In the process, they supplement the learning from schools, and provide employment and incomes for tutors. However, the tutoring can have a problematic backwash on schooling. It also maintains and exacerbates social inequalities, which undermines UNESCO’s goals of equal opportunities for all. Among the core needs is improved regulation. Much can be learned from comparative analysis about what works in different circumstances.published_or_final_versio
Observation of Chiral Topological Transfer in a Non-Hermitian Photonic Lattice
No full textTopological photonic states have garnered a wide range of research interest in photonics due to their robustness against disorders and imperfections. Here, we present a novel topological chiral transfer effect by combining topological pumping and dynamical mode braiding in non-Hermitian photonic lattices. Unlikeconventional topological pumping, the transfer of topological edge states (TESs) exhibits dual asymmetry in both the input edge and propagation direction selections. Furthermore, the large energy gap between TESs and bulk states allows relaxation of adiabatic constraints, leading to a two-order-of-magnitude reduction in device length compared to previous designs, as demonstrated by experiments. Our findings not only advance the understanding of multidegree-of-freedom non-Hermitian dynamics but also offer an accessible approach for developing high-density integrated photonic devices.</p
Pincer-Type Pt(II)-NHC Antibody-Drug Conjugate for HER-2-Targeted Chemoimmunotherapy
Get PDFPlatinum-based chemotherapy drugs play an indispensable role in clinical cancer treatment, but exhibit considerable side effects due to their non-specific mechanism of killing cancer cells and normal cells. In this regard, the use of antibodies conjugated to anti-cancer platinum complexes will enable better differentiation of cancer cells from normal cells. Here, six pincer-platinum(II) NHC (N-heterocyclic carbene) complexes are reported, one of which has an amino group on the N-alkyl group of the NHC ligand. This platinum(II) complex is used as the payload for platinum(II)-based antibody-drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER-2). Notably, this ADC can specifically bind to the HER-2 antigen, distinguish target cells from non-target cells, and exhibit good anti-tumor activity in vitro and in vivo.published_or_final_versio
Genome-wide association study identified novel loci and gene-environment interaction for refractive error in children
Get PDFTo identify novel genetic loci for children refractive error, we performed a meta-analysis of two genome-wide association studies (GWASs) of spherical equivalent (SE) in 1,237 children from the population-based Hong Kong Children Eye Study (HKCES) and the Low Concentration Atropine for Myopia Progression (LAMP) study. Replication was conducted in 4,093 Chinese children and 1,814 Chinese adults. Four lead-SNPs (MIR4275 rs292034, TENM3 rs17074027, LOC101928911 rs6925312 and FAM135B rs4609227) showed genome-wide significant association (P ≤ 5.0 × 10−8) with SE. TENM3 had been associated with myopia in adults before, whilst the other three loci, MIR4275, LOC101928911 and FAM135B, were novel. Significant interaction between genetic risk scores (GRS) and near work on SE was also detected (βinteraction = 0.14, Pinteraction = 0.0003). This study identified novel genetic loci for children refractive error and suggested myopia intervention can be individualized based on the genetic risk of children.published_or_final_versio
The regulatory role of placental extracellular vesicle on trophoblast and endothelial cell functions
No full textExtracellular vesicles (EVs) are cell-derived, membrane-bound vesicles that carry molecular cargo to facilitate communication between cells. During pregnancy, EVs are secreted by the syncytiotrophoblast layer of the placenta villi, where they mediate the functions of resident leukocytes and invading extravillous trophoblasts (EVTs) in the decidua. This study aims to isolate placental EVs (pEVs) from placental explant to examine their regulatory roles on EVT and endothelial cell functions. pEVs were successfully isolated from ex vivo cultured placental explant, which were capable to be internalized by EVTs and endothelial cells. pEVs stimulated the differentiation of trophoblast stem cells (TSCs) and enhanced the migration and invasion abilities of EVTs via CD147 receptor. Conversely, pEVs inhibited the tube formation ability and interleukin-6 (IL-6) secretion of endothelial cells. Together, these findings partially elucidate the role of pEVs during early pregnancy establishment, which may provide insights into pregnancy-related disorders.</p
Global consequences of dam-induced river fragmentation on diadromous migrants: a systematic review and meta-analysis
No full textThe global proliferation of dams has altered flow and sediment regimes in rivers, presenting a major threat to freshwater biodiversity. Diadromous species, such as fishes, decapod crustaceans and gastropods, are particularly susceptible to fragmentation because dams obstruct their breeding migrations between coastal waters and rivers. Although dams have contributed to significant declines in abundance of some commercially important diadromous fishes (salmonids and anguillids) and Macrobrachium shrimps, understanding of the impacts of fragmentation on the majority of diadromous animals is limited. Moreover, the number of species known to have diadromous life cycles has risen substantially during the last four decades, from ~250 to more than 800. This synthesis aims to consolidate the global impacts of fragmentation on diadromous animals and highlight potential knowledge gaps. We identified 338 publications documenting the impacts of dams on diadromous fishes and decapods, but this was reduced to 65 publications after application of our strict selection criteria. Specifically, we only included studies that compared unfragmented (e.g. undammed) or restored (e.g. dams with fish passes) with fragmented (e.g. site above dams) rivers. To assess statistical significance, the results of studies that were replicated sufficiently to enable calculation of standardised effect sizes were also subject to meta-analysis focusing on three topics: impacts of dam-induced fragmentation; efficacy of fish passes; and the mitigative potential of dam removal. Study outcomes were evaluated from five key variables: abundance; species richness; assemblage composition; population genetic diversity; and population genetic structure. We found that fragmentation led to net negative effects across all key variables for diadromous fishes. Fishes with limited jumping or climbing ability and obligate diadromous migrants that cannot persist as landlocked populations were more threatened by fragmentation. However, fishes that were capable climbers or jumpers and facultatively diadromous were nonetheless susceptible to impacts, particularly in their abundance and gene flow between fragmented populations. Installation of fish passes did not lead to positive outcomes, whereas dam removal was effective in restoring connectivity for fishes, suggesting that it is a more effective, albeit potentially contentious, approach (e.g. the dam may serve an important societal need), for restoring habitat connectivity. A smaller number of publications investigated diadromous decapods (seven versus 61 on fishes), and our synthesis of their findings suggests that decapods were vulnerable to habitat alteration by dams, but were less sensitive to their barrier effects because they were better climbers than fishes. Gastropods were the least studied diadromous taxon, and none met our criteria for systematic review or meta-analysis. The imbalance in information about diadromous taxa was compounded by a scarcity of studies from the tropics, particularly in South America, Africa, South Asia, Southeast Asia, and East Asia. These regions support diverse aquatic assemblages so the impacts of dams may be underestimated given existing knowledge gaps. The conservation of diadromous migrants would be best served by avoiding the construction of dams while improving mitigation strategies, such as fish passage design, to limit the most damaging effects of river fragmentation
A probabilistic framework with recurrent mixture density network for reliability analysis of bridge expansion joint under thermal loading
No full textExpansion joints (EJs) are critical components of a bridge to accommodate the temperature-induced movements and prevent structural damage. Predicting the EJ displacements and providing early warnings are crucial to the maintenance and safety of bridges. This paper presents a novel probabilistic framework to predict the EJ displacements, integrating a recurrent mixture density network and Bayesian linear regression. This approach addresses the inherent uncertainties of the measured structural temperatures and linear regression parameters through robust simulations. The Monte Carlo simulation can effectively evaluate the marginal posterior distribution of the EJ displacements. This framework not only derives the critical parameters from the simulations, but also provides the probability distributions associated with the random forecasting errors under significant temperature variations. The recurrent mixture density network, Bayesian linear regression and the combined models, upon examination with different evaluation indicators, prove that the models work well in predicting the probability distributions. The reliability and anomaly indices obtained show that this innovative methodology can provide precise and probabilistic estimation of the factors governing the EJ displacements for steering the early warning systems
Simulation of fire-induced spalling and damage behaviors in granite rock caverns in Hong Kong using thermo-mechanical coupling phase field method
No full textSince the 1980s, the Hong Kong Government has been exploring the construction of rock caverns as a sustainable solution to alleviate land scarcity. Fire safety remains a paramount concern in the operation of underground rock caverns. Fires not only pose significant risks to personnel evacuation and firefighting intervention but also present substantial challenges for post-disaster repair and fire-resistant design for these caverns. Granite formations, which are very common in Hong Kong, are favorable for housing caverns. However, both the granite and its supporting concrete lining in cavern may experience significant mechanical degradation when subjected to high temperatures. To investigate the thermo-mechanical coupling response of rock caverns under fire scenarios, we employed the phase field method (PFM) to simulate a project in Hong Kong. This work explores the heated spalling fracturing and damage behaviors of the lining and surrounding rock under various conditions involving fire scenarios, cavern burial depths, rock stiffness, and presence of rock bolts. The results indicate that the failure of the lining and rock is affected by the fire scenario on the fire-exposed surface, while the burial depth and rock stiffness have minimal impact. Rock bolts can effectively reduce the deformation of intact rock formations which are not subjected the high temperature penetration.</p
Secure Synchronization of Lur’e Systems Under DoS Attacks With Application to Chua’s Circuit: Aperiodic Sampled-Data Control
No full textThis article explores a novel secure synchronization scheme for drive-response Lur’e systems under denial-of-service (DoS) attacks. The main innovative features are characterized by an aperiodic transmission mechanism without attack detection, a resilient sampled-data control linked with timer, and a highly aperiodic-interval-dependent Lyapunov functional. The output error of the drive-response system is aperiodically sampled and transmitted through networks subject to DoS attacks. By applying a timer, this aperiodic transmission mechanism assesses whether the aperiodic sampled-data characteristic is impacted by attacks at any time, thus avoiding the need for attack detection and enhancing its practicality. Correspondingly, a resilient sampled-data control linked with timer is developed, wherein the control signal dynamically changes when not impacted by attacks, improving secure control performance for achieving synchronization. Additionally, a new secure synchronization standard compatible with this scheme is introduced. Based on the framework, secure synchronization analysis and control results are derived through the proposed highly aperiodic-interval-dependent Lyapunov functional. More specially, the matrix variables in this functional are explicitly related to each aperiodic sampling transmission interval, as well as those used for handling nonlinear functions, which contributes to reduced conservativeness in the results. The theoretical advantages of these new methods and results are compared with existing literature. Finally, the novel secure synchronization scheme is applied to two examples to validate the effectiveness and superiority, including a 3-neuron neural network and a chaotic Chua’s circuit.</p