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Abstract Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). We found that overexpression of CPT1A in the RPE of Vldlr −/− mice suppresses epithelial-to-mesenchymal transition and fibrosis. Mechanistically, TGFβ2 induces fibrosis by activating a Warburg-like effect, i.e. increased glycolysis and decreased mitochondrial respiration through ERK-dependent CPT1A degradation. Moreover, VLDLR blocks the formation of the TGFβ receptor I/II complex by interacting with unglycosylated TGFβ receptor II. In conclusion, VLDLR suppresses fibrosis by attenuating TGFβ2-induced metabolic reprogramming, and CPT1A is a potential target for treating subretinal fibrosis.

Background Cardiovascular disease has declined but remains a major disease burden across developed countries. Objective To assess the effectiveness and cost-effectiveness of statin therapy across United Kingdom population categories. Design The cardiovascular disease microsimulation model, developed using Cholesterol Treatment Trialists’ Collaboration data and the United Kingdom Biobank cohort, projected cardiovascular events, mortality, quality of life and healthcare costs using participant characteristics. Setting United Kingdom primary health care. Participants A total of 117,896 participants in 16 statin trials in the Cholesterol Treatment Trialists’ Collaboration; 501,854 United Kingdom Biobank participants by previous cardiovascular disease status, sex, age (40–49, 50–59 and 60–70 years), 10-year cardiovascular disease risk [QRISK®3 (%):

Abstract Background Adherence to antiparkinsonian drugs (APDs) is critical for patients with Parkinson’s disease (PD), for which medication is the main therapeutic strategy. Previous studies have focused on specific disorders in a single system when assessing clinical factors affecting adherence to PD treatment, and no international comparative data are available on the medical costs for Chinese patients with PD. The present study aimed to evaluate medication adherence and its associated factors among Chinese patients with PD using a systematic approach and to explore the impact of adequate medication adherence on direct medical costs. Methods A retrospective analysis was conducted using the electronic medical records of patients with PD from a medical center in China. Patients with a minimum of two APD prescriptions from January 1, 2016 to August 15, 2018 were included. Medication possession ratio (MPR) and proportion of days covered were used to measure APD adherence. Multiple linear regression analysis was used to identify factors affecting APD adherence. Gamma regression analysis was used to explore the impact of APD adherence on direct medical costs. Results In total, 1,712 patients were included in the study, and the mean MPR was 0.68 (± 0.25). Increased number of APDs and all medications, and higher daily levodopa-equivalent doses resulted in higher MPR (mean difference [MD] = 0.04 [0.03–0.05]; MD = 0.02 [0.01–0.03]; MD = 0.03 [0.01–0.04], respectively); combined digestive system diseases, epilepsy, or older age resulted in lower MPR (MD = -0.06 [-0.09 to -0.03]; MD = -0.07 [-0.14 to -0.01]; MD = -0.02 [-0.03 to -0.01], respectively). Higher APD adherence resulted in higher direct medical costs, including APD and other outpatient costs. For a 0.3 increase in MPR, the two costs increased by $34.42 ($25.43–$43.41) and $14.63 ($4.86–$24.39) per year, respectively. Conclusions APD adherence rate among Chinese patients with PD was moderate and related primarily to age, comorbidities, and healthcare costs. The factors should be considered when prescribing APDs.

Summary: Background: Cardiovascular disease incidence and mortality have declined across developed economies and granular up-to-date cost-effectiveness evidence is required for treatments targeting large populations. To assess the health benefits and cost-effectiveness of standard and higher intensity statin therapy in the contemporary UK population 40–70 years old. Methods: A cardiovascular disease microsimulation model, developed using the Cholesterol Treatment Trialists' Collaboration data (117,896 participants; 5 years follow-up), and calibrated in the UK Biobank cohort (501,854 participants; 9 years follow-up), projected risks of myocardial infarction, stroke, coronary revascularization, diabetes, cancer and vascular and nonvascular death for all UK Biobank participants without and with statin treatment. Meta-analyses of trials and cohort studies informed statins’ relative effects on cardiovascular events, incident diabetes, myopathy and rhabdomyolysis. UK healthcare perspective was taken (2020/2021 UK£) with costs per 28 tablets of £1.10 for standard (35%–45% LDL cholesterol (LDL-C) reduction) and £1.68 for higher intensity (≥45% LDL-C reduction) generic statin. Findings: Across categories by sex, age, LDL-C, and cardiovascular disease history/10-year cardiovascular risk, lifetime standard statin increased survival by 0.28–1.85 years (0.20–1.09 quality-adjusted life years (QALYs)), and higher intensity statin by further 0.06–0.40 years (0.03–0.20 QALYs) per person. Standard statin was cost-effective across all categories with incremental cost per QALY from £280 to £8530, with higher intensity statin cost-effective at higher cardiovascular risks and higher LDL-C levels. Stopping statin early reduced benefits and was not cost-effective. Interpretation: Lifetime low-cost statin therapy is cost-effective across all 40–70 years old in UK. Strengthening and widening statin treatment could cost-effectively improve population health. Funding: UK NIHR Health Technology Assessment Programme (17/140/02).

To solve the problem of environmental pollution, Distiller's dried grains (DDGS), a biomass, is used as a clean reducing agent for the leaching process of pyrolusite. Experimental results have shown that the leaching rate of manganese can reach 92.1% with the optimized conditions including a sulfuric acid concentration of 3.5 mol/L, a DDGS to pyrolusite ratio of 0.4, a liquid–solid ratio of 3 mL/g, a temperature of 363K, a time of 3 h, and a rotation speed of 400 rpm. This article explored the mechanism of the entire leaching process: the crude fiber in DDGS is hydrolyzed into reducing sugars, and the MnO2 in pyrolusite undergoes an oxidation–reduction reaction to generate Mn2+ and studied the kinetics of the leaching process following the unreacted shrinkage nuclear reaction model controlled by the surface chemical reaction (1-(1-X)1/3 = kt). The equation of leaching kinetics is 1−1−X13=3738.06·[H2SO4]0.57·[LS]0.78·[DDGSpyrolusite]0.25·[rpm]0.09·exp(−48.448/(RT)) This work provides a green and effective leaching process for the leaching of pyrolusite.

Abstract The augmented Young–Laplace (AYL) equation has been widely used to describe the liquid–vapor interfaces affected by capillarity and adsorption, particularly in nanoporous or clay minerals where strong adsorptive interaction prevails. Still, how adsorption ultimately shapes the liquid–vapor interface in pores remains elusive. All current forms of the AYL equation only consider the attractive van der Waals interaction for complete wetting surface and are mostly an extension of the general equation based on thermodynamic principles without rigorous derivation. In this paper, closed forms of the AYL equations are derived by variational calculus method for two typical pore models considering effects of capillarity and adsorption, based on the minimization of free energy for the equilibrium system. The van der Waals, electrical, and structural forces are incorporated as disjoining pressure into the proposed AYL equations to quantify effects of both attractive and repulsive interactions (hence complete and partial wetting conditions) on interfacial geometry and equilibrium matric potential. Numerical calculation algorithms are established to solve the interfacial geometric profiles and characteristics. The proposed model illustrates a transition region on the interface where geometry and physical characteristics are drastically altered under adsorption compared with sole capillarity. Different surface wettabilities are examined for interface profiles and curvature distributions. An apparent contact angle on the partial wetting surface is identified that is approaching complete wetting as the adsorption dominates when pore size reduces. Water retention and interparticle force demonstrate clear distinctions in their evolution, with different particle sizes and varying half‐filling angles under adsorptive conditions as water volume changes.

The occurrence of future unrelated medical costs is a direct consequence of life-prolonging interventions, but most pharmacoeconomic guidelines recommend the exclusion of these costs. The Chinese guidelines were updated in 2020, taking an exclusion approach for the future unrelated medical cost. We notice the research surrounding this issue continues in other countries and leads to an inclusion recommendation in some guidelines. Meanwhile, this issue has not been discussed in China, reflecting an urgent need for extensive research on its impact. We reviewed the theoretical and practical studies surrounding the inclusion of future unrelated medical costs, summarised the landscape of guidelines in other jurisdictions. We found that the inclusion would increase the internal and external consistency of economic evaluation and the comparability of results between different jurisdictions. However, more research is needed surrounding this issue. We proposed a future research agenda to inform the update of Chinese guidelines. We recommend research on individual-level healthcare reimbursement data and end-of-life costs from hospital administrative data to generate the age-specific, sex-specific and condition-specific costs. We also recommend establishing a formal process to evaluate the ethical and economic impact of including future unrelated medical costs and adjust the threshold accordingly in the guidelines.

Abstract Background Although significant improvement in efficacy measured by a sustained virological response, the high acquisition costs of direct-acting antivirals limit the access for patients and influence the costs of healthcare resource utilisation in hepatitis C. It is important to have the latest estimates of prevalence, especially in high-risk groups, for cost of illness, cost-effectiveness and budget impact studies. Methods Original studies on the estimates of the prevalence among general and high-risk groups in the European Union/European Economic Area (EU/EEA) were retrieved from Medline and Embase for the period from 2015 to 2018. All included studies were evaluated for risk of selection bias and summarised together in a narrative form. Results from previous reviews and updated searches were compared per country among different populations, respectively. Results Among the 3871 studies identified, 46 studies were included: 20 studies were used for the estimate of the general population; 3 for men who have sex with men (MSM); 6 for prisoners; and 17 for people who inject drugs (PWID). Compared with the results reported in previous systematic reviews, the updated estimates were lower than previously in most available countries. Anti-HCV general population prevalence estimates ranged from 0.54 to 1.50% by country. The highest prevalence of anti-HCV was found among PWID (range of 7.90–82.00%), followed by prisoners (7.00–41.00%), HIV-positive MSM (1.80–7.10%), HIV-negative MSM (0.20–1.80%), pregnant women (0.10–1.32%) and first-time blood donors (0.03–0.09%). Conclusions Our study highlights the heterogeneity in anti-HCV prevalence across different population groups in EU/EEA. The prevalence also varies widely between European countries. There are many countries that are not represented in our results, highlighting the need for the development of robust epidemiological studies.

Personal protective air filtration masks are becoming increasingly desirable, but most commercial air purifiers have poor biocidal capabilities. Here the authors fabricate metal–organic framework-based air filters with both high particulate matter removal efficiencies and photocatalytic bactericidal properties.

Bactrian camels (Camelus bactrianus) are highly adapted to the desert and semi-desert environments of Asia and developed unique physiological adaptations to cold, heat, drought, and nutrient-poor conditions. These animals are an ideal model for studying desert adaptation. However, the transcriptome of different Bactrian camel tissues has not been profiled. This study performed a comprehensive transcriptome analysis of nine fetal and adult tissues. A total of 20,417 coding genes were identified, and 2.4 billion reads were generated. Gene expression and functional analyses revealed that approximately 50% of the identified genes were ubiquitously expressed, and one-third were tissue-elevated genes, which were enriched in pathways related to the biological functions of the corresponding tissue. Weighted gene co-expressed network analysis (WGCNA) identified four modules—fat metabolism, water balance, immunity, and digestion—and several hub genes, including APOA1, TMEM174, CXCL12, and MYL9. The analysis of differentially expressed genes (DEGs) between fetal and adult tissues revealed that downregulated genes were enriched in tissue development, whereas upregulated genes were enriched in biological function in adult camels. DEGs in the hump were enriched in immune-related pathways, suggesting that this tissue is involved in immunity. This study is the first to generate a transcriptome atlas of major tissues in Bactrian camels and explores the genes potentially involved in the adaptation to desert environments.

We investigate the antimicrobial activity of combined colistin and gamithromycin against nine Pasteurella multocida strains by testing in vitro susceptibility. Two high-colistin minimal inhibitory concentration (MIC) isolates (D18 and T5) and one low-colistin MIC isolate (WJ11) were used in time-kill tests and therapeutic effect experiments using a neutropenic murine pneumonia model over 24 h. Pharmacokinetics (PK) in plasma was calculated along with pharmacodynamics (PD) to determine the PK/PD index. Synergy between colistin and gamithromycin was observed using high-colistin MIC isolates, equating to a 128- or 256-fold and 4- or 8-fold reduction in colistin and gamithromycin concentration, respectively. Interestingly, no synergistic effect of the combination on low-colistin MIC isolates was observed. However, regardless of the MIC difference among isolates, each drug tended to reach the same concentration in all isolates subjected to combined treatments, which was verified by the time-kill tests presenting similar rates and extent of killing for isolates D18, T5, and WJ11. The AUC(0–24 h)/MIC index was used to evaluate the relationship between PK and PD, and the correlation was >0.89. The relevant gamithromycin doses for combined therapy were determined, and the value decreased from 6- to 35-fold compared with monotherapy. Combined colistin and gamithromycin therapy provides a more potent therapeutic regimen than monotherapy against P. multocida strains.

Background and Objectives: Utility elicitation studies for schizophrenia generate different utility values for the same health states. We reviewed utility values used in schizophrenia pharmacoeconomic evaluations and evaluated the impact of their selection on the incremental cost-effectiveness ratio (ICER). Methods: A systematic search was performed in Medline and Embase. Health state definitions, associated utility values, elicitation studies, and value selection processes were extracted. Sets of utility values for all schizophrenia health states were used in a cost-effectiveness model to evaluate the ICER. Results: Thirty-five cost-utility analyses (CUAs) referring to 11 utility elicitation studies were included. The most frequent health states were ‘stable’ (28 CUAs, 7 utility elicitation studies, 10 values, value range 0.650–0.919), ‘relapse requiring hospitalisation’ (18, 5, 7, 0.270–0.604), ‘relapse not requiring hospitalisation’ (18, 5, 10, 0.460–0.762), and ‘relapse only’ (10, 5, 6, 0.498–0.700). Seventeen sets of utility values were identified with difference in utility values between relapse and stable ranging from −0.358 to −0.050, resulting in ICERs ranging from −56.2% to +222.6% from average. Conclusion: The use of utility values for schizophrenia health states differs among CUAs and impacts on the ICER. More rigorous and transparent use of utility values and sensitivity analysis with different sets of utility values are suggested for future CUAs.

Objectives: We aimed to conduct a modelling study to estimate and predict the economic burden of AD to support the healthcare management of AD in China. Methods: The economic burden of AD was estimated with an evaluation of the prevalence of AD patients and a simulation of annual resource use and cost per AD patient in China using a published model. Percentage of AD patients being treated was assumed to be 5% from 2010 to 2050, with three scenarios testing the value of this parameter of 10%, 20% and 40% throughout 2020 to 2050. Results: The costs of AD were estimated to be from around 91 billion RMB in 2010 to 332 billion in 2050. Most of the current burden was related to private caregivers paid by families. With the percentage of patients being treated changing from 5% to 40%, costs were estimated to double. This was related to more hospitalisations and more use of care facilities, while the burden for families would decrease. Conclusion: A high economic burden related to AD is predicted. The burden would be driven mainly by indirect costs related to the social support of the patients. Investment in improving awareness and care of AD patients is needed and worth it.

Shipping heavy-duty goods or equipment is being a new sector recently, and the pallet is rather important. In this article, a comparison of various materials revealed that laminated veneer lumber was ideal for heavy-duty packaging industry. For various pallets with random parameters, a hybrid reliability optimization design method was proposed, which aimed to provide an effective computational tool for reliability design of pallet system. With first-order second-moment method, the separation and combination of component and system failure probabilities were obtained. Several case studies were included to illustrate the computational procedures, as well as to discuss the effects of dimension and quantity of members. Using design of experiment method, the sensitivities of each parameter were significant, and the optimization of whole system was realized. To reduce the cost, recycling and standardization were worth considering in the future.

Background: Economic models are broadly used in the economic evaluation of antipsychotics in schizophrenia. Our objective was to summarize the structure of these models. Methods: Model-based economic evaluations of antipsychotics in schizophrenia were identified through Medline and Embase. General information was extracted including analysis type, model type, perspective, population, comparator, outcome, and timeframe. Model-specific structures for decision tree (DT), cohort- and patient-level Markov model (CLMM, PLMM), and discrete-event simulation (DES) models were extracted. Results: A screen of 1870 records identified 79 studies. These were mostly cost-utility analyses (n = 48) with CLMM (n = 32) or DT models (n = 29). They mostly applied payer perspective (n = 68), focused on general schizophrenia for relapse prevention (n = 73), compared pharmacotherapies as first-line (n = 71), and evaluated incremental cost per quality-adjusted life year (QALY) gained (n = 40) with a 1-year (n = 32) or 5-year (n = 26) projection. DT models progressed with the branching points of response, relapse, discontinuation, and adherence. CLMM models transitioned between disease states, whereas PLMM models transitioned between adverse event states with/without disease state. DES models moved forward with times to remission, relapse, psychiatrist visit, and death. Conclusions: A pattern of pharmacoeconomic models for schizophrenia was identified. More subtle structures and patient-level models are suggested for a future modelling exercise.

Parallel strand bamboo (PSB) is a latest construction material; to know more about mechanical properties of PSB, 5 groups of specimens with difference only in bolt diameter were designed to study the impact of the fastener diameter on embedding strength perpendicular to grain of PSB. Based on the tested result, the feasibility for PSB of the theoretical equation in the American code and European code on embedding strength predication was assessed. A controlled displacement was used to load till specimen failure, the stress-displacement curve of all specimens was obtained in terms of the tested results, and the yielding tested strength based on 5% bolt diameter offset proposed by the American code was found. The tested results showed that the yielding strength perpendicular to grain of PSB was stable, the variable coefficient was between 5.88% and 13.34%, and the average yielding strength values were 80.84 MPa, 77.40 MPa, 76.52 MPa, 74.20 MPa, and 67.01 MPa, respectively, which decreased with the increase of bolt diameter, and the average yielding strength values are larger than the calculated results using theoretical formula. Therefore, the theoretical equation on embedding yielding strength of wood in the American code and European code applies to PSB.

Connection is an important part of the bamboo and timber structure, and it directly influences the overall structural performance and safety. Based on a comprehensive analysis of the mechanical performance of several wood connections, a new connector for the bamboo (timber) frame joint was proposed in this paper. Three full-scale T-type joint specimens were designed to study the mechanical performance under cyclic loading. The thickness of the hollow steel column was different among three specimens. The specimens were loaded under displacement control with a rate of 10 mm per minute until the specimens reach failure. It was observed that the failures of three specimens were caused by the buckling of flanges in the compression and that the steel of connections does not yield. The load-displacement hysteretic curve for three specimens is relatively plump, and the stiffness of connection degenerates with the increasing of cyclic load. The maximum rotation is 0.049 rad, and the energy dissipation coefficient is 1.77. The thickness of the hollow steel column of the connector has significant impact on the energy dissipation capacity and the strength of the connection. A simplified moment-rotation hysteresis model for the joint was proposed.

In this study, Na _2 CO _3 was used as activator to roast and activate high-alumina fly ash (HAFA), and the vacuum roasting technology was used to enhance the activation process of HAFA. The effects of the vacuum conditions on the activation of HAFA roasted using conventional and microwave heating were investigated. It was determined that the reaction time was shortened and the activation effect of HAFA was improved under vacuum conditions; however, the effect of the vacuum conditions on the roasting temperature was negligible. The activation process of HAFA-Na _2 CO _3 mixtures (HAFA/Na _2 CO _3 mass ratio of 1:1) was promoted by conducting conventional and microwave heating experiments under vacuum (−0.04 MPa). The leaching rate of aluminium of 93.00% was reached at the roasting temperature of 900 °C after only 20 min when the HAFA-Na _2 CO _3 mixture was subjected to conventional heating under vacuum, and after 60 min when conventional heating occurred under normal atmospheric pressure. Moreover, the leaching rate of aluminium of 96.00% was reached at the roasting temperature of 700 °C after only 20 min when the HAFA-Na _2 CO _3 mixture underwent microwave heating under vacuum, and after 30 min when microwave heating occurred under normal atmospheric pressure.

In this study, SiC reinforced aluminum (Al) metal matrix composites were prepared by microwave sintering. The effects of SiC content, pressure and sintering temperature on the density, hardness and microstructure of the composites were investigated. It was found that the relative density of SiC/Al composites is 98.43% when the content of SiC is 5 Vol%. When the SiC content is 15 vol%, the sintering temperature is 770 °C and the pressure is 250 MPa, the density and hardness of the composites SiC/Al composites are 96.14% and 130 HV, respectively. And the SiC particles can be uniformly dispersed in the Al matrix by microwave sintering.

We report a recent case and review some literatures of acute aortic dissection (AAD) Stanford type B complicated with late onset of acute renal failure. The patient underwent preoperational peritoneal dialysis followed by thoracic endovascular aortic repair (TEVAR) and was fully recovered and discharged soon after surgery. We conclude that an AAD case is difficult to achieve a timely diagnosis, but with attention to systemic symptoms and dedication thorough treatment plan, a full recovery and positive prognosis are expected.