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Organic solvent nanofiltration (OSN) plays important roles in pharmaceutical ingredients purification and solvent recovery. However, the low organic solvent permeance under cross-flow operation of OSN membrane hampers their industrial applications. Herein, we report the construction of coffee-ring structured membrane featuring high OSN permeance. A water-insoluble crystal monomer that dissolved in EtOH/H2O mixed solvent was designed to react with trimesoyl chloride via interfacial polymerization. Owing to the diffusion of EtOH to n-hexane, coffee-ring nanostructure on the support membrane appeared, which served as the template for construction of coffee-ring structured membrane. The optimal nanostructured membrane demonstrated 2.6-fold enhancement in the effective surface area with reduced membrane thickness. Resultantly, the membrane afforded a 2.7-fold enhancement in organic solvent permeance, e.g., ~13â LMH/bar for MeOH, without sacrificing the rejection ability. Moreover, due to the rigid monomer structure, the fabricated membrane shows distinctive running stability in active pharmaceutical ingredients purification and the ability for concentration of medicines.
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Polyimide (PI) films are widely used in electronic devices owing to their excellent mechanical and electrical properties and high thermal and chemical stabilities. In particular, PI films play an important role in flexible printed circuit boards (FPCBs). However, one challenge currently faced with their use is that the adhesives used in FPCBs cause a high dielectric loss in high-frequency applications. Therefore, it is envisioned that PI films with a low dielectric loss and Cu films can be used to prepare two-layer flexible copper-clad laminates (FCCLs) without any adhesive. However, the preparation of ultra-thin FCCLs with no adhesives is difficult owing to the low peel strength between PI films and Cu films. To address this technical challenge, an FCCL with no adhesive was prepared via high-power helicon wave plasma (HWP) treatment. Field-emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) were tested. Also, the surface roughness of the PI film and the peel strength between the PI film and Cu film were measured. The experimental results show that the surface roughness of the PI film increased by 40-65% and the PI film demonstrated improved adhesion (the peel strength was >8.0 N/cm) with the Cu film following plasma treatment and Cu plating.
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Mixed matrix membranes (MMMs), conjugating the advantages of flexible processing-ability of polymers and high-speed mass transfer of porous fillers, are recognized as the next-generation high-performance CO2 capture membranes for solving the current global climate challenge. However, controlling the crystallization of porous metal-organic frameworks (MOFs) and thus the close stacking of MOF nanocrystals in the confined polymer matrix is still undoable, which thus cannot fully utilize the superior transport attribute of MOF channels. In this study, the "confined swelling coupled solvent-controlled crystallization" strategy is employed for well-tailoring the in-situ crystallization of MOF nanocrystals, realizing rapid (<5 min) construction of defect-free freeway channels for CO2 transportation in MMMs due to the close stacking of MOF nanocrystals. Consequently, the fabricated MMMs exhibit approximately fourfold enhancement in CO2 permeability, i.e., 2490 Barrer with a CO2 /N2 selectivity of 37, distinctive antiplasticization merit, as well as long-term running stability, which is at top-tier level, enabling the large-scale manufacture of high-performance MMMs for gas separation.
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Objective: To assess the associations between tobacco use and health care service utilization in Chinese individuals aged more or equal to 40 years old. Method: This research was a cross-sectional study using data from eight provinces in China, and the final sample consisted of 4,733 observations (4,749 participants) aged more or equal to 40 years old. The dependent variable was health care utilization measured by outpatient and inpatient service utilization. Descriptive statistics were used to summarize the socio-demographic characteristics of the sample according to smoking status. The association between tobacco use and health care service utilization was examined by an instrumental variable (IV) probit model. Results: Of the respondents interviewed in 2020, 3,116 (65.84%) were never smokers, 654 (13.82%) were smokers with the smoking index (SI) <400, and 963(20.34%) were smokers with SI≥400. Smokers with SI <400 reported a 6.80% higher probability of using outpatient services. Smokers with SI <400 and SI≥400 reported a 3.10 and 4.20% higher average probability of using ≥3 outpatient visits than never smokers, respectively. Additionally, smokers with SI <400 and SI≥400 reported a 6.30 and 6.20% higher average probability of using inpatient services than those who had not smoked. Moreover, smokers with SI≥400 were more likely to have had ≥2 hospital visits than nonsmokers. Conclusions: Smokers make greater use of health care services. Control of smoking may ease the burden of related health care utilization.
Subject(s)
Cigarette Smoking , Humans , Middle Aged , Adult , Aged , Cross-Sectional Studies , China/epidemiology , Patient Acceptance of Health Care , SmokersABSTRACT
Globally, dyslipidemia is now become a leading risk factor for many adverse health outcomes, especially in the middle-aged and elderly. Recent evidence suggests that exposure to greenness and the relief of a psychological burden may decrease the prevalence of dyslipidemia. The objective of our study was to examine whether a green space can moderate the association between mental health status and dyslipidemia. Our study selected the datasets of depression symptoms, dyslipidemia from the China Health and Retirement Longitudinal Study (CHARLS), and the satellite-based normalized difference vegetation index (NDVI) from the 30 m annual maximum NDVI dataset in China in 2018. Ultimately, a total of 10,022 middle-aged and elderly Chinese were involved in our study. Multilevel logistic regressions were performed to examine the association between symptoms of depression and dyslipidemia, as well as the moderate effect of greenness exposure on the association. Our research suggested that adults diagnosed with depression symptoms were more likely to suffer from dyslipidemia. In addition, the NDVI was shown to moderate the effect of depression on dyslipidemia significantly, though the effect was attenuated as depression increased. Regarding the moderate effect of the NDVI on the above association across age, gender, and residence, the findings presented that females, the elderly, and respondents living in urban areas were at a greater risk of having dyslipidemia, although the protective effect of the NDVI was considered. Likewise, the moderate effect of the NDVI gradually decreased as the level of depression increased in different groups. The current study conducted in China provides insights into the association between mental health, green space, and dyslipidemia. Hence, improving mental health and green spaces can be potential targets for medical interventions to decrease the prevalence of dyslipidemia.
Subject(s)
Dyslipidemias , Residence Characteristics , Middle Aged , Aged , Adult , Female , Humans , Longitudinal Studies , China/epidemiology , Parks, Recreational , Dyslipidemias/epidemiologyABSTRACT
INTRODUCTION: Understanding the social determinants that influence adolescent smoking behavior has a meaningful impact on adolescent health. Few studies have simultaneously analyzed the impact of teacher smoking and peer smoking on adolescent smoking. Therefore, the present study aims to investigate the impact of teacher smoking, peer smoking, and other social factors, on adolescent smoking. METHODS: The participants were drawn from schools in Beijing, China, in 2011, 2013, and 2015, using a multi-stage random group sampling method. The number of schools selected for each year was 160. The study participants were 57240 adolescents aged 8-19 years. The generalized linear model with a binomial distribution and logarithmic link function was used to estimate the influence of social determinants on adolescent smoking behavior. RESULTS: The results show that both teacher smoking and peer smoking were significantly associated with adolescent smoking. Compared to adolescents whose teachers did not smoke, the prevalence ratio (PR) was 1.28 for adolescents with one teacher who smoked and 1.34 for adolescents with two or more teachers who smoked (95% CI: 1.16-1.41/1.23-1.46, p<0.001/0.001, respectively). Compared to adolescents whose peers did not smoke, the prevalence ratio (PR) was 3.73 for adolescents with one peer who smoked and 8.52 for adolescents with two or more peers who smoked (95% CI: 3.20-4.35/7.48-9.69, p<0.001/0.001, respectively). CONCLUSIONS: Teacher smoking and peer smoking are significant social determinants of adolescent smoking. Prevention programs should concurrently target peer groups, school settings, and individual students.
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The phase equilibria of the Ag-Ni-Zr ternary system were investigated based on the key experiments coupled with thermodynamic modeling. Thirty ternary alloys were prepared to determine the isothermal sections of the Ag-Ni-Zr system at 500, 700 and 900 °C, respectively, by means of X-ray diffraction (XRD) and scanning electron microscopy equipped with energy dispersive X-ray spectroscopy (SEM/EDS). Based on the thermodynamic descriptions of three binary systems available in the literature as well as the experimental phase equilibrium data obtained from the present work, ten three-phase regions were determined. No ternary compound was found. The maximum solubilities of Ag in the Ni-Zr binary compounds and Ni in the Ag-Zr binary compounds were measured. The substitutional model and sublattice model were used to describe the solution phases and intermediate phases, respectively. Based on the thermodynamic descriptions of three constituent binary systems as well as the experimental phase equilibrium data obtained from the present work, a thermodynamic assessment of the Ag-Ni-Zr system was carried out using the CALPHAD (CALculation of PHAse Diagrams) approach. A set of thermodynamic parameters were obtained and the isothermal sections of the Ag-Ni-Zr system were calculated. The calculated results agree well with the experimental data.
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Background: Studies have not provided clear enough evidence on the direct association between cigarette smoking and poverty. This study aims to assess the association of householder smoking with near-poverty households, and the potential mediating effect of NCDs. Methods: A cross-sectional survey was conducted from November 2019 to October 2020 in relatively underdeveloped regions in China. In total, 2,409 households were investigated in areas under the jurisdiction of 24 primary health care (PHC) institutions of eight provinces. Pearson's χ2-test was performed, and multivariable logistic regression and extended probit regression models were fitted to examine the association between householder smoking and near-poverty households. Moreover, generalized structural equation modeling was used to explore the mediating effect of NCDs. Results: After adjusting for all other potential confounding factors, compared with households headed by never-smokers, households headed by smokers exhibited significantly elevated risks of being near poverty, with an odds ratio of 2.01 (95% CI: 0.48-0.91). We also found that living in rural areas and having a low education level both had a negative effect on being near poverty. Additionally, NCDs had a significantly positive mediating effect, with a 31.57% effect of householder smoking on near-poverty status mediated by NCDs; the indirect effect was estimated to be 0.17 (95% CI: 0.04-0.31). Conclusions: Householder smoking significantly elevated the risk of the household being near poverty, and suffering NCDs had a positive mediating effect.
Subject(s)
Family Characteristics , Poverty , China/epidemiology , Cross-Sectional Studies , Smoking/epidemiologyABSTRACT
Objective: The purpose of this study was to investigate the association between smoking and health-related quality of life among Chinese individuals aged 40 years and older. Method: Using a stratified multistage sampling method, data from 1,543 adults aged 40 years and older were obtained from a household survey conducted in eight provinces in China. The health-related quality of life was quantified based on the utility index obtained using a standardized instrument entitled "The European Five-Dimensional Health Scale (EQ-5D-5L)." Descriptive statistics were used to summarize the demographic characteristics and social factors of the sample according to smoking status. An instrumental variable (IV) probit model was used to estimate the association between smoking status and health-related quality of life. Results: Of the 1,543 participants, 485 (31.43%) were smokers and 1,058 (68.57%) were non-smokers. Smoking was negatively associated with the probability of having a higher quality of life (p < 0.01). For smokers, the average probability of having a higher quality of life was 11.65% lower than when they did not smoke. Conclusions: These findings suggest that smoking reduces health-related quality of life among Chinese individuals aged 40 years and older. Anti-smoking programs should consider this factor.
Subject(s)
Asian People , Quality of Life , Adult , China/epidemiology , Cross-Sectional Studies , Humans , Middle AgedABSTRACT
A steady-state, high-flux N2/Ar helicon wave plasma (HWP) with a small diameter (10 mm) was used to nitride the interior of a slender austenitic stainless steel (ASS) 316L tube at a temperature of 450 °C. N2 and Ar were fed to a 500 mm long slender tube with 10 mm inner diameter and were ionized inside the tube using a helicon wave in the magnetic field of 2000 G. The microstructure and depth of the nitrided layers, in addition to the morphology and hardness of the nitrided surfaces, were intensively characterized by employing scanning electron microscopy (SEM), optical microscopy (OM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), as well as microhardness tests. The results confirmed that the nitrided layer consisted primarily of the expanded austenite phase γN, and neither CrN nor iron nitride precipitates. An increasing trend in microhardness was observed in inductively coupled plasma (ICP) and HWP modes; however, the increase in HWP nitriding (up to HV 1820 with a thickness of 14 µm) was approximately 1.5 times greater than that achieved through ICP plasma nitriding. This was owing to the higher N+ ion density in the HWP mode. Considering the successful control of N2 plasma discharge in a slender tube with a small diameter, this study opens up a new avenue for achieving high-yield nitride layers inside slender tubes.
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The mechanism of acceleration, loss, and wave-particle interaction of energetic particles in the magnetosphere is a research content of the Space Plasma Environment Research Facility, which is being built as a user facility at the Harbin Institute of Technology in China. Two magnetic perturbation coils are used to simulate the magnetic storm distortion and excite Alfvén wave perturbation. A capacitor-based pulsed power supply (PPS) system with a modular design is developed to excite the magnetic perturbation coils to generate the required amplitude and duration of the magnetic field. The two magnetic perturbation coils are the CRDI coil and CRDII coil and are excited by one set of PPSs. The PPS for the CRDI coil consists of two modules and can provide a pulsed current of no less than 132 kA at 0.12 ms when the charging voltage is 20 kV, and the duration of the pulsed current from the peak to 10% of the peak is no more than 0.7 ms. The PPS for the CRDII coil consists of five modules and can provide a pulsed current of no less than 16 kA at 0.45, 0.65, 0.8, 0.95, and 1.1 ms, and the duration of the pulsed current from the peak to 10% of the peak is no more than 4.5 ms. The detailed design of the PPSs has been discussed in this paper, and the discharge test of the PPSs is carried out to verify the design of the PPSs.
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A magnet system is used in the SPERF to create the magnetic field configuration for simulating the space plasma environment. In this paper, the parameters of the system are designed to achieve the target fields needed by the scaling laws, and the electromagnetic analysis has been performed to validate the results. A procedure to obtain the parameters is proposed based on the investigation into the physical and technological constraints. The vacuum magnetic fields for studying the 3D magnetic reconnection at the magnetopause, Earth's magnetosphere, and 3D magnetic reconnection driven by a plasma gun are computed. In addition, the engineering complexity is reviewed in brief. This research is crucial to the construction of the SPERF, and it is valuable to designing the magnets applied in other fields.
ABSTRACT
The Space Plasma Environment Research Facility currently under construction at the Harbin Institute of Technology in China uses four magnetosheath coils (flux cores) and a dipole coil to generate the magnetic field required for the study on the magnetopause magnetic reconnection. Two groups of magnetopause shape control coils (labeled CK coils) are used to slightly adjust the magnetic field distribution on the magnetopause. A capacitive pulsed power supply (PPS) system with a modular design is developed to excite CK coils. The PPS system consists of six sets of PPS with the same principle and structure, which are used to excite six sub-coils of the CK coils, respectively. Each set of PPS consists of ten modules and one local controller, and each module consists of a charger and discharge unit. Each set of PPS can provide a pulsed current of no less than 400 kA for the corresponding sub-coil at 0.11 ms when the charging voltage is 20 kV, and the duration of the pulsed current from the peak to 10% of the peak is no more than 0.6 ms. The detailed design of the PPS is discussed in this paper, and the discharge test of the PPS is carried out to verify the design of the PPS. Because there are acquisition and control devices in the discharge unit, the electromagnetic interference immunity design is also discussed to ensure the normal operation of the PPS.
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The robustness of carbon nanomaterials and their potential for ultrahigh permeability has drawn substantial interest for separation processes. However, graphene oxide membranes (GOms) have demonstrated limited viability due to instabilities in their microstructure that lead to failure under cross-flow conditions and applied hydraulic pressure. Here we present a highly stable and ultrapermeable zeolitic imidazolate framework-8 (ZIF-8)-nanocrystal-hybridized GOm that is prepared by ice templating and subsequent in situ crystallization of ZIF-8 at the nanosheet edges. The selective growth of ZIF-8 in the microporous defects enlarges the interlayer spacings while also imparting mechanical integrity to the laminate framework, thus producing a stable microstructure capable of maintaining a water permeability of 60 l m-2 h-1 bar-1 (30-fold higher than GOm) for 180 h. Furthermore, the mitigation of microporous defects via ZIF-8 growth increased the permselectivity of methyl blue molecules sixfold. Low-field nuclear magnetic resonance was employed to characterize the porous structure of our membranes and confirm the tailored growth of ZIF-8. Our technique for tuning the membrane microstructure opens opportunities for developing next-generation nanofiltration membranes.
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BACKGROUND: Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a significant cause of morbidity among haemodialysis patients and is associated with pathological changes in phosphate, calcium and parathyroid hormone (PTH). In the ACTIVE Dialysis study, extended hours dialysis reduced serum phosphate but did not cause important changes in PTH or serum calcium. This secondary analysis aimed to determine if changes in associated therapies may have influenced these findings and to identify differences between patient subgroups. METHODS: The ACTIVE Dialysis study randomised 200 participants to extended hours haemodialysis (≥24 h/week) or conventional haemodialysis (≤18 h/week) for 12 months. Mean differences between treatment arms in serum phosphate, calcium and PTH; and among key subgroups (high vs. low baseline phosphate/PTH, region, time on dialysis, dialysis setting and frequency) were examined using mixed linear regression. RESULTS: Phosphate binder use was reduced with extended hours (- 0.83 tablets per day [95% CI -1.61, - 0.04; p = 0.04]), but no differences in type of phosphate binder, use of vitamin D, dose of cinacalcet or dialysate calcium were observed. In adjusted analysis, extended hours were associated with lower phosphate (- 0.219 mmol/L [- 0.314, - 0.124; P < 0.001]), higher calcium (0.046 mmol/L [0.007, 0.086; P = 0.021]) and no change in PTH (0.025 pmol/L [- 0.107, 0.157; P = 0.713]). The reduction in phosphate with extended hours was greater in those with higher baseline PTH and dialysing at home. CONCLUSION: Extended hours haemodialysis independently reduced serum phosphate levels with minimal change in serum calcium and PTH levels. With a few exceptions, these results were consistent across patient subgroups. TRIAL REGISTRATION: Clinicaltrials.gov NCT00649298 . Registered 1 April 2008.
Subject(s)
Chronic Kidney Disease-Mineral and Bone Disorder/blood , Chronic Kidney Disease-Mineral and Bone Disorder/epidemiology , Renal Dialysis/methods , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/therapy , Adult , Biomarkers/blood , Female , Humans , Male , Middle Aged , Time FactorsABSTRACT
BACKGROUND: Problems of irrational antibiotic use by prescribers are ongoing and have escalated following reductions in the cost of essential drugs policy. In an attempt to improve prescribing practices for village doctors and rational use of essential drugs, a program designed to audit and monitor drug use was established. However, the effects of the program to control antibiotic resistance and changing the village doctors' prescribing behaviors remain largely unknown. This study measured the effect of the program on levels of antibiotic use. METHOD: Data was collected covering a 22-month period, before, during and after the program was implemented in rural clinics. Segmented regression analysis with interrupted time series (ITS) data was used to examine whether there had been a significant interaction with the onset of the program in September 2011 and levels of antibiotic use from November 2010 to August 2012. Both serial and 12-month lag autocorrelations were controlled for. RESULTS: A noticeable drop about 6.15% per month (95% CI: -13.36%; 1.06%, P = 0.089) for the antibiotic use in outpatients, which is lower of effect size assuming that the program has the immediate impact of the program were captured for the immediate effect of the program. Meanwhile, levels of antibiotic use would have continued to decrease by 1.12% per month (P = 0.034) as they did in the absence of the program. CONCLUSION: The central finding was that the prescription audit and feedback program was associated with significant decreases (P = 0.034) in antibiotic use after its implementation.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Utilization Review , Prescription Drug Overuse/prevention & control , Drug Prescriptions/statistics & numerical data , Feedback , Humans , Interrupted Time Series Analysis , Medical Audit , Practice Patterns, Physicians' , Prescription Drug Overuse/statistics & numerical data , Regression Analysis , Rural Health Services/statistics & numerical dataABSTRACT
INTRODUCTION AND AIM: Accurately predicting the prognosis of individual patient is crucial in the management of ACLF. We aimed to establish a specific prognostic model for HBV-related ACLF patients treated with nucleoside analog (NA). MATERIAL AND METHODS: We prospectively collected 205 ACLF cases diagnosed according to the APASL criteria. A dynamic prognostic model based on APASL criteria was established and validated. To demonstrate that the model is also applicable to those within EASL criteria, we divided the patients into two groups: met APASL criteria only (group A, n = 123); met both APASL and EASL criteria (group B, n = 82). Its prognostic accuracy was also compared with chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in group B. RESULTS: The model is: R = 0.94 x Bilirubin + 0.53 x evolution of Bilirubin - 0.45 x PT-A - 0.22 x evolution in PT-A -0.1 x PLT + 10 x anti-HBe. The area under receiver operating characteristic curve (AUC) of the model for predicting 90-day mortality was 0.86, which was significantly higher than that of model for end stage liver disease(MELD), MELD-Na, CLIF-SOFA, ΔMELD (7d) and ΔMELD-Na (7d), ΔCLIF- SOFA(7d) (all p < 0.01). The AUC of our model in the validation group was 0.79 which was superior to MELD (0.45) CLIF-SOFA (0.53) score in group B patients (p < 0.01). CONCLUSION: In conclusion, the model was superior to the conventional methods in predicting the outcomes of patients with HBV related ACLF treated with NA. It is the first description of a novel prognostic model using consecutive data in patients with HBV-induced acute-on-chronic liver failure (ACLF) treated by nucleoside analogs.
Subject(s)
Acute-On-Chronic Liver Failure/drug therapy , Antiviral Agents/therapeutic use , Decision Support Techniques , Hepatitis B virus/drug effects , Hepatitis B, Chronic/drug therapy , Models, Biological , Nucleosides/therapeutic use , Acute-On-Chronic Liver Failure/diagnosis , Acute-On-Chronic Liver Failure/mortality , Acute-On-Chronic Liver Failure/virology , Adult , Antiviral Agents/adverse effects , Bilirubin/blood , Biomarkers/blood , China , Disease Progression , Female , Hepatitis B Antibodies/blood , Hepatitis B e Antigens/immunology , Hepatitis B virus/immunology , Hepatitis B virus/pathogenicity , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/mortality , Hepatitis B, Chronic/virology , Humans , Male , Middle Aged , Nucleosides/adverse effects , Organ Dysfunction Scores , Predictive Value of Tests , Prospective Studies , Prothrombin/metabolism , Reproducibility of Results , Time Factors , Treatment OutcomeABSTRACT
AIM: It is challenging to predict the outcome of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) through existing prognostic models. Our aim was to establish a novel dynamic model to improve the predictive efficiency of 30-day mortality in HBV-ACLF patients. METHODS: 305 patients who were diagnosed as HBV-ACLF (derivation cohort, n=211; validation cohort, n=94) were included in this study. The HBV-ACLF dynamic (HBV-ACLFD) model was constructed based on the daily levels of predictive variables in 7 days after diagnosis combined with baseline risk factors by multivariate logistic regression analysis. The HBV-ACLFD model was compared with the Child-Turcotte-Pugh (CTP) score, end-stage liver disease (MELD) score, and MELD within corporation of serum sodium (MELD-Na) score by the area under the receiver-operating characteristic curves (AUROC). RESULTS: The HBV-ACLFD model demonstrated excellent discrimination with AUROC of 0.848 in the derivation cohort and of 0.813 in the validation cohort (p=0.620). The performance of the HBV-ACLFD model appeared to be superior to MELD score, MELD-Na score and CTP score (P<0.0001). CONCLUSION: The HBV-ACLFD model can accurately predict 30-day mortality in patients with HBV-ACLF, which is helpful to select appropriate clinical procedures, so as to relieve the social and economic burden.
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Human Vγ2Vδ2 T cells monitor isoprenoid metabolism by recognizing foreign (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), a metabolite in the 2-C-methyl-D-erythritol-4-phosphate pathway used by most eubacteria and apicomplexan parasites, and self isopentenyl pyrophosphate, a metabolite in the mevalonate pathway used by humans. Whereas microbial infections elicit prolonged expansion of memory Vγ2Vδ2 T cells, immunization with prenyl pyrophosphates or aminobisphosphonates elicit short-term Vγ2Vδ2 expansion with rapid anergy and deletion upon subsequent immunizations. We hypothesized that a live, attenuated bacterial vaccine that overproduces HMBPP would elicit long-lasting Vγ2Vδ2 T cell immunity by mimicking a natural infection. Therefore, we metabolically engineered the avirulent aroA(-) Salmonella enterica serovar Typhimurium SL7207 strain by deleting the gene for LytB (the downstream enzyme from HMBPP) and functionally complementing for this loss with genes encoding mevalonate pathway enzymes. LytB(-) Salmonella SL7207 had high HMBPP levels, infected human cells as efficiently as did the wild-type bacteria, and stimulated large ex vivo expansions of Vγ2Vδ2 T cells from human donors. Importantly, vaccination of a rhesus monkey with live lytB(-) Salmonella SL7207 stimulated a prolonged expansion of Vγ2Vδ2 T cells without significant side effects or anergy induction. These studies provide proof-of-principle that metabolic engineering can be used to derive live bacterial vaccines that boost Vγ2Vδ2 T cell immunity. Similar engineering of metabolic pathways to produce lipid Ags or B vitamin metabolite Ags could be used to derive live bacterial vaccine for other unconventional T cells that recognize nonpeptide Ags.
Subject(s)
Metabolic Engineering/methods , Receptors, Antigen, T-Cell, gamma-delta/immunology , Salmonella Vaccines/immunology , Salmonella typhimurium/immunology , T-Lymphocytes/immunology , Animals , Bacterial Proteins/genetics , Bacterial Proteins/immunology , Bacterial Proteins/metabolism , Cell Proliferation , Cells, Cultured , Gene Deletion , Humans , Immunization , Lymphocyte Activation/immunology , Macaca mulatta/immunology , Metabolic Networks and Pathways/genetics , Metabolic Networks and Pathways/immunology , Mevalonic Acid/metabolism , Organophosphates/metabolism , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Salmonella typhimurium/genetics , Salmonella typhimurium/metabolism , T-Lymphocytes/metabolismABSTRACT
BACKGROUND: It is unclear whether changing the governance structure of community health centres (CHCs) could affect antibiotic prescribing behaviour. OBJECTIVE: To explore how changes in governance structure affect antibiotic prescription for children younger than 5 years of age with acute upper respiratory tract infections (AURI) in CHCs in Shenzhen, China. METHODS: This study used an interrupted time series design with a comparison series. On 1 June 2009, the Health Bureau of Shenzhen's Baoan District transferred CHCs from a hospital-affiliated model to a self-managed independent model regarding finance, personnel and employee compensation. We collected 23481 electronic medical records of children younger than 5 years of age who were treated for AURI on an outpatient basis 1 year before and 1 year after governance structure reform. We used segmented regression analysis to evaluate the effect of reform on antibiotic prescription. RESULTS: After the reform, the proportion of patients receiving an antibiotic injection per month and the proportion of patients receiving two or more antibiotics conditional on receiving an antibiotic per month decreased 9.17% and 7.34%, respectively (P < 0.01 or P < 0.05). In the intervention series, the proportion of patients receiving an antibiotic injection per month and the monthly average cost of the antibiotics prescribed per patient continued to decrease over time compared with the control series (P < 0.001 or P < 0.05). CONCLUSION: This study suggests that governance structure reform can have positive effects on behaviour for antibiotic prescribing. Moreover, this short-term effect might have important implications for further community health reforms in China.