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When an Autonomous Underwater Vehicle(AUV) sails near the surface of the sea,it will inevitably be subjected to wave disturbance. The heave and pitch motion caused by wave disturbance not only affects the navigation attitude of the AUV,but also leads to an increase in sailing resistance. As such, its energy consumption is increased. In this paper,the six degrees of freedom model of AUVs is established and linearized in order to achieve the weighted optimization of the sailing attitude and the resistance of the AUVs. The drag force model of the AUV is derived using the theory of potential flow. The Q matrix and R matrix are determined in the controller based on research into the drag force model. The Linear Quadratic Regulator(LQR)controller of the AUV is designed using the drag force model as the performance index. The simulation results show that after adding the LQR controller,the effects of reducing heave motion and pitch motion are 46.64% and 77.62% respectively, and the increased resistance caused by the pitch motion is reduced to 1/6 of its original value. The results show that the multiple optimum of attitude and sailing resistance is realized,the energy consumption is decreased and the endurance of the AUV is increased.

Inhaled bronchodilators are central for the treatment of chronic obstructive pulmonary disease (COPD), as they can provide symptom relief and reduce the frequency and severity of exacerbations while improving health status and exercise tolerance. In 2017, glycopyrrolate (GLY) delivered via the eFlow® closed system (CS) nebulizer (nebulized GLY; 25 µg twice daily), was approved by the US Food and Drug Administration for maintenance treatment of moderate-to-very-severe COPD. This approval was based largely on results from the replicate, placebo-controlled, Phase III clinical trials- GOLDEN 3 and 4. In this review, we summarize key findings from secondary analyses of the GOLDEN 3 and 4 studies, and provide a comprehensive overview that may assist both pulmonologists and primary-care providers in their treatment decisions. Comorbidities are common among patients with COPD in clinical practice and may impact bronchodilator efficacy. This review highlights outcomes among subpopulations of patients with comorbidities (e.g., anxiety/depression, cardiovascular disease), and their impact on the efficacy of nebulized GLY. In addition, the efficacy and safety of nebulized GLY across various demographics (e.g., age, gender) and baseline disease characteristics (e.g., disease severity, rescue medication use) are discussed. Real-world outcomes with nebulized GLY, including device satisfaction, healthcare resource utilization, and exacerbations, are also presented. These secondary analyses and real-world data complement the primary results with nebulized GLY from Phase III studies and support the need for the inclusion of patients representative of real-world clinical practice in RCTs. In addition, these data suggest that RCTs for COPD therapies should be complemented with real-world observational studies.

This study was sponsored by Novartis Pharmaceuticals Corporation, East Hanover, NJ. The funding source was involved in study design, data analysis, drafting, and approval of this abstract. Adherence to treatment remains an obstacle in achieving low-density lipoprotein cholesterol (LDL-C) targets. Inclisiran is a small-interfering RNA that targets PCSK9 messenger RNA and is approved as an adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidemia to reduce LDL-C in the US. It is administered subcutaneously by an HCP, again at 3 months and then twice yearly. Real-world studies assessing treatment patterns of inclisiran are limited. This study assessed adherence and persistence at 12 months among patients who newly initiated inclisiran, alirocumab (every 2 weeks or 1/month) or evolocumab (every 2 weeks or 1month). This retrospective, observational study utilized the US Komodo Health database from 1/1/21–8/31/23. Komodo Health is a longitudinal database that captures 330 million patients in the US from open and closed databases. Patients were ≥18 years, had 12 months of continuous enrollment before and after the index date and a first claim for inclisiran, alirocumab, or evolocumab between 1/1/22–8/31/22. Adherence was measured by the proportion of days covered (PDC): number of days covered by the drug divided by the 12-month observational period. Discontinuation was defined as a gap of >60 days for alirocumab and evolocumab, and >90 days for inclisiran between the last day of days' supply and the start of the next prescription. Days of supply (DOS) for inclisiran was assumed to be 92 days for the 1st dose and 183 days for the subsequent doses. Sensitivity analysis was performed by extending DOS by 30 and 90 days for inclisiran to reflect the flexibility in dosing schedule. A total of 852 patients were included in the inclisiran cohort; 8,878 patients in alirocumab and 27,171 in evolocumab cohort. Mean (SD) PDC at 12-month was 0.77 (0.28), 0.68 (0.33) and 0.67 (0.33) for inclisiran, alirocumab and evolocumab, respectively. The proportion of patients who discontinued the therapy was 31.6%, 44.8% and 45.3%; mean (SD) time to discontinuation was 133.52 (71.32), 119.22 (79.99), and 113.7 (80.41) days, respectively. When DOS for inclisiran was extended by 30 or 90 days, mean PDC was 0.82 (0.25) and 0.90 (0.20), respectively; discontinuation was 22.9% and 19.8% and time to discontinuation was 135.5 (37.4) and 183.1 (10.0) days, respectively. Inclisiran had significantly higher adherence and lower rates of discontinuation vs. anti-PCSK9 mAbs at 12-month after initiation. Convenient dosing of inclisiran may be an option for patients who requires additional LDL-C lowering. [ABSTRACT FROM AUTHOR]

This study aimed to determine the relationship between bilirubin levels and carotid atherosclerosis (CAS) in the health screening population. After propensity score matching, this retrospective cohort study included 4360 subjects who underwent health examinations regularly in Hebei General Hospital between January 2010 and December 2019 and had no carotid plaque at baseline. After an average follow-up of 26.76 months, the main endpoint Cox regression analysis of carotid plaques was performed. After adjusting the confounding factors, Cox regression analysis showed that when serum total bilirubin (TBIL) and unconjugated bilirubin (UCB) increased by 1 standard deviation (SD), the risk of carotid plaque decreased by 7.30% (95% confidence interval (CI): 2.80–11.60%) and 15.70% (95% CI: 11.40–19.80%), respectively. When conjugated bilirubin (CB) increased by 1 SD, the risk of carotid plaques increased by 24.3% (95% CI: 19.7–29.0%). TBIL and UCB levels were negatively associated with CAS, and CB levels were positively associated with CAS. [ABSTRACT FROM AUTHOR]

Green pepper (Capsicum annuum L.) is one of the major vegetables cultivated in sub-tropical monsoon climate regions. However, with the unreasonable use of water and nitrogen (N) fertilizer, efficient water and N fertilizer management systems need to be identified. The goal of this project was to investigate the coupling effects of different amounts of water and N on green pepper yield, water use efficiency (WUE), as well as N use efficiency (NUE) in sub-tropical monsoon climate regions. The optimum combination of water and N inputs was determined for multi-objective optimization through the multiple regression analysis and the combinations of likelihood functions. The pot experiment was conducted during the green pepper growing seasons (May–September) of 2019 and 2020 in a greenhouse at Nanchang, Jiangxi of China that included three water deficit levels, i.e., mild deficit (W1: 95~80%θFC, %θ field capacity simplified as %θFC), moderate deficit (W2: 80~65%θFC), and severe deficit (W3: 65~50%θFC), and four levels of nitrogen application (Napp) rate, i.e., 6.0 (N1), 3.0 (N2), 1.5 (N3), and 0.0 g plant−1 (N4), for a total of twelve treatments (i.e., 3 × 4) with six replications. Results show that water levels have an extremely significant effect (p < 0.01) on green pepper yield and WUE, but no effect on NUE (p > 0.05). N treatments have significant effects on green pepper yield, WUE, and NUE. Meanwhile, the effects of water levels and N treatment interaction on WUE and NUE were extremely significant (p < 0.01), but varied on yield between the two years. The maximum yields (576.26 and 619.00 g plant−1) occurred when the water level and Napp rate were 80~65%θFC and 6.0 g plant−1. While the water level and Napp rate were 80~65%θFC and 3.0 g plant−1, the WUEs and NUEs reached the maximum, which were 20.14 and 17.71 g L−1, 76.54, and 77.73 g−1 in 2019 and 2020. The dualistic and quadric regression equations of irrigation amount and Napp rate indicated that the yield, WUE and NUE cannot reach the maximum at the same time. By establishing a multiobjective optimization model using combinations of likelihood functions, it was concluded that the water level shall be controlled in 80~65%θFC and the Napp rate is 3.78 g plant−1, which can be used as the suitable strategy of water and N management for the maximum comprehensive benefits of yield, WUE, and NUE for green pepper. The obtained optimum combination of water and N inputs can provide a scientific basis for irrigation and fertilization optimization and management in sub-tropical monsoon climate regions. [ABSTRACT FROM AUTHOR]

Background: The current study set out to probe the function of different doses of ketamine in postoperative neurocognitive disorder (PND) in aged mice undergoing partial hepatectomy (PH) with the involvement of the brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1)/n-methyl-D-aspartate (NMDA)/nuclear factor-kappa B (NF-κB) axis. Methods: First, aged mice were intraperitoneally injected with different doses of ketamine prior to surgery, followed by hepatic lobectomy. Afterward, mice cognitive function was assessed. In addition, Bmal1 mRNA expression patterns were quantified, while NMDA 2B receptor, NF-κB p65, synapsin 1, and postsynaptic density 95 (PSD95) levels were determined; the release of inflammatory factors was detected, and ionized calcium-binding adapter molecule-1 expression was measured to quantify microglia activation. In addition, Bmal1-knockout (Bmal1-KO) mice were intraperitoneally injected with a subanesthetic dose of ketamine to verify the mechanism of Bmal1 in regulating the NMDA 2B subunit (NR2B)/NF-κB axis to affect PH in aged patients. Results: After PH, hippocampal-dependent memory was impaired, and synapsin 1 and PSD95 levels were downregulated. On the other hand, PH diminished Bmal1 expression but elevated NR2B and NF-κB p65 levels and anesthetic doses of ketamine further regulated the Bmal1/NMDA/NF-κB axis. In Bmal1-KO mice, the NMDA/NF-κB axis was activated, the release of inflammatory cytokines was promoted, and hippocampus-dependent memory was impaired, which were reversed by a subanesthetic dose of ketamine. Conclusion: Altogether, findings obtained in our study indicated that a subanesthetic dose of ketamine activated Bmal1, downregulated the NMDA/NF-κB axis, and reduced inflammation and microglia activation to alleviate PND in aged mice undergoing PH. [ABSTRACT FROM AUTHOR]