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Noonan syndrome is characterised by typical facial features, short stature, CHDs, and other comorbidities, which are caused by germline mutations in genes coding for components of the Ras-mitogen-activated protein kinase pathway. Noonan syndrome is an inherited disease involving multiple systems, but ventricular arrhythmia in Noonan syndrome is rarely reported.
Case summary:
Here we report a 15-year-old patient with leucine zipperlike transcription regulator 1-associated Noonan syndrome, who has CHD (left ventricular hypertrophy with left ventricular outflow tract obstruction), ventricular arrhythmia, bundle branch block, pectus excavatum, costal eversion, scoliosis, myopia, growth retardation, hearing loss, chest tightness, and fatigue. Chest tightness and fatigue are the main reasons for admission of the patient. The patient was treated with spironolactone, empagliflozin, tolasemide, potassium chloride, and bisoprolol. One month after treatment, the patient has no more chest tightness or fatigue. Genetic testing revealed that the patient had a novel heterozygous variant c.313delT (p.trp105Glyfs * 42) mutation in the leucine zipperlike transcription regulator 1. We provide a review of the literature of leucine zipperlike transcription regulator 1 mutations and find that ventricular arrhythmias have been reported in leucine zipperlike transcription regulator 1-related Noonan syndrome.
Discussion:
Our findings expand on the Noonan syndrome phenotype and suggest that mutations in the leucine zipperlike transcription regulator 1 gene are involved in ventricular arrhythmia.
Previous studies revealed structural differences in cerebellar regions between monolinguals and bilinguals. However, the effect of bilingual experiences on cerebellar functional neuroplasticity remains unclear. Using resting-state functional magnetic resonance imaging (fMRI) data, we compared cerebellar functional connectivity (FC) between monolinguals and bilinguals, and then examined how age of second language acquisition (AoA-L2), immersion of L2 (Immersion-L2), proficiency level of L2 (PL-L2) and usage of L2 (Usage-L2) influence cerebellar FC in bilinguals. We found monolinguals exhibited increased FC between lobules VI, VIIIa and superior temporal gyrus. Increased AoA-L2 was related to decreased cerebello-cortical FC involving lobules VI, CrusI and precentral gyrus. Increased Immersion-L2 was associated with decreased cerebello-orbitofrontal FC. Higher PL-L2 corresponded to stronger cerebellar FC with posterior cingulate gyrus. Bilinguals who used L2 more frequently at home exhibited decreased cerebellar FC, while increased social Usage-L2 was associated with increased FC. These findings highlight bilingualism’s impact on cerebellar functional neuroplasticity, shaped by different bilingual experiences.
Precise control of the laser focal position in the relativistic laser–plasma interaction is crucial for electron acceleration, inertial confinement fusion, high-order harmonic generation, etc. However, conventional methods are characterized by limited tunability and rapid divergence of the relativistic laser pulse after passing through a single focal point. In this work, we propose a novel plasma lens with a density gradient to achieve laser focusing in a tunable focal volume. The capacity depends on the modification of the phase velocity of the incident seed laser propagating in plasma. By modifying the plasma density gradient, one can even achieve an off-axis focusing plasma lens, allowing the laser to be focused further at an adjustable focus. Based on this new type of optical device, a beam-splitting array is also proposed to leverage this unique focusing mechanism for the generation of strong axial magnetic fields (>1000 T). Three-dimensional particle-in-cell simulations demonstrate that the seed laser with a focal spot of $9\ \unicode{x3bc} \mathrm{m}$ passing through the density varying plasma lens exhibits a focused laser with a focal spot of approximately $2.3\ \unicode{x3bc} \mathrm{m}$ and an 18 times enhancement of the laser intensity. The approach has considerable potential for applications in several areas, including laser-driven particle acceleration, X/$\gamma$-ray emission, strong magnetic field generation, etc.
How does a CEO’s early-life poverty trauma exposure affect a firm’s involvement in poverty alleviation and the prioritization between generic and strategic involvement? We find that CEOs with such exposure are more likely to engage in both types of poverty alleviation initiatives. We further examine the asymmetry effect and find that these CEOs will prioritize strategic over generic involvement in poverty alleviation. We also conduct a post hoc analysis to test the mediating effect of emphasis on resource efficiency on the relationship between CEOs’ early-life exposure to poverty trauma and the relative emphasis on strategic over generic involvement in poverty alleviation. Using a sample of Chinese publicly listed firms from 2016 to 2021, we find strong support for our predictions. Our study contributes to the literature on CEOs’ early-life experiences and corporate poverty alleviation engagement.
Extant studies on cross-border venture capital (VC) investment predominantly focus on how country-level formal institutions impact the flow of VCs across borders, but the potential role of country-level sentiments in this process has received less attention. Drawing upon the trust literature, we explore how home country political sentiment affects cross-border VC investment. Using data on Chinese VCs’ cross-border investments from 2000 to 2021, we find that home country political sentiment positively affects the amount of cross-border VC investment. Government VC (GVC) and connected VC (through sentiment transmission) positively, while investor managerial team education and investor host country experience (through sentiment suppression) negatively, moderate the influence of home country political sentiment.
This study explores whether DNA methylation (DNAm) mediates the association between lean body mass (LBM) and cognition, as well as whether LBM mediates the association between DNAm and cognition. Based on the data of 59 monozygotic twin pairs, mediation analyses were performed using causal inference test method and mediation analyses. Average causal mediation effect (ACME), average direct effect (ADE), and total effect (TE) were calculated. Among the CpGs associated with LBM, five located within PDGFRB and RP11 genes (ACME: −0.0972−0.0463, |ACME/ADE|: 10.44%−18.30%) negatively mediated the association between LBM and cognition, while one in the PAX2 gene (ACME: 0.3510, |ACME/TE|: 11.84%) positively mediated the association. Besides, the methylation risk score (MRS) of RP11 gene (ACME: −0.0517, |ACME/ADE|: 10.64%) and MRS of all CpGs (ACME: −0.0511, |ACME/ADE|: 10.53%) negatively mediated the association of LBM with cognition. For another, LBM negatively mediated the association between the DNAm level of one CpG within UBXN6 and cognition (ACME: −0.0732, |ACME/TE|: 20.78%), while positively mediated the association between the DNAm level of four CpGs within FOXI2 and cognition (ACME: 0.2812−0.4496, |ACME/TE|: 18.15%−27.29%). It was found the DNAm in PDGFRB, RP11 and PAX2 partially mediates the association between LBM and cognition, and the association between DNAm in UBXN6 and FOXI2 with cognition is also partially mediated by LBM.
Hospital-acquired pneumonia (HAP) represents one of the most common nosocomial infections in intensive care units (ICUs), accounting for 25% of all hospital-acquired infections. While oral care is recommended as a preventive measure, the relationship between standardized oral care practices and HAP incidence remains incompletely characterized.
Objective:
To evaluate the association between oral care practice compliance and HAP incidence in ICU patients, and to identify specific aspects of oral care delivery that influence outcomes.
Methods:
We conducted a prospective mixed-methods observational cohort study from May 2021 across seven ICUs in a tertiary hospital in China. The study utilized a two-phase approach: (1) systematic assessment of oral care implementation through structured observation of nursing staff (n = 58), and (2) prospective evaluation of HAP outcomes in patients (n = 142). Primary outcomes included oral care compliance metrics and HAP incidence. HAP was defined according to standardized clinical criteria and confirmed by two independent physicians.
Results:
Among 142 unique patients, 63 (44.37%) received oral care orders. The oral care completion rate was 61.93%, and the qualification rate was 54.13%. In our analysis, HAP (including both ventilator-associated pneumonia [VAP] and non-ventilator hospital-acquired pneumonia [NVHAP]) occurred in 15/63 (23.81%) patients receiving oral care and 22/79 (27.85%) patients without oral care. Multivariate analysis revealed that incomplete oral care (adjusted OR 2.47, [95% CI, 1.15–4.45], P = 0.009), non-qualified care techniques (adjusted OR 3.17, [95% CI, 1.45–6.35], P = 0.002), and inadequate item qualification (adjusted OR 3.33, [95% CI, 1.47–6.55], P = 0.001) were independently associated with increased HAP risk, after adjusting for confounders. Stratified analysis showed similar associations in both VAP and NVHAP subgroups.
Conclusion:
Our investigation demonstrated that suboptimal oral care practices were associated with increased HAP risk in ICU patients. Implementation of evidence-based standardized protocols and improved adherence strategies may help reduce HAP incidence.
We presented an attosecond-precision timing detector based on linear optics. The minimum measurement floor is 1×10–10 fs2/Hz with only 1 mW input optical power. With this novel technique, the residual dispersion of a 5.2 km fiber link is characterized and precisely compensated. Finally, a comprehensive feedback model has been developed to analyze the noise coupling in a long-distance link stabilization system. The simulation results demonstrate an out-of-loop jitter of merely 359 as, integrated at [1 Hz, 1 MHz], at 1 mW input power per photodetector of our timing detector. Remarkably, the system is capable of maintaining sub-femtosecond precision even at optical power levels as low as 240 nW (for a 5.2 km link length), or link lengths as long as 20 km (with 1 μW optical power), respectively.
Mediation analysis is one of the most popularly used methods in social sciences and related areas. To estimate the indirect effect, the least-squares regression is routinely applied, which is also the most efficient when the errors are normally distributed. In practice, however, real data sets are often non-normally distributed, either heavy-tailed or skewed, so that the least-squares estimators may behave very badly. To overcome this problem, we propose a robust M-estimation for the indirect effect via a general loss function, with a main focus on the Huber loss which is more slowly varying at large values than the squared loss. We further propose a data-driven procedure to select the optimal tuning constant by minimizing the asymptotic variance of the Huber estimator, which is more robust than the least-squares estimator facing outliers and non-normal data, and more efficient than the least-absolute-deviation estimator. Simulation studies compare the finite sample performance of the Huber loss with the existing competitors in terms of the mean square error, the type I error rate, and the statistical power. Finally, the usefulness of the proposed method is also illustrated using two real data examples.
This study aimed to demonstrate the utilization value of 1PN embryos. The 1PN zygotes collected from December 2021 to September 2022 were included in this study. The embryo development, the pronuclear characteristics, and the genetic constitutions were investigated. The overall blastocyst formation and good-quality blastocyst rates in 1PN zygotes were 22.94 and 16.24%, significantly lower than those of 2PN zygotes (63.25 and 50.23%, respectively, P = 0.000). The pronuclear characteristics were found to be correlated with the developmental potential. When comparing 1PN zygotes that developed into blastocysts to those that arrested, the former exhibited a significantly larger area (749.49 ± 142.77 vs. 634.00 ± 119.05, P = 0.000), a longer diameter of pronuclear (29.81 ± 3.08 vs. 27.30 ± 3.00, P = 0.000), and a greater number of nucleolar precursor body (NPB) (11.56 ± 3.84 vs. 7.19 ± 2.73, P = 0.000). Among the tested embryos, the diploidy euploidy rate was significantly higher in blastocysts in comparison with the arrested embryos (66.67 vs. 11.76%, P = 0.000), which was also significantly higher in IVF-1PN blastocysts than in ICSI-1PN blastocysts (75.44 vs. 25.00%, P = 0.001). However, the pronuclear characteristics were not found to be linked to the chromosomal ploidy once they formed blastocysts.
In summary, while the developmental potential of 1PN zygotes is reduced, our study shows that, in addition to the reported pronuclear area and diameter, the number of NPB is also associated with their developmental potential. The 1PN blastocysts exhibit a high diploidy euploidy rate, are recommend to be clinically used post genetic testing, especially for patients who do not have other 2PN embryos available.
The aim of this study was to investigate the antioxidant effect of alpha-lipoic acid (α-LA) in dairy cows and its metabolic mechanism. Thirty Holstein cows weighing 550 ± 25 kg, 200 ± 15 days of lactation and calving 2–3 times were randomly divided into three groups, ten cows in each group. Different doses of α-LA were added based on body weight: 0 (CTL), 30 (LA-L) and 60 (LA-H) mg/kg per head per day; 7 days adaptation period, 30 days formal period. Milk production was recorded daily during the test period. Milk and blood samples were collected on the last day. ELISA kits and automatic biochemical analyser were used to detect the indicators in blood; serum metabolites were detected and analysed by non-target metabolomics. The results of the study showed that the addition of α-LA significantly increased milk yield; blood concentrations for HDL, triglyceride, cortisol and triiodothyronine were significantly elevated; and levels of glutathione reductase and nitric oxide synthase were significantly reduced in LA-L group as compared to CTL group. The concentrations of IL-1β, IL-2, TNF-α, IgG and IgA were significantly higher after supplementation with α-LA. Metabolomics analysis revealed 13 and 15 differential metabolites each in positive or negative modes. Methylmalonic acid levels were significantly higher following α-LA supplementation compared to CTL group, as were D-lactose, D-maltose and oleanolic acid levels in LA-L group. In summary, α-LA can enhance milk production, improve antioxidant capacity and immunity, and is more beneficial for animal production and economic benefits at 30 mg/kg.
The Accidental Republic is a concern for all industrialised countries, and China is no exception. To solve this problem, Workers’ Compensation Insurance (WCI) is a perfect option. The redemption of The Accidental Republic can be understood through the development of WCI. However, little attention has been paid to the development of Chinese WCI. Starting from labour insurance regulations promulgated in 1951, this research explores over 70 years of reform and development of Chinese WCI, explicitly dividing reforms into three phases – establishment and implementation, exploration and practice, and adaptation and formation – that aligned with stages of China’s economic development. Further, the insurance fund performance in the last decade is evaluated by Data envelopment analysis and Malmquist (DEA-Malmquist), through the static and dynamic results, yielding generally average results. Subsequently, five major problems of WCI are identified and discussed and five suggestions offered drawing on international comparison and the national situation. Lastly, the accidental and inevitable aspects of China’s WCI system during the redemption of The Accidental Republic are summarised.
In the present study, we performed direct numerical simulations for a hypersonic turbulent boundary layer over the windward side of a lifting body, the HyTRV model, at Mach number $6$ and attack angle 2$^{\circ }$ to investigate the global and local turbulent features, and evaluate its difference from canonical turbulent boundary layers. By scrutinizing the instantaneous and averaged flow fields, we found that the transverse curvature on the windward side of the HyTRV model induces the transverse opposing pressure gradients that push the flow on both sides towards the windward symmetry plane, yielding significant effects of the azimuthal inhomogeneity and large-scale cross-stream circulations, moderate and azimuthal independent influences of adverse pressure gradient, and negligible impact of the mean flow three-dimensionality. Further inspecting the local turbulent statistics, we identified that the mean and fluctuating velocity become increasingly similar to the highly decelerated turbulent boundary layers over flat plates in that the mean velocity deficit is enhanced, and the outer layer Reynolds stresses are amplified as it approaches the windward symmetry plane, and prove to be self-similar under the scaling of Wei & Knopp (J. Fluid Mech., vol. 958, 2023, A9) for adverse-pressure-gradient turbulent boundary layers. Conditionally averaged Reynolds stresses based on strong sweeping and ejection events demonstrated that the Kelvin–Helmholtz instability of the strong embedded shear layer induced by the large-scale cross-stream circulations is responsible for the turbulence amplification in the outer layer. The strong Reynolds analogy that relates the mean velocity and temperature was refined to incorporate the non-canonical effects, showing considerable improvements in the accuracy of such a formula. On the other hand, the temperature fluctuations are still transported passively, as indicated by their resemblance to the velocity. The conclusions obtained in the present study provide potentially profitable information for turbulent modelling modification for the accurate predictions of skin friction and wall heat transfer.
We report on a high-efficiency, high-power tandem Ho:YAG single-crystal fiber (SCF) laser in-band pumped by a Tm-doped fiber laser at 1907 nm. In addition to the uniform heat distribution resulting from the large surface-to-volume ratio of this fiber-like thin-crystal rod, the long gain region provided by the tandem layout of two SCFs enables high lasing efficiency and power handling capability. More than 100 W output power is achieved at 2.1 μm, corresponding to a slope efficiency of 70.5% and an optical-to-optical efficiency of 67.6%. To the best of our knowledge, this is the highest output power and efficiency ever reported from SCF lasers in the 2-μm spectral range.
The response of airfoils to unsteady disturbances is a classic problem in the aerodynamics field. Many theoretical models have been proposed in the past to predict the unsteady aerodynamic forces of airfoils. However, these theories focused on individual airfoil motions or incoming flow disturbances, while the theoretical models for multiple disturbances still need to be developed. In this study, a theoretical model to predict the aerodynamic force of an oscillating airfoil encountering vertical gust is derived from a linear combination of Theodorsen's and Sears’ theories. Experimental investigations involving a two-dimensional pitching airfoil encountering a sinusoidal vertical gust are carried out to examine the proposed theory. It is found that the theory effectively captures the trends in the unsteady lift of airfoils subjected to dual disturbances. However, it tends to overestimate the lift amplitude. Notably, when a quasi-steady correction is applied to the theory, the prediction accuracy is greatly improved. The theory correction agrees well with experiment at small pitching frequencies, while deviations exist at higher pitching frequencies. The temporal evolution of the flow velocity reveals that the velocity disturbance induced by the coupled disturbance around the airfoil conforms to the linear superposition of the velocities induced by each individual disturbance, consistent with the prediction of the vortex sheet model. As the pitching frequency increases, significant nonlinear effects appear near the trailing edge of the airfoil, which may be one key factor for the disparities between the theoretical predictions and the experimental lift at higher pitching frequencies.
Gust response has consistently been a concern in engineering. Critical theories have been proposed in the past to predict the unsteady lift response of an airfoil experiencing vertical gusts by Atassi, and longitudinal gusts by Greenberg. However, their applicability for an airfoil with non-zero angles of attack still needs clarification. Thus, force measurements are conducted to examine these theories’ validity and quasi-steady corrections are applied to compensate potential disparities between the idealised and real flow conditions. Velocity measurements are performed to scrutinise the effect of gusts on the flow around the airfoil, and subsequently to reveal the underlying mechanism governing the airfoil's response to gust-induced perturbations. In the study, two pitching vanes are arranged upstream to generate periodic vertical and longitudinal gusts, whereas a downstream airfoil with angles of attack of 0–12° is subjected to two gust types. It is found that Greenberg's theory demonstrates superior predictive capability in pre-stall regimes, with the potential for its effectiveness to be expanded to post-stall regimes through theoretical refinements. In contrast, Atassi's theory exhibits significant deviations from experimental outcomes across the measured angles of attack. Nevertheless, a modified version of the theory aligns better with experimental results at small angles of attack, whereas substantial discrepancies persist as the angle of attack increases. In the pre-stall regime, the aerodynamic response of the airfoil to vertical gusts displays a linear correlation with the flow angle near the leading edge. In the post-stall regime, the vertical gust induces dynamic stall of the airfoil. The flow angle has an essential effect on the lift coefficient but it alone is inadequate to dictate the trend of the lift coefficient. The vorticity statistics show that negative vortex circulation strongly correlates with the lift coefficient. Thus, further correction of the theory or a new vortex model can be expected to predict the lift variation.
Sepiolite-based composites have great potential for application as flame-retardant and thermal-insulation material but their application and development are limited by poor mechanical properties. The objective of the present study was to combine polyvinyl alcohol (PVA) and 3-aminopropyltriethoxysilane (KH-550) with sepiolite (Sep) to improve its aerogel strength. A universal testing machine, thermogravimetry, and microcalorimetry were used to investigate the mechanical properties, thermal-stability, and flame-retardant properties, respectively, of aerogels. The results indicated that KH-550 can enhance effectively the mechanical properties and flame retardancy of aerogels. The compressive modulus of PVA/Sep vs KH-550/PVA/Sep aerogel was 209.28 vs. 474.43 kPa, the LOI index changed from 26.4 to 30.4%. The porosity of the aerogels was > 96% and the density was < 0.05 g/cm3. The thermal conductivity remained at between 0.0340 and 0.0390 W/(m·K), and the aerogel could recover to > 85% after a 50% compressive deformation. These data indicated that Sep-based aerogel would act as a flame retardant and a thermal insulating material with excellent mechanical properties.
Hydrophobicity, swellability, and dispersion are important properties for organo-montmorillonites (OMnt) and have yet to be fully characterized for all OMnt configurations. The purpose of the present work was to examine the preparation of OMnt from the reaction of Ca2+-montmorillonite (Ca2+-Mnt) with a high concentration of surfactant and to reveal the relevant properties of hydrophobicity and dispersion of the resultant OMnt. A series of OMnt samples were prepared using a small amount of water and cetyltrimethylammonium bromide (CTAB) with a concentration more than the CTAB critical micelle concentration (CMC). The relationship between OMnt microstructure and the hydrophobicity and swellability properties was investigated in detail. The resulting OMnt samples were characterized using powder X-ray diffraction patterns (XRD), Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric and differential thermogravimetry (TG-DTG), water contact angle tests, swelling indices, and transmission electron microscopy (TEM). The addition of CTAB and water in the OMnt preparation affected the OMnt microstructure and properties. An increase in CTAB concentration led to a more ordered arrangement of cetyltrimethylammonium (CTA+) cations in the interlayer space of the OMnt and a large amount of CTA+ cations on the outer surfaces of the OMnt. The swelling indices and the water contact angles of OMnt samples depended on the distribution of the CTAB surfactant on OMnt and the orientation of the surfactant hydrophilic groups on the inner and on the outer surfaces of OMnt. A maximum swelling index of 39 mL/g in xylene was achieved with an average water contact angle of 62.0° ± 2.0° when the amount of CTAB added was 2 times the cation exchange capacity (CEC) of Mnt and the lowest water to dry Mnt mass ratio was 3 during the preparation of OMnt samples. The platelets of OMnt aggregated together in xylene by electrostatic attraction and by hydrophobic interactions.
The Tuluanshan Formation of the eastern Coastal Range of Taiwan overlies an andesitic core complex presumed to be the source of hydrothermal fluids responsible for the Si- and Mg-rich mineralization of sepiolite and palygorskite (attapulgite) which are found in veins within fissures and in fracture zones of the volcanic rocks of the region. This study was undertaken in order to understand these relationships better by characterizing sepiolite and palygorskite in this Formation and by examining their occurrence and distribution in the Tungho (TH) and Chunjih (CJ) areas. Samples were analyzed using X-ray diffraction (XRD), thermal analysis, Fourier-transform infrared (FTIR) spectroscopy, and petrographic, scanning (SEM), and transmission (TEM) electron microscopic methods. Sepiolite and palygorskite are blocky and earthy-type materials that display fibrous characteristics when viewed using TEM and SEM and occurred alone or with chalcedony in veins. The fibers of blocky sepiolite are commonly intercalated with smectite but the earthy type of sepiolite and palygorskite observed in this study displayed precipitation from fluid enriched in Si, Al, Mg, and minor Fe and depleted in other ions at an earlier stage of offset of the andesitic veins. Continuation of reverse faulting and high shearing stress caused the precipitation of a significant quantity of interlaminated sepiolite. Sepiolite and palygorskite were formed at an earlier stage of fluid interaction relative to smectite in the Tuluanshan Formation.
A local COVID-19 outbreak with two community clusters occurred in a large industrial city, Shaoxing, China, in December 2021 after serial interventions were imposed. We aimed to understand the reason by analysing the characteristics of the outbreak and evaluating the effects of phase-adjusted interventions. Publicly available data from 7 December 2021 to 25 January 2022 were collected to analyse the epidemiological characteristics of this outbreak. The incubation period was estimated using Hamiltonian Monte Carlo method. A well-fitted extended susceptible-exposed-infectious-recovered model was used to simulate the impact of different interventions under various combination of scenarios. There were 387 SARS-CoV-2-infected cases identified, and 8.3% of them were initially diagnosed as asymptomatic cases. The estimated incubation period was 5.4 (95% CI 5.2–5.7) days for all patients. Strengthened measures of comprehensive quarantine based on tracing led to less infections and a shorter duration of epidemic. With a same period of incubation, comprehensive quarantine was more effective in containing the transmission than other interventions. Our findings reveal an important role of tracing and comprehensive quarantine in blocking community spread when a cluster occurred. Regions with tense resources can adopt home quarantine as a relatively affordable and low-impact intervention measure compared with centralized quarantine.