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Patient involvement enhances transparency, legitimacy, and responsiveness in pharmaceutical reimbursement decisions. Guided by the mosaic model, this study recognizes effective patient engagement requires diverse context-specific approaches. Despite Taiwan’s National Health Insurance Administration (NHIA) implementing policies, gaps remain between intent and practice. This study evaluates NHIA’s incorporation of patient inputs into reimbursement decisions and examines factors influencing involvement.
Methods
We analyzed pharmaceutical company-initiated reimbursement submissions for catastrophic illnesses reviewed by the Pharmaceutical Benefit and Reimbursement Scheme Joint Committee (PBRS) from 2016 to 2023. Data sources included PBRS meeting records, the Online Patient Opinion Platform (OPOP), and NHIA notification E-mails. Generalized linear models identified predictors of patient involvement. The association between patient involvement and PBRS decisions was also explored.
Results
Patient involvement occurred in 28.4 percent (80/282) of all submissions, increasing from 17 percent (2016) to 44 percent (2023). Despite aligning with OPOP criteria, patient involvement remained incomplete. Discussion-type submissions, oncology drugs, and new drug applications showed higher involvement, whereas autoimmune diseases and new indication submissions had lower involvement. Budget impact and innovation categories were not significant predictors in adjusted models. The presence of patient involvement was not significantly associated with the PBRS approval rate. Ad hoc analysis revealed increased involvement for new indications following policy expansion.
Conclusions
Despite NHIA’s efforts, patient involvement implementation remains suboptimal. Structured mechanisms and expanded patient involvement beyond high-profile submissions and PBRS are crucial to broaden patient involvement. This study provides practical insights for East Asian healthcare systems advancing patient involvement amid limited empirical research.
Tuberculosis (TB) remains a significant public health concern in China. Using data from the Global Burden of Disease (GBD) study 2021, we analyzed trends in age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and disability-adjusted life years (DALYs) for TB from 1990 to 2021. Over this period, HIV-negative TB showed a marked decline in ASIR (AAPC = −2.34%, 95% CI: −2.39, −2.28) and ASMR (AAPC = −0.56%, 95% CI: −0.62, −0.59). Specifically, drug-susceptible TB (DS-TB) showed reductions in both ASIR and ASMR, while multidrug-resistant TB (MDR-TB) showed slight decreases. Conversely, extensively drug-resistant TB (XDR-TB) exhibited upward trends in both ASIR and ASMR. TB co-infected with HIV (HIV-DS-TB, HIV-MDR-TB, HIV-XDR-TB) showed increasing trends in recent years. The analysis also found an inverse correlation between ASIRs and ASMRs for HIV-negative TB and the Socio-Demographic Index (SDI). Projections from 2022 to 2035 suggest continued increases in ASIR and ASMR for XDR-TB, HIV-DS-TB, HIV-MDR-TB, and HIV-XDR-TB. The rising burden of XDR-TB and HIV-TB co-infections presents ongoing challenges for TB control in China. Targeted prevention and control strategies are urgently needed to mitigate this burden and further reduce TB-related morbidity and mortality.
The extracellular matrices, such as the haemolymph, in insects are at the centre of most physiological processes and are protected from oxidative stress by the extracellular antioxidant enzymes. In this study, we identified two secreted superoxide dismutase genes (PxSOD3 and PxSOD5) and investigated the oxidative stress induced by chlorpyrifos (CPF) in the aquatic insect Protohermes xanthodes (Megaloptera: Corydalidae). PxSOD3 and PxSOD5 contain the signal peptides at the N-terminus. Structure analysis revealed that PxSOD3 and PxSOD5 contain the conserved CuZn-SOD domain, which is mainly composed of β-sheets and has conserved copper and zinc binding sites. Both PxSOD3 and PxSOD5 are predicted to be soluble proteins located in the extracellular space. After exposure to different concentrations of sublethal CPF, MDA content in P. xanthodes larvae were increased in a dose-dependent manner; SOD and CAT activities were also higher in CPF-treated groups than that in the no CPF control, indicating that sublethal CPF induces oxidative stress in P. xanthodes larvae. Furthermore, PxSOD3 and PxSOD5 expression levels and haemolymph SOD activity in the larvae were downregulated by sublethal CPF at different concentrations. Our results suggest that the PxSOD3 and PxSOD5 are putative extracellular antioxidant enzymes that may play a role in maintaining the oxidative balance in the extracellular space. Sublethal CPF may induce oxidative stress in the extracellular space of P. xanthodes by reducing the gene expression and catalytic activity of extracellular SODs.
This paper presents a low-profile miniaturized dual-band antenna utilizing the quarter-mode substrate integrated waveguide (QMSIW) structure. The two modes of TE110 and TE220 of a single QMSIW structure are employed, enabling a dual-band operation. The frequency ratio between the two bands can be tuned by loading a capacitive structure, which is comprised of a capacitive-loaded patch and a short circuit post, inside the QMSIW structure. By introducing parasitic QMSIW structures through magnetic coupling, a dual-band antenna with enhanced bandwidths is achieved. The antenna has dimensions of smaller than 400 mm2 (0.048λL2) with a uniform height of 1.4 mm (0.016λL). Measurement results indicate that the −6 dB impedance bandwidths of the antennas can cover the 5G N78 (3.3–3.6 GHz) and N79 (4.8–5 GHz) bands, and the average efficiencies is better than −2.5 dB. To the authors’ knowledge, the proposed designs offer dual-wideband operation while having the smallest planar dimension compared to the previously reported antennas. Furthermore, an extended electric coupling dual-band antenna configuration is also described and measured, which achieves similar bandwidth extension as the proposed antenna.
History effects play a significant role in determining the velocity in boundary layers with pressure gradients, complicating the identification of a velocity scaling. This work pivots away from traditional velocity analysis to focus on fluid acceleration in boundary layers with strong adverse pressure gradients. We draw parallels between the transport equation of the velocity in an equilibrium spatially evolving boundary layer and the transport equation of the fluid acceleration in temporally evolving boundary layers with pressure gradients, establishing an analogy between the two. To validate our analogy, we show that the laminar Stokes solution, which describes the flow immediately after the application of a pressure gradient force, is consistent with the present analogy. Furthermore, fluid acceleration exhibits a linear scaling in the wall layer and transitions to logarithmic scaling away from the wall after the initial period, mirroring the velocity in an equilibrium boundary layer, lending further support to the analogy. Finally, by integrating fluid acceleration, a velocity scaling is derived, which compares favourably with data as well.
The cumulative effects of long-term exposure to pandemic-related stressors and the severity of social restrictions may have been important determinants of mental distress in the time of COVID-19.
Aim
This study aimed to investigate mental health among a cohort of Chinese university students over a 28-month period, focusing on the effects of lockdown type.
Methods
Depression, anxiety, stress and fear of COVID-19 infection were measured ten times among 188 Chinese students (females 77.7%, meanage = 19.8, s.d.age = 0.97), every 3 months: from prior to the emergence of COVID-19 in November 2019 (T1) to March 2022 (T10).
Results
Initially depression, anxiety and stress dipped from T1 to T2, followed by a sudden increase at T3 and a slow upward rise over the remainder of the study period (T3 to T10). When locked down at university, participants showed greater mental distress compared with both home lockdown (d = 0.35–0.48) and a no-lockdown comparison period (d = 0.28–0.40). Conversely, home lockdown was associated with less anxiety and stress (d = 0.19 and 0.21, respectively), but not with depression (d = 0.13) compared with a no-lockdown period.
Conclusions
This study highlights the cumulative effects of exposure to COVID-19 stressors over time. It also suggests that the way in which a lockdown is carried out can impact the well-being of those involved. Some forms of lockdown appear to pose a greater threat to mental health than others.
In this article, motivated by the regularity theory of the solutions of doubly nonlinear parabolic partial differential equations, the authors introduce the off-diagonal two-weight version of the parabolic Muckenhoupt class with time lag. Then the authors introduce the uncentered parabolic fractional maximal operator with time lag and characterize its two-weighted boundedness (including the endpoint case) in terms of these weights under an additional mild assumption (which is not necessary for one-weight case). The most novelty of this article exists in that the authors further introduce a new parabolic shaped domain and its corresponding parabolic fractional integral with time lag and, moreover, applying the aforementioned (two-)weighted boundedness of the parabolic fractional maximal operator with time lag, the authors characterize the (two-)weighted boundedness (including the endpoint case) of these parabolic fractional integrals in terms of the off-diagonal (two-weight) parabolic Muckenhoupt class with time lag; as applications, the authors further establish a parabolic weighted Sobolev embedding and a priori estimate for the solution of the heat equation. The key tools to achieve these include the parabolic Calderón–Zygmund-type decomposition, the chaining argument, and the parabolic Welland inequality, which is obtained by making the utmost of the geometrical relation between the parabolic shaped domain and the parabolic rectangle.
Despite growing awareness of the mental health damage caused by air pollution, the epidemiologic evidence on impact of air pollutants on major mental disorders (MDs) remains limited. We aim to explore the impact of various air pollutants on the risk of major MD.
Methods
This prospective study analyzed data from 170 369 participants without depression, anxiety, bipolar disorder, and schizophrenia at baseline. The concentrations of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5), particulate matter with aerodynamic diameter > 2.5 μm, and ≤ 10 μm (PM2.5–10), nitrogen dioxide (NO2), and nitric oxide (NO) were estimated using land-use regression models. The association between air pollutants and incident MD was investigated by Cox proportional hazard model.
Results
During a median follow-up of 10.6 years, 9 004 participants developed MD. Exposure to air pollution in the highest quartile significantly increased the risk of MD compared with the lowest quartile: PM2.5 (hazard ratio [HR]: 1.16, 95% CI: 1.09–1.23), NO2 (HR: 1.12, 95% CI: 1.05–1.19), and NO (HR: 1.10, 95% CI: 1.03–1.17). Subgroup analysis showed that participants with lower income were more likely to experience MD when exposed to air pollution. We also observed joint effects of socioeconomic status or genetic risk with air pollution on the MD risk. For instance, the HR of individuals with the highest genetic risk and highest quartiles of PM2.5 was 1.63 (95% CI: 1.46–1.81) compared to those with the lowest genetic risk and lowest quartiles of PM2.5.
Conclusions
Our findings highlight the importance of air pollution control in alleviating the burden of MD.
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.
The spatio-temporal scales, as well as a comprehensive self-sustained mechanism of the reattachment unsteadiness in shock wave/boundary layer interaction, are investigated in this study. Direct numerical simulations reveal that the reattachment unsteadiness of a Mach 7.7 laminar inflow causes over $26\,\%$ variation in wall friction and up to $20\,\%$ fluctuation in heat flux at the reattachment of the separation bubble. A statistical approach, based on the local reattachment upstream movement, is proposed to identify the spanwise and temporal scales of reattachment unsteadiness. It is found that two different types, i.e. self-induced and random processes, dominate different regions of reattachment. A self-sustained mechanism is proposed to comprehend the reattachment unsteadiness in the self-induced region. The intrinsic instability of the separation bubble transports vorticity downstream, resulting in an inhomogeneous reattachment line, which gives rise to baroclinic production of quasi-streamwise vortices. The pairing of these vortices initiates high-speed streaks and shifts the reattachment line upstream. Ultimately, viscosity dissipates the vortices, triggering instability and a new cycle of reattachment unsteadiness. The temporal scale and maximum vorticity are estimated with the self-sustained mechanism via order-of-magnitude analysis of the enstrophy. The advection speed of friction, derived from the assumption of coherent structures advecting with a Blasius-type boundary layer, aligns with the numerical findings.
Purple nutsedge (Cyperus rotundus L.) is one of the world’s resilient upland weeds, primarily spreading through its tubers. Its emergence in rice (Oryza sativa L.) fields has been increasing, likely due to changing paddy-farming practices. This study aimed to investigate how C. rotundus, an upland weed, can withstand soil flooding and become a problematic weed in rice fields. The first comparative analysis focused on the survival and recovery characteristics of growing and mature tubers of C. rotundus exposed to soil-flooding conditions. Notably, mature tubers exhibited significant survival and recovery abilities in these environments. Based on this observation, further investigation was carried out to explore the morphological structure, nonstructural carbohydrates, and respiratory mechanisms of mature tubers in response to prolonged soil flooding. Over time, the mature tubers did not form aerenchyma but instead gradually accumulated lignified sclerenchymal fibers, with lignin content also increasing. After 90 d, the lignified sclerenchymal fibers and lignin contents were 4.0 and 1.1 times higher than those in the no soil-flooding treatment. Concurrently, soluble sugar content decreased while starch content increased, providing energy storage, and alcohol dehydrogenase activity rose to support anaerobic respiration via alcohol fermentation. These results indicated that mature tubers survived in soil-flooding conditions by adopting a low-oxygen quiescence strategy, which involves morphological adaptations through the development of lignified sclerenchymal fibers, increased starch reserves for energy storage, and enhanced anaerobic respiration. This mechanism likely underpins the flooding tolerance of mature C. rotundus tubers, allowing them to endure unfavorable conditions and subsequently germinate and grow once flooding subsides. This study provides a preliminary explanation of the mechanism by which mature tubers of C. rotundus from the upland areas confer flooding tolerance, shedding light on the reasons behind this weed’s increasing presence in rice fields.
The mean flow in a turbulent boundary layer (TBL) deviates from the canonical law of the wall (LoW) when influenced by a pressure gradient. Consequently, LoW-based near-wall treatments are inadequate for such flows. Chen et al. (J. Fluid Mech., vol. 970, 2023, A3) derived a Navier–Stokes-based velocity transformation that accurately describes the mean flow in TBLs with arbitrary pressure gradients. However, this transformation requires information on total shear stress, which is not always readily available, limiting its predictive power. In this work, we invert the transformation and develop a predictive near-wall model. Our model includes an additional transport equation that tracks the Lagrangian integration of the total shear stress. Particularly noteworthy is that the model introduces no new parameters and requires no calibration. We validate the developed model against experimental and computational data in the literature, and the results are favourable. Furthermore, we compare our model with equilibrium models. These equilibrium models inevitably fail when there are strong pressure gradients, but they prove to be sufficient for boundary layers subjected to weak, moderate and even moderately high pressure gradients. These results compel us to conclude that history effects in mean flow, which negatively impact the validity of equilibrium models, can largely be accounted for by the material time derivative term and the pressure gradient term, both of which require no additional modelling.
In the contemporary maritime industry, characterised by intense competition, reduced visibility due to heavy fog is a primary cause of accidents, significantly impairing maritime operational efficiency. Consequently, investigating foggy weather navigation safety holds crucial practical significance. This paper, through an analysis and synthesis of various aspects of foggy navigation technology, including foggy navigation regulations at different ports, fog warnings, foggy vessel environmental perception and foggy auxiliary navigation systems, explores the key issues concerning vessel navigation during foggy conditions from a scientific perspective. This discussion encompasses the aspects of regulatory frameworks, standardisation, and the development of intelligent and responsive onboard equipment. Finally, the paper offers a glimpse into potential strategies for fog navigation.
A primary objective of integral methods, such as the momentum integral method, is to discern the physical processes contributing to skin friction. These methods encompass the momentum, kinetic energy and angular momentum integrals. This paper reformulates existing integrals based on the double-averaged Navier–Stokes equations, and extends their application to flows over rough walls. Our derivation yields distinct decompositions for the bottom-wall viscous friction coefficient, denoted as $C_S$, and the roughness element drag coefficient $C_R$. The decompositions comprise three terms: a viscous term, a turbulent term and a roughness (dispersive) term – regardless of the flow configuration, be it channel or boundary layer. Notably, when these integrals are evaluated for laminar flow scenarios, only the viscous term remains significant. In addition, we elucidate the spatial distributions of the terms within these decompositions. To demonstrate the practicality of our formulations, we apply them to analyse data from direct numerical simulations of turbulent half-channel flows. These flows feature aligned and staggered cubical roughness at various packing densities. Our analyses, based on kinetic-energy-oriented decompositions, reveal that when the surface coverage density $\lambda _p$ is small, the dominant terms within the decompositions are the viscous and turbulent terms. With increasing $\lambda _p$, the viscous dissipation term decreases, while the turbulent production term increases and then decreases. These variations arise from a subdued near-wall cycle and the development of a shear layer at the height of the cubes.
Power scaling in conventional broad-area (BA) lasers often leads to the operation of higher-order lateral modes, resulting in a multiple-lobe far-field profile with large divergence. Here, we report an advanced sawtooth waveguide (ASW) structure integrated onto a wide ridge waveguide. It strategically enhances the loss difference between higher-order modes and the fundamental mode, thereby facilitating high-power narrow-beam emission. Both optical simulations and experimental results illustrate the significant increase in additional scattering loss of the higher-order modes. The optimized ASW lasers achieve an impressive output power of 1.1 W at 4.6 A at room temperature, accompanied by a minimal full width at half maximum lateral divergence angle of 4.91°. Notably, the far-field divergence is reduced from 19.61° to 11.39° at the saturation current, showcasing a remarkable 42% improvement compared to conventional BA lasers. Moreover, the current dependence of divergence has been effectively improved by 38%, further confirming the consistent and effective lateral mode control capability offered by our design.
OBJECTIVES/GOALS: Incomplete mucosal healingand dysbiosis prevent long-term remission after colitis. IL4 may restore colon homeostasis through its action on immune cells and the microbiome. We will demonstrate this mechanism using genetically modified mice and molecular tools. This may result in target therapies that prolong remission in patients with IBD. METHODS/STUDY POPULATION: Mice were treated with 3% dextran sulfate sodium (DSS) in drinking water for 5 days to induce colitis. Mice were monitored daily for changes in body weight, and to monitor colitis severity. At each endpoint, mice were sacrificed and colon length was measured. For disease severity assessment, mouse colons were prepared in paraffin sections by the 'swiss-rolling' method. For flow cytometry, lamina propria mononuclear cell isolation was performed and cellular populations were stained with fluorophore-conjugated antibodies. IL4-eGFP-expressing (4get) mice were used to analyze the cellular expression of IL4 after colitis. Cell-specific IL4 deletion mice were generated using the cre-lox system. RESULTS/ANTICIPATED RESULTS: IL4-deficient mice had worse colitis compared with wild-type controls. Flow cytometry of lamina propria cells from 4get mice showed that most IL4-producing cells after colitis are eosinophils (CD11b+SiglecF+). Flow cytometry of C57bl6 mice showed an influx of IL4Ra+ monocytes (CD11b+Ly6C+) and macrophages (CD11b+F480+). IL4-stimulated bone marrow-derived macrophages demonstrated an increase in HB-EGF mRNA transcription. Myeloid-specific IL4R deleted mice had no difference in colitis severity compared with controls. Neutrophil-specific IL4R-deleted mice had increased colitis severity and mortality. Co-housing of littermate mice rescued recovery after DSS in IL4 deficient mice. DISCUSSION/SIGNIFICANCE: IL4 appears to play a role in restoring homeostasis after colitis. The mechanism depends on eosinophil-derived IL4, and action through neutrophils. However, the reparative function of IL4 can be shared with deficient mice through the microbiome. I will study the cellular and microbial mechanism by which IL4 restores homeostasis after colitis.
The venous blood test is a prevalent auxiliary medical diagnostic method. Venous blood collection equipment can improve blood collection’s success rate and stability, reduce the workload of medical staff, and improve the efficiency of diagnosis and treatment. This study proposed a rigid-flexible composite puncture (RFCP) strategy, based on which a small 7-degree-of-freedom (DOF) auxiliary venipuncture blood collection (VPBC) robot using a trocar needle was designed. The robot consists of a position and orientation adjustment mechanism and a RFCP end-effector, which can perform RFCP to avoid piercing the blood vessel’s lower wall during puncture. The inverse kinematics solution and validation of the robot were analyzed based on the differential evolution algorithm, after which the quintic polynomial interpolation algorithm was applied to achieve the robot trajectory planning control. Finally, the VPBC robot prototype was developed for experiments. The trajectory planning experiment verified the correctness of the inverse kinematics solution and trajectory planning, and the composite puncture blood collection experiment verified the feasibility of the RFCP strategy.