Cracks in concrete can self-heal when exposed to prolonged wetting, but this is limited to narrow cracks. In practice, cracks>0.2mm cause leakage and impair performance of structures. The potential ...of superabsorbent polymers (SAPs) to self-seal such cracks was investigated via transport experiments, microscopy and modelling. Forty samples containing SAP and through-thickness cracks were subjected to 0.12wt.% NaCl at 4m/m pressure gradient to simulate groundwater seepage. Results show that SAP can re-swell and seal cracks, for example in the case of 0.3mm cracks reducing peak flow rate and total flow by 85% and 98% respectively. Increasing SAP dosage accelerates sealing, but imparts a strength penalty and this limits practical applications. Modelling suggests that the effectiveness of SAP can be enhanced by increasing its re-swelling ratio and particle size, and depressing its initial swelling. These variables increase the SAP exposed in a crack and the gel volume available to seal it.
Bacterial biofilms are associated with numerous human infections. The predominant protein expressed in enteric biofilms is the amyloid curli, which forms highly immunogenic complexes with DNA. ...Infection with curli-expressing bacteria or systemic exposure to purified curli-DNA complexes triggers autoimmunity via the generation of type I interferons (IFNs) and anti-double-stranded DNA antibodies. Here, we show that DNA complexed with amyloid curli powerfully stimulates Toll-like receptor 9 (TLR9) through a two-step mechanism. First, the cross beta-sheet structure of curli is bound by cell-surface Toll-like receptor 2 (TLR2), enabling internalization of the complex into endosomes. After internalization, the curli-DNA immune complex binds strongly to endosomal TLR9, inducing production of type I IFNs. Analysis of wild-type and TLR2-deficient macrophages showed that TLR2 is the major receptor that drives the internalization of curli-DNA complexes. Suppression of TLR2 internalization via endocytosis inhibitors led to a significant decrease in Ifnβ expression. Confocal microscopy analysis confirmed that the TLR2-bound curli was required for shuttling of DNA to endosomal TLR9. Structural analysis using small-angle X-ray scattering revealed that incorporation of DNA into curli fibrils resulted in the formation of ordered curli-DNA immune complexes. Curli organizes parallel, double-stranded DNA rods at an inter-DNA spacing that matches up well with the steric size of TLR9. We also found that production of anti-double-stranded DNA autoantibodies in response to curli-DNA was attenuated in TLR2- and TLR9-deficient mice and in mice deficient in both TLR2 and TLR9 compared to wild-type mice, suggesting that both innate immune receptors are critical for shaping the autoimmune adaptive immune response. We also detected significantly lower levels of interferon-stimulated gene expression in response to purified curli-DNA in TLR2 and TLR9 deficient mice compared to wild-type mice, confirming that TLR2 and TLR9 are required for the induction of type I IFNs. Finally, we showed that curli-DNA complexes, but not cellulose, were responsible elicitation of the immune responses to bacterial biofilms. This study defines the series of events that lead to the severe pro-autoimmune effects of amyloid-expressing bacteria and suggest a mechanism by which amyloid curli acts as a carrier to break immune tolerance to DNA, leading to the activation of TLR9, production of type I IFNs, and subsequent production of autoantibodies.
Aim
Hong Kong's existing mental health services are inadequate in addressing young people's needs. The LevelMind@JC project established an early intervention platform of community‐based ...youth‐specific mental health centres involving youth workers, cross‐disciplinary professionals, and young people. The project intends to (1) pilot a community platform that incorporates a youth‐friendly early screening tool with preventative intervention capabilities, (2) set up a state‐of‐the‐art training system for youth mental health workers, (3) establish a community clinical support team and (4) develop a timely evaluation system to monitor the service and evaluate its outcome and cost‐effectiveness against generic youth services.
Methods
Six hundred LevelMind@JC service users will be assessed alongside 600 young people visiting generic youth centres and 100 young people in the community. Participants will be matched according to age, gender, years of education, socioeconomic status, and level of distress. Assessments, administered at baseline and at 3, 6 and 12 months, will cover demographic characteristics, psychological distress, quality of life, depressive and anxiety symptoms, functioning, physical health and lifestyle, personality and social measures, cognitive measures and health economics. Mixed‐model ANOVAs will be used to indicate interactions between services and between time points.
Conclusion
Built upon a community‐based support model, LevelMind@JC aims to promote positive mental health in young people through the collaboration of cross‐disciplinary mental health professionals. If efficacy and cost‐effectiveness are established, the project could be scaled up, implicating a wider reach of care. We anticipate its success to be critical in combatting mental health issues stemming from both personal and population‐level stressors.
Thioamides antithyroid‐drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD‐induced agranulocytosis is important for clinical management. ...We performed a genome‐wide association study (GWAS) involving 20 patients with ATD‐induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single‐nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD‐induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8–103.7; P = 1.3 × 10‐24) and replication (OR = 37; 95% CI = 3.7–367.4; P = 9.6 × 10‐7). HLA‐B*38:02:01 was in complete linkage disequilibrium with rs185386680. High‐resolution HLA typing confirmed that HLA‐B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)‐induced agranulocytosis (OR = 265.5; 95% CI = 27.9–2528.0; P = 2.5 × 10‐14), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA‐B*38:02:01 in predicting CMZ/MMI‐induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.
Abstract
Aims
Brief measurements of the subjective experience of stress with good predictive capability are important in a range of community mental health and research settings. The potential for ...large-scale implementation of such a measure for screening may facilitate early risk detection and intervention opportunities. Few such measures however have been developed and validated in epidemiological and longitudinal community samples. We designed a new single-item measure of the subjective level of stress (SLS-1) and tested its validity and ability to predict long-term mental health outcomes of up to 12 months through two separate studies.
Methods
We first examined the content and face validity of the SLS-1 with a panel consisting of mental health experts and laypersons. Two studies were conducted to examine its validity and predictive utility. In study 1, we tested the convergent and divergent validity as well as incremental validity of the SLS-1 in a large epidemiological sample of young people in Hong Kong (
n
= 1445). In study 2, in a consecutively recruited longitudinal community sample of young people (
n
= 258), we first performed the same procedures as in study 1 to ensure replicability of the findings. We then examined in this longitudinal sample the utility of the SLS-1 in predicting long-term depressive, anxiety and stress outcomes assessed at 3 months and 6 months (
n
= 182) and at 12 months (
n
= 84).
Results
The SLS-1 demonstrated good content and face validity. Findings from the two studies showed that SLS-1 was moderately to strongly correlated with a range of mental health outcomes, including depressive, anxiety, stress and distress symptoms. We also demonstrated its ability to explain the variance explained in symptoms beyond other known personal and psychological factors. Using the longitudinal sample in study 2, we further showed the significant predictive capability of the SLS-1 for long-term symptom outcomes for up to 12 months even when accounting for demographic characteristics.
Conclusions
The findings altogether support the validity and predictive utility of the SLS-1 as a brief measure of stress with strong indications of both concurrent and long-term mental health outcomes. Given the value of brief measures of mental health risks at a population level, the SLS-1 may have potential for use as an early screening tool to inform early preventative intervention work.
Restrictive COVID-19 measures can have significant mental health impacts, particularly on young people. How such measures may influence day-to-day momentary affect, nonetheless, remains to be ...explored. Experience sampling data were collected from 165 young people (aged 15–24) as part of a larger epidemiological youth mental health study in Hong Kong. We examined the impact of one of the most stringent COVID-19 measures – dine-in restrictions – on momentary positive and negative affect and current contexts and activities of these young people. The effects of a milder form of COVID-19 measure – school suspension – were separately examined. Multilevel analysis revealed that those in the dine-in ban group, compared to dining-as-usual, showed significantly reduced momentary positive affect (
β
= −0.17,
SE
= 0.06,
p
= 0.003). Its effect remained significant even when accounting for baseline depressive and anxiety symptoms and socioeconomic status (
β
= −0.15,
SE
= 0.05,
p
= 0.008). The effect of dine-in ban on reduced momentary positive affect was found specifically when participants were in indoor locations (e.g., home, office), alone, and engaged in passive leisure activities. This pattern was not observed when participants were at school or at other outdoor locations, with friends, or engaged in active leisure activities. No significant effect of school suspension on momentary affect was observed. More severe COVID-19 measures, such as dine-in ban, can have significant impacts on the momentary positive affect of young people. Certain contexts and activities may offer protection against the consequences of COVID-19 measures. The current findings may help to inform future designs of mental health interventions and public health policies.
Spiral twisting offers additional opportunities for controlling the loss, dispersion, and polarization state of light in optical fibers with noncircular guiding cores. Here, we report an effect that ...appears in continuously twisted photonic crystal fiber. Guided by the helical lattice of hollow channels, cladding light is forced to follow a spiral path. This diverts a fraction of the axial momentum flow into the azimuthal direction, leading to the formation of discrete orbital angular momentum states at wavelengths that scale linearly with the twist rate. Core-guided light phase-matches topologically to these leaky states, causing a series of dips in the transmitted spectrum. Twisted photonic crystal fiber has potential applications in, for example, band-rejection filters and dispersion control.
Swelling kinetics of superabsorbent polymers (SAP) in fresh concrete is complex, but its understanding is crucial for optimisation in practical applications. In this study, the effect of ...concentration of ions common in pore solution (Na+, K+, Ca2+, Cl−, OH−, SO42−) and cyclic wetting/drying on the swelling and ionic exchange of poly(AA) and poly(AA-co-AM) were investigated. Results show that swelling is not a simple function of concentration or ionic strength. In cement paste, SAP absorbs Ca2+ and releases its counterion (Na+, K+) into pore solution. Ca2+ binds with SAP and decreases initial swelling, but the bound Ca2+ can be displaced and swelling gradually recovers. Swelling increases with increase in alkalinity, but decreases with increase in calcium concentration. The higher the degree of ion exchange, the lower the swelling of SAP. Poly(AA) is more susceptible to Ca2+ complexation and therefore achieves a lower swelling ratio and slower swelling recovery compared to poly(AA-co-AM).
A number of studies have demonstrated that various components of the ATRX/DAXX/Histone H3.3 complex are important for heterochromatin silencing at multiple genomic regions. We provide an overview of ...the individual components (ATRX, DAXX and/or H3.3) tested in each study and propose a model where the ATRX/DAXX chaperone complex deposits H3.3 to maintain the H3K9me3 modification at heterochromatin throughout the genome.
Objectives:
The co-occurrence of different classes of population-level stressors, such as social unrest and public health crises, is common in contemporary societies. Yet, few studies explored their ...combined mental health impact. The aim of this study was to examine the impact of repeated exposure to social unrest-related traumatic events (TEs), coronavirus disease 2019 (COVID-19) pandemic-related events (PEs), and stressful life events (SLEs) on post-traumatic stress disorder (PTSD) and depressive symptoms, and the potential mediating role of event-based rumination (rumination of TEs-related anger, injustice, guilt, and insecurity) between TEs and PTSD symptoms.
Methods:
Community members in Hong Kong who had utilized a screening tool for PTSD and depressive symptoms were invited to complete a survey on exposure to stressful events and event-based rumination.
Results:
A total of 10,110 individuals completed the survey. Hierarchical regression analysis showed that rumination, TEs, and SLEs were among the significant predictors for PTSD symptoms (all P < 0.001), accounting for 32% of the variance. For depression, rumination, SLEs, and PEs were among the significant predictors (all P < 0.001), explaining 24.9% of the variance. Two-way analysis of variance of different recent and prior TEs showed significant dose-effect relationships. The effect of recent TEs on PTSD symptoms was potentiated by prior TEs (P = 0.005). COVID-19 PEs and prior TEs additively contributed to PTSD symptoms, with no significant interaction (P = 0.94). Meanwhile, recent TEs were also potentiated by SLEs (P = 0.002). The effects of TEs on PTSD symptoms were mediated by rumination (β = 0.38, standard error = 0.01, 95% confidence interval: 0.36 to 0.41), with 40.4% of the total effect explained. All 4 rumination subtypes were significant mediators.
Conclusions:
Prior and ongoing TEs, PEs, and SLEs cumulatively exacerbated PTSD and depressive symptoms. The role of event-based rumination and their interventions should be prioritized for future research.
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