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Patients with chronic insomnia are characterized by alterations in default mode network and alpha oscillations, for which the medial parietal cortex (MPC) is a key node and thus a potential target for interventions.
Methods
Fifty-six adults with chronic insomnia were randomly assigned to 2 mA, alpha-frequency (10 Hz), 30 min active or sham transcranial alternating current stimulation (tACS) applied over the MPC for 10 sessions completed within two weeks, followed by 4- and 6-week visits. The connectivity of the dorsal and ventral posterior cingulate cortex (vPCC) was calculated based on resting functional MRI.
Results
For the primary outcome, the active group showed a higher response rate (≥ 50% reduction in Pittsburgh Sleep Quality Index (PSQI)) at week 6 than that of the sham group (71.4% versus 3.6%) (risk ratio 20.0, 95% confidence interval 2.9 to 139.0, p = 0.0025). For the secondary outcomes, the active therapy induced greater and sustained improvements (versus sham) in the PSQI, depression (17-item Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale), and cognitive deficits (Perceived Deficits Questionnaire-Depression) scores. The response rates in the active group decreased at weeks 8–14 (42.9%–57.1%). Improvement in sleep was associated with connectivity between the vPCC and the superior frontal gyrus and the inferior parietal lobe, whereas vPCC-to-middle frontal gyrus connectivity was associated with cognitive benefits and vPCC-to-ventromedial prefrontal cortex connectivity was associated with alleviation in rumination.
Conclusions
Targeting the MPC with alpha-tACS appears to be an effective treatment for chronic insomnia, and vPCC connectivity represents a prognostic marker of treatment outcome.
In this study, we use a novel design to test for directional behavioral spillover and cognitive load effects in a set of multiple repeated games. Specifically, in our experiment, each subject plays a common historical game with two different matches for 100 rounds. After 100 rounds, the subject switches to a new game with one match and continues playing the historical game with the other match. This design allows us to identify the direction of any behavioral spillover. Our results show that participants exhibit both behavioral spillover and cognitive load effects. First, for pairs of Prisoners’ Dilemma and Alternation games, we find that subjects apply strategies from the historical game when playing the new game. Second, we find that those who participate in a Self Interest game as either their historical or new game achieve Pareto efficient outcomes more often in the Prisoners’ Dilemma and Alternation games compared to their control counterparts. Overall, our results show that, when faced with a new game, participants use strategies that reflect both behavioral spillover and cognitive load effects.
Inclisiran is approved in Singapore as an add-on to maximally tolerated statins for the treatment of primary hypercholesterolemia or mixed dyslipidemia. This study evaluated the cost effectiveness of inclisiran compared with standard care (SC), evolocumab, or alirocumab to treat primary hypercholesterolemia and mixed dyslipidemia.
Methods
A lifetime Markov model was used to evaluate the cost effectiveness of inclisiran as an add-on to SC (inclisiran+SC) versus SC alone, evolocumab+SC, or alirocumab+SC in four subpopulations: atherosclerotic cardiovascular disease (ASCVD), secondary prevention of heterozygous familial hypercholesterolemia (HeFH), primary prevention of HeFH, and primary prevention in patients with an elevated risk of ASCVD Baseline cardiovascular event risks were estimated from databases and published literature from the Netherlands and the UK. Efficacy data were obtained from the ORION trials and other comparative trials. Costs were obtained from public healthcare institutions and local publications. A willingness-to-pay (WTP) threshold of SGD45,000 (USD33,280) per quality-adjusted life-year (QALY) was selected, and a one-way deterministic sensitivity analysis (DSA) was performed.
Results
Inclisiran+SC resulted in higher QALYs and higher total costs than SC alone in all four subpopulations, with incremental cost-effectiveness ratios (ICERs) ranging from SGD34,654 to SGD163,158 (USD25,630 to USD120,673) per QALY gained. At the selected WTP threshold, inclisiran+SC was cost effective, compared with SC, in patients with ASCVD and for secondary prevention of HeFH. Compared with evolocumab+SC and alirocumab+SC, inclisiran+SC achieved higher total QALYs at a lower total cost in all four subpopulations. The ICER was most sensitive to the price and efficacy of inclisiran and the rate ratios translating reductions in low-density lipoprotein cholesterol levels to the risk of cardiovascular death.
Conclusions
Inclisiran+SC resulted in greater QALYs and higher costs, compared with SC alone, and higher QALYs at lower costs, compared with evolocumab+SC and alirocumab+SC, in adults with primary hypercholesterolemia and mixed dyslipidemia. At the selected WTP threshold, inclisiran+SC was cost effective, compared with SC alone, in patients with ASCVD and for secondary prevention of HeFH. These findings can help inform future funding decisions in Singapore.
The immediate priorities for high-power delivery employing solid-core fibers are balancing the nonlinear effect and beam deterioration. Here, the scheme of tapered multimode fiber is experimentally realized. The tapered multimode fiber, featuring a 15 m (24/200 μm)–10 m (tapered region)–80 m (48/400 μm) profile, guides the laser with a weakly coupled condition. With the input power of 1035 W, the maximum output power over the 105 m delivery is 962 W, corresponding to a high efficiency of over 93% and a nonlinear suppression ratio of over 50 dB. Mode resolving results show high-order-mode contents of less than –30 dB in the whole delivery path, resulting in a high-fidelity delivery with M2 factors of 1.20 and 1.23 for the input and output lasers, respectively. Furthermore, the ultimate limits of delivery lengths for solid-core weakly coupled fibers are discussed. This work provides a valuable reference to reconsider the future boom of high-power laser delivery based on solid-core fibers.
A high-energy pulsed vacuum ultraviolet (VUV) solid-state laser at 177 nm with high peak power by the sixth harmonic of a neodymium-doped yttrium aluminum garnet (Nd:YAG) amplifier in a KBe2BO3F2 prism-coupled device was demonstrated. The ultraviolet (UV) pump laser is a 352 ps pulsed, spatial top-hat super-Gaussian beam at 355 nm. A high energy of a 7.12 mJ VUV laser at 177 nm is obtained with a pulse width of 255 ps, indicating a peak power of 28 MW, and the conversion efficiency is 9.42% from 355 to 177 nm. The measured results fitted well with the theoretical prediction. It is the highest pulse energy and highest peak power ever reported in the VUV range for any solid-state lasers. The high-energy, high-peak-power, and high-spatial-uniformity VUV laser is of great interest for ultra-fine machining and particle-size measurements using UV in-line Fraunhofer holography diagnostics.
This study aimed to investigate the effects of esketamine (Esk) combined with dexmedetomidine (Dex) on postoperative delirium (POD) and quality of recovery (QoR) in elderly patients undergoing thoracoscopic radical lung cancer surgery.
Methods
In this prospective, randomized, and controlled study, 172 elderly patients undergoing thoracoscopic radical lung cancer surgery were divided into two groups: the Esk + Dex group (n = 86) and the Dex group a (n = 86). The primary outcome was the incidence of POD within 7 days after surgery and the overall Quality of Recovery−15 (QoR − 15) scores within 3 days after surgery. Secondary outcomes included postoperative adverse reactions, extubation time, PACU stay, and hospitalization time. Serum levels of IL-6, IL-10, S100β protein, NSE, CD3+, CD4+, and CD8+ were detected from T0 to T5.
Results
Compared with the Dex group, the incidence of POD in the Esk + Dex group was significantly lower at 7 days after surgery (14.6% vs 30.9%; P = 0.013). The QoR − 15 score was significantly increased 3 days after surgery (P < 0.01). Levels of IL-6 and CD8+ were significantly decreased, and IL − 10 levels were significantly increased at T1-T2 (P < 0.05). At T1-T4, NSE levels were significantly decreased, while CD3+ and CD4+/CD8+ values were significantly increased (P < 0.01). At T1-T5, serum S100β protein concentration decreased significantly, and CD4+ value increased significantly (P < 0.01). The incidence of nausea/vomiting and hyperalgesia decreased significantly 48 hours after surgery (P < 0.01). The duration of extubation, PACU stay, and postoperative hospitalization were significantly shortened.
Conclusions
Esketamine combined with dexmedetomidine can significantly reduce the POD incidence and improve the QoR in patients undergoing thoracoscopic radical lung cancer surgery, which may be related to the improvement of cellular immune function.
EXOSC10 is an exosome-associated ribonuclease that degrades and processes a wide range of transcripts in the nucleus. The initial segment (IS) of the epididymis is crucial for sperm transport and maturation in mice by affecting the absorption and secretion that is required for male fertility. However, the role of EXOSC10 ribonuclease-mediated RNA metabolism within the IS in the regulation of gene expression and sperm maturation remains unknown. Herein, we established an Exosc10 conditional knockout (Exosc10 cKO) mouse model by crossing Exosc10F/F mice with Lcn9-Cre mice which expressed recombinase in the principal cells of IS as early as post-natal day 17. Morphological and histological analyses revealed that Exosc10 cKO males had normal spermatogenesis and development of IS. Moreover, the sperm concentration, morphology, motility, and frequency of acrosome reactions in the cauda epididymides of Exosc10 cKO mice were comparable with those of control mice. Thus, Exosc10 cKO males had normal fertility. Collectively, our genetic mouse model and findings demonstrate that loss of EXOSC10 in the IS of epididymis is dispensable for sperm maturation and male fertility.
This article presents a dual-band planar microwave sensor to characterize the permittivity of liquid samples. The sensor utilizes a splitter–combiner microstrip segment loaded with two pairs of triangular-shaped complementary split-ring resonators (CSRRs). By integrating a meander slot into the CSRRs and incorporating inter-resonator coupling between the CSRRs, the proposed sensor achieves enhanced frequency shifts, resulting in improved sensitivity. An adulteration detection experiment is conducted to validate the sensor’s performance by mixing mineral oil into castor oil with a polydimethylsiloxane container placed on the sensing area. The variations in resonant frequency and peak attenuation are employed to extract the permittivity of the loaded liquid sample. The peak sensitivities in determining the real permittivity are measured to be 6.34% and 5.7% for the first and second frequency bands, respectively. The measured errors for extracting the real and imaginary parts of the complex permittivity are approximately 3.95% and 7.47% for the first frequency band and 3.67% and 6.28% for the second frequency band, respectively. The proposed dual-band microwave sensor, with its high sensitivity, compact size, small sample volume, and low cost, demonstrates great potential for applications in the quality monitoring of agricultural and industrial products.
This study aims to evaluate the impact of low-carbohydrate diet, balanced dietary guidance and pharmacotherapy on weight loss among individuals with overweight or obesity over a period of 3 months. The study involves 339 individuals with overweight or obesity and received weight loss treatment at the Department of Clinical Nutrition at the Second Affiliated Hospital of Zhejiang University, School of Medicine, between 1 January 2020 and 31 December 2023. The primary outcome is the percentage weight loss. Among the studied patients, the majority chose low-carbohydrate diet as their primary treatment (168 (49·56 %)), followed by balanced dietary guidance (139 (41·00 %)) and pharmacotherapy (32 (9·44 %)). The total percentage weight loss for patients who were followed up for 1 month, 2 months and 3 months was 4·98 (3·04, 6·29) %, 7·93 (5·42, 7·93) % and 10·71 (7·74, 13·83) %, respectively. Multivariable logistic regression analysis identified low-carbohydrate diet as an independent factor associated with percentage weight loss of ≥ 3 % and ≥ 5 % at 1 month (OR = 0·461, P < 0·05; OR = 0·349, P < 0·001). The results showed that a low-carbohydrate diet was an effective weight loss strategy in the short term. However, its long-term effects were comparable to those observed with balanced dietary guidance and pharmacotherapy.
Recent studies of viscous dissipation mechanisms in impacting droplets have revealed distinct behaviours between the macroscale and nanoscale. However, the transition of these mechanisms from the macroscale to the nanoscale remains unexplored due to limited research at the microscale. This work addresses the gap using the many-body dissipative particle dynamics (MDPD) method. While the MDPD method omits specific atomic details, it retains crucial mesoscopic effects, making it suitable for investigating the impact dynamics at the microscale. Through the analysis of velocity contours within impacting droplets, the research identifies three primary contributors to viscous dissipation during spreading: boundary-layer viscous dissipation from shear flow; rim geometric head loss; and bulk viscous dissipation caused by droplet deformation. This prompts a re-evaluation of viscous dissipation mechanisms at both the macroscale and nanoscale. It reveals that the same three kinds of dissipation are present across all scales, differing only in their relative intensities at each scale. A model of the maximum spreading factor (βmax) incorporating all forms of viscous dissipation without adjustable parameters is developed to substantiate this insight. This model is validated against three distinct datasets representing the macroscale, microscale and nanoscale, encompassing a broad spectrum of Weber numbers, Ohnesorge numbers and contact angles. The satisfactory agreement between the model predictions and the data signifies a breakthrough in establishing a universal βmax model applicable across all scales. This model demonstrates the consistent nature of viscous dissipation mechanisms across different scales and underscores the importance of integrating microscale behaviours to understand macroscale and nanoscale phenomena.
Artificial sweeteners are generally used and recommended to alternate added sugar for health promotion. However, the health effects of artificial sweeteners remain unclear. In this study, we included 6371 participants from the National Health and Nutrition Examination Survey with artificial sweetener intake records. Logistic regression and Cox regression were applied to explore the associations between artificial sweeteners and risks of cardiometabolic disorders and mortality. Mendelian randomisation was performed to verify the causal associations. We observed that participants with higher consumption of artificial sweeteners were more likely to be female and older and have above medium socio-economic status. After multivariable adjustment, frequent consumers presented the OR (95 % CI) for hypertension (1·52 (1·29, 1·80)), hypercholesterolaemia (1·28 (1·10, 1·50)), diabetes (3·74 (3·06, 4·57)), obesity (1·52 (1·29, 1·80)), congestive heart failure (1·89 (1·35, 2·62)) and heart attack (1·51 (1·10, 2·04)). Mendelian randomisation confirmed the increased risks of hypertension and type 2 diabetes. Moreover, an increased risk of diabetic mortality was identified in participants who had artificial sweeteners ≥ 1 daily (HR = 2·62 (1·46, 4·69), P = 0·001). Higher consumption of artificial sweeteners is associated with increased risks of cardiometabolic disorders and diabetic mortality. These results suggest that using artificial sweeteners as sugar substitutes may not be beneficial.
Depression is highly prevalent in haemodialysis patients, and diet might play an important role. Therefore, we conducted this cross-sectional study to determine the association between dietary fatty acids (FA) consumption and the prevalence of depression in maintenance haemodialysis (MHD) patients. Dietary intake was assessed using a validated FFQ between December 2021 and January 2022. The daily intake of dietary FA was categorised into three groups, and the lowest tertile was used as the reference category. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression and restricted cubic spline (RCS) models were applied to assess the relationship between dietary FA intake and the prevalence of depression. As a result, after adjustment for potential confounders, a higher intake of total FA [odds ratio (OR)T3 vs. T1 = 1·59, 95 % confidence interval (CI) = 1·04, 2·46] and saturated fatty acids (SFA) (ORT3 vs. T1 = 1·83, 95 % CI = 1·19, 2·84) was associated with a higher prevalence of depressive symptoms. Significant positive linear trends were also observed (P < 0·05) except for SFA intake. Similarly, the prevalence of depression in MHD patients increased by 20% (OR = 1.20, 95% CI = 1.01–1.43) for each standard deviation increment in SFA intake. RCS analysis indicated an inverse U-shaped correlation between SFA and depression (Pnonlinear > 0·05). Additionally, the sensitivity analysis produced similar results. Furthermore, no statistically significant association was observed in the subgroup analysis with significant interaction. In conclusion, higher total dietary FA and SFA were positively associated with depressive symptoms among MHD patients. These findings inform future research exploring potential mechanism underlying the association between dietary FA and depressive symptoms in MHD patients.
Suppressing mode degradation is the key issue for high-power laser delivery; however, diagnosing mode degradation in its entirety, ranging from the contents and origins to locations, has always been a major obstacle. Here, a versatile approach for tracing the origins of mode coupling is demonstrated through addressing the differential intermodal dispersions of fiber modes. Full recognition for modal contents and the origins of mode degradation are experimentally completed in a two-mode fiber laser delivery system, which assists a significant improvement of beam quality M2 from 1.35 to 1.15 at the highest power of over 300 W. This method yields a quantitative characterization for manipulating the individual mode of dual-mode coupling origins or their combinations. This work points toward a promising strategy for the online tracing of mode coupling in cascade fiber links, thus enabling further pursuit of seeking extreme beam quality in high-power fiber laser systems.
Environmental exposures are known to be associated with pathogen transmission and immune impairment, but the association of exposures with aetiology and severity of community-acquired pneumonia (CAP) are unclear. A retrospective observational study was conducted at nine hospitals in eight provinces in China from 2014 to 2019. CAP patients were recruited according to inclusion criteria, and respiratory samples were screened for 33 respiratory pathogens using molecular test methods. Sociodemographic, environmental and clinical factors were used to analyze the association with pathogen detection and disease severity by logistic regression models combined with distributed lag nonlinear models. A total of 3323 CAP patients were included, with 709 (21.3%) having severe illness. 2064 (62.1%) patients were positive for at least one pathogen. More severe patients were found in positive group. After adjusting for confounders, particulate matter (PM) 2.5 and 8-h ozone (O3-8h) were significant association at specific lag periods with detection of influenza viruses and Klebsiella pneumoniae respectively. PM10 and carbon monoxide (CO) showed cumulative effect with severe CAP. Pollutants exposures, especially PM, O3-8h, and CO should be considered in pathogen detection and severity of CAP to improve the clinical aetiological and disease severity diagnosis.
To overcome Yb lasing, a kilowatt-level 1535 nm fiber laser is utilized to in-band pump an Er:Yb co-doped fiber (EYDF) amplifier. The output power of a 301 W narrow-linewidth EYDF amplifier operating at 1585 nm, with 3 dB bandwidth of 150 pm and ${M}^2$< 1.4, is experimentally demonstrated. To the best of our knowledge, it is the highest output power achieved in L-band narrow-linewidth fiber amplifiers with good beam quality. Theoretically, a new ion transition behavior among energy levels for in-band pumping EYDF is uncovered, and a spatial-mode-resolved nonlinearity-assisted theoretical model is developed to understand its internal dynamics. Numerical simulations reveal that the reduction in slope efficiency is significantly related to excited-state absorption (ESA). ESA has a nonlinear hindering effect on power scaling. It can drastically lower the pump absorption and slope efficiency with increasing pump power for in-band pumped EYDF amplifiers. Meanwhile, optimized approaches are proposed to improve its power to the kilowatt level via in-band pumping.
Floating objects will drift due to the action of surface gravity waves. This drift will depart from that of a perfect Lagrangian tracer due to both viscous effects (non-potential flow) and wave–body interaction (potential flow). We examine the drift of freely floating objects in regular (non-breaking) deep-water wave fields for object sizes that are large enough to cause significant diffraction. Systematic numerical simulations are performed using a hybrid numerical solver, qaleFOAM, which deals with both viscosity and wave–body interaction. For very small objects, the model predicts a wave-induced drift equal to the Stokes drift. For larger objects, the drift is generally greater and increases with object size (we examine object sizes up to $10\,\%$ of the wavelength). The effects of different shapes, sizes and submergence depths and steepnesses are examined. Furthermore, we derive a ‘diffraction-modified Stokes drift’ akin to Stokes (Trans. Camb. Phil. Soc., vol. 8, 1847, pp. 411–455), but based on the combination of incident, diffracted and radiated wave fields, which are based on potential-flow theory and obtained using the boundary element method. This diffraction-modified Stokes drift explains both qualitatively and quantitatively the increase in drift. Generally, round objects do not diffract the wave field significantly and do not experience a significant drift enhancement as a result. For box-shape objects, drift enhancement is greater for larger objects with greater submergence depths (we report an increase of $92\,\%$ for simulations without viscosity and $113\,\%$ with viscosity for a round-cornered box whose size is $10\,\%$ of the wavelength). We identify the specific standing wave pattern that arises near the object because of diffraction as the main cause of the enhanced drift. Viscosity plays a small positive role in the enhanced drift behaviour of large objects, increasing the drift further by approximately $20\,\%$.
The Righi–Leduc heat flux generated by the self-generated magnetic field in the ablative Rayleigh–Taylor instability driven by a laser irradiating thin targets is studied through two-dimensional extended-magnetohydrodynamic simulations. The perturbation structure gets into a low magnetization state though the peak strength of the self-generated magnetic field could reach hundreds of teslas. The Righi–Leduc effect plays an essential impact both in the linear and nonlinear stages, and it deflects the total heat flux towards the spike base. Compared to the case without the self-generated magnetic field included, less heat flux is concentrated at the spike tip, finally mitigating the ablative stabilization and leading to an increase in the velocity of the spike tip. It is shown that the linear growth rate is increased by about 10% and the amplitude during the nonlinear stage is increased by even more than 10% due to the feedback of the magnetic field, respectively. Our results reveal the importance of Righi–Leduc heat flux to the growth of the instability and promote deep understanding of the instability evolution together with the self-generated magnetic field, especially during the acceleration stage in inertial confinement fusion.
Binary nanodroplet collisions have received increasing attention, whilst the identification of collision outcomes and the viscous dissipation mechanism have remained poorly understood. Using molecular dynamics simulations, this study investigates binary nanodroplet collisions over wide ranges of Weber number (We), Ohnesorge number (Oh) and off-centre distances. Coalescence, stretching separation and shattering are identified; however, bouncing, reflexive separation and rotational separation reported for millimetre-sized collisions are not observed, which is attributed to the enhanced viscous effect caused by the ‘natural’ high-viscosity characteristics of nanodroplets. Intriguingly, as an intermediate outcome, holes form in retracting films at relatively high We, arising from the vibration and thermal fluctuation of the films. Due to the combined effects of inertial, capillary and viscous forces, binary nanodroplet collisions fall into the cross-over regime, so estimating viscous dissipation becomes extremely important for distinguishing outcome boundaries. Based on the criterion that stretching separation is triggered only when the residual off-centre kinetic energy exceeds the surface energy required for separation, the boundary equation between coalescence and stretching separation is established. Here, viscous dissipation is calculated by the extracted flow feature from simulations, showing that the ratio of viscous dissipation to the initial kinetic energy depends only on Oh, not on We. Because of complex viscous dissipation mechanisms, the same boundary equation in the cross-over regime has also not been satisfactorily revealed for macroscale collisions. Therefore, the proposed equation is tested for wide data sources from both macroscale and nanoscale collisions, and satisfying agreement is achieved, demonstrating the universality of the equation.