Background: Prescribing of antibiotics for viral upper respiratory infection (URI) remains a pressing public health problem. We sought to reduce inappropriate prescribing of antibiotics for viral URIs at primary-care practices at Mayo Clinic Arizona (MCA). Methods: Diagnostic codes for URIs commonly caused by viruses were categorized as tier 3 (ie, never prescribe). The inappropriate prescribing rate was defined as the number of tier 3 encounters resulting in a prescription for a URI antibiotic divided by the total number of tier 3 encounters. MCA primary-care departments, including family medicine, community internal medicine, emergency medicine, and women’s health internal medicine, were included in the intervention. Each department was briefed on the project, including baseline department prescribing data, and was provided education. Education topics included appropriate indications for antibiotics, patient-centered strategies for reducing antibiotic use, and a review of electronic resources developed specifically for the project. Resources included a syndromic ambulatory order panel (EZ ID Respiratory Order Panel) and a viral prescription pad, which contains simplified over-the-counter recommendations for symptomatic management of viral URIs and patient education. Quarterly peer comparison reports were provided to the department chairs and/or site leads. Our goal was to reduce inappropriate prescribing by 22% in 2022. An Epic dashboard (SlicerDicer model) was developed to track data on an ongoing basis. We used χ2 tests to compare categorical variables. Results: Department education was completed by June 2022 (Fig. 1). The annual antibiotic prescribing rate for tier 3 encounters decreased by 29% from a baseline rate 23.6% in 2021 to 16.4% in 2022 (P < .001). The posteducation prescribing rate (June 2022–December 2022) was 13.1%. Utilization of the EZ ID ambulatory order panel increased from an average of 1.5 uses per month in 2021 to 13.3 uses per month in 2022 (Fig. 2). Repeated healthcare contact for URIs within 14 days of tier 3 encounters did not differ among patients prescribed and not prescribed an antibiotic in all of 2022 (3.8% vs 3.9%; P = .91) or during the posteducation period (1.8% vs 4.2%; P = .14). There was no appreciable diagnostic shift over the course of 2022 (Fig. 3). Conclusions: A multifaceted intervention, which included baseline education, promotion of syndrome-specific order panels, dissemination of resources for symptomatic management, and distribution of peer comparison reports, resulted in significant reduction of inappropriate antibiotic prescribing for URIs.

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In this paper, we consider a general single population model with delay and patch structure, which could model the population loss during the dispersal. It is shown that the model admits a unique positive equilibrium when the dispersal rate is smaller than a critical value. The stability of the positive equilibrium and associated Hopf bifurcation are investigated when the dispersal rate is small or near the critical value. Moreover, we show the effect of network topology on Hopf bifurcation values for a delayed logistic population model.

Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.

There are various matrices to represent parallel mechanisms. It is essential to design a kind of approach to not only denote the parallel structures but also disclose the joint directions. In this paper, a novel methodology called the kinematic joint matrix (KJM) is proposed. It possesses the mapping relations with parallel manipulators with three kinds of kinematic joints. The size of such matrix is smaller when compared with that of topology matrix. A series of two to six degrees-of-freedom parallel architectures is denoted by the KJM. A convenient approach using a special block diagram is introduced to distinguish various kinds of kinematic joint matrices. In addition, detailed comparisons between KJM and topology matrix are investigated. Three regulations are proposed for the latter to be applicable to parallel mechanisms.

This study was aimed to investigate whether EPA and arachidonic acid (ARA), the representative n-3 or n-6 PUFA, could alleviate enterotoxigenic Escherichia coli (ETEC) K88-induced inflammation and injury of intestinal porcine epithelial cells 1 (IPEC-1) by modulating pyroptosis and necroptosis signalling pathways. IPEC-1 cells were cultured with or without EPA or ARA in the presence or absence of ETEC K88. EPA and ARA reduced ETEC K88 adhesion and endotoxin content in the supernatant. EPA and ARA increased transepithelial electrical resistance, decreased permeability of fluorescein isothiocyanate-labelled dextran, increased membrane protein expression of occludin, ZO-1 and claudin-1 and relieved disturbed distribution of these proteins. EPA and ARA also reduced cell necrosis ratio. EPA or ARA reduced mRNA and concentration of TNF-α, IL-6 and IL-8 and decreased mRNA abundances of intestinal toll-like receptors 4 and its downstream signals. Moreover, EPA and ARA downregulated mRNA expression of nod-like receptor protein 3 (NLRP3), caspase 1 and IL-18 and inhibited protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), gasdermin D and caspase-1. Finally, EPA and ARA reduced mRNA expression of fas-associated death domain protein, caspase 8, receptor-interacting protein kinase (RIP) 1, mixed lineage kinase-like protein (MLKL), phosphoglycerate mutase 5 (PGAM5), motility-related protein 1 (Drp1) and high mobility protein 1 (HMGB1) and inhibited protein expression of phosphorylated-RIP1, p-RIP3, p-MLKL and HMGB1. These data demonstrate that EPA and ARA prevent ETEC K88-induced cell inflammation and injury, which is partly through inhibiting pyroptosis and necroptosis signalling pathways.

Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (P for interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.

The effect of vitamin D (VD) on the risk of preeclampsia (PE) is uncertain. Few of previous studies focused on the relationship between dietary VD intake and PE risk. Therefore, we conducted this 1:1 matched case–control study to explore the association of dietary VD intake and serum VD concentrations with PE risk in Chinese pregnant women. A total of 440 pairs of participants were recruited during March 2016 to June 2019. Dietary information was obtained using a seventy-eight-item semi-quantitative FFQ. Serum concentrations of 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography–tandem MS. Multivariate conditional logistic regression was used to estimate OR and 95 % CI. Restricted cubic splines (RCS) were plotted to evaluate the dose–response relationship of dietary VD intake and serum VD concentrations with PE risk. Compared with the lowest quartile, the OR of the highest quartile were 0·45 (95 % CI 0·29, 0·71, Ptrend = 0·001) for VD dietary intake and 0·26 (95 % CI 0·11, 0·60, Ptrend = 0·003) for serum levels after adjusting for confounders. In addition, the RCS analysis suggested a reverse J-shaped relationship between dietary VD intake and PE risk (P-nonlinearity = 0·02). A similar association was also found between serum concentrations of total 25(OH)D and PE risk (P-nonlinearity = 0·02). In conclusion, this study provides evidence that higher dietary intake and serum levels of VD are associated with the lower risk of PE in Chinese pregnant women.

Malnutrition and acute kidney injury (AKI) are common complications in hospitalised patients, and both increase mortality; however, the relationship between them is unknown. This is a retrospective propensity score matching study enrolling 46 549 inpatients, aimed to investigate the association between Nutritional Risk Screening 2002 (NRS-2002) and AKI and to assess the ability of NRS-2002 and AKI in predicting prognosis. In total, 37 190 (80 %) and 9359 (20 %) patients had NRS-2002 scores <3 and ≥3, respectively. Patients with NRS-2002 scores ≥3 had longer lengths of stay (12·6 (sd 7·8) v. 10·4 (sd 6·2) d, P < 0·05), higher mortality rates (9·6 v. 2·5 %, P < 0·05) and higher incidence of AKI (28 v. 16 %, P < 0·05) than patients with normal nutritional status. The NRS-2002 showed a strong association with AKI, that is, the risk of AKI changed in parallel with the score of the NRS-2002. In short- and long-term survival, patients with a lower NRS-2002 score or who did not have AKI achieved a significantly lower risk of mortality than those with a high NRS-2002 score or AKI. Univariate Cox regression analyses indicated that both the NRS-2002 and AKI were strongly related to long-term survival (AUC 0·79 and 0·71) and that the combination of the two showed better accuracy (AUC 0·80) than the individual variables. In conclusion, malnutrition can increase the risk of AKI and both AKI and malnutrition can worsen the prognosis that the undernourished patients who develop AKI yield far worse prognosis than patients with normal nutritional status.

Weed invasion is a prevailing problem in modestly managed lawns. Less attention has been given to the exploration of the role of arbuscular mycorrhizal fungi (AMF) under different invasion pressures from lawn weeds. We conducted a four-season investigation into a Zoysia tenuifolia Willd. ex Thiele (native turfgrass)–threeflower beggarweed [Desmodium triflorum (L.) DC.] (invasive weed) co-occurring lawn. The root mycorrhizal colonizations of the two plants, the soil AM fungal communities and the spore densities under five different coverage levels of D. triflorum were investigated. Desmodium triflorum showed significantly higher root hyphal and vesicular colonizations than those of Z. tenuifolia, while the root colonizations of both species varied significantly among seasons. The increased coverage of D. triflorum resulted in the following effects: (1) the spore density initially correlated with mycorrhizal colonizations of Z. tenuifolia but gradually correlated with those of D. triflorum. (2) Correlations among soil properties, spore densities, and mycorrhizal colonizations were more pronounced in the higher coverage levels. (3) Soil AMF community compositions and relative abundances of AMF operational taxonomic units changed markedly in response to the increased invasion pressure. The results provide strong evidence that D. triflorum possessed a more intense AMF infection than Z. tenuifolia, thus giving rise to the altered host contributions to sporulation, soil AMF communities, relations of soil properties, spore densities, and root colonizations of the two plants, all of which are pivotal for the successful invasion of D. triflorum in lawns.

In this paper, we reported both the experimental demonstration and theoretical analysis of a Raman fiber laser based on a master oscillator–power amplifier configuration. The Raman fiber laser adopted the dual-wavelength bidirectional pumping configuration, utilizing 976 nm laser diodes and 1018 nm fiber lasers as the pump sources. A 60-m-long $25/400~\unicode[STIX]{x03BC}\text{m}$ ytterbium-doped fiber was used to convert the power from 1070 to 1124 nm, realizing a maximum power output of 3.7 kW with a 3 dB spectral width of 6.8 nm. Moreover, we developed a multi-frequency model taking into consideration the Raman gain spectrum and amplified spontaneous emission. The calculated spectral broadening of both the forward and backward laser was in good agreement with the experimental results. Finally, a 1.5 kW, 1183 nm second-order Raman fiber laser was further experimentally demonstrated by the addition of a 70-m-long germanium-doped passive fiber.

TiB2 particulates were formed in situ in an aluminum matrix via chemical reactions between an aluminum melt and the mixture of K2TiF6 and KBF4 salts. Different effects of Sc addition on the formation of the TiB2 particulates were revealed depending on the participation of Sc at different stages of the formation of the particulates. The metal–salt reactions resulted in boride layers along the α-Al grain boundaries in the presence of Sc, while the addition of Sc after the metal–salt reactions broke up the boride layers improving the dispersion of the TiB2 particulates to a limited degree. Sc promoted the growth of the TiB2 particulates, resulting in the coarsening of TiB2 particulates. The participation of Sc in the formation of TiB2 particulates altered the coarsening of the TiB2 particulates, resulting in different morphologies of the TiB2 particulates depending on the participation of Sc in the formation of the TiB2 particulates at different stages.

Dairy cows with type II ketosis display hepatic fat accumulation and hyperinsulinemia, but the underlying mechanism is not completely clear. This study aimed to clarify the regulation of lipid metabolism by insulin in cow hepatocytes. In vitro, cow hepatocytes were treated with 0, 1, 10, or 100 nm insulin in the presence or absence of AICAR (an AMP-activated protein kinase alpha (AMPKα) activator). The results showed that insulin decreased AMPKα phosphorylation. This inactivation of AMPKα increased the gene and protein expression levels of carbohydrate responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), which downregulated the expression of lipogenic genes, thereby decreasing lipid biosynthesis. Furthermore, AMPKα inactivation decreased the gene and protein expression levels of peroxisome proliferator-activated receptor-α (PPARα), which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation. In addition, insulin decreased the very low density lipoprotein (VLDL) assembly. Consequently, triglyceride content was significantly increased in insulin treated hepatocytes. Activation of AMPKα induced by AICAR could reverse the effect of insulin on PPARα, SREBP-1c, and ChREBP, thereby decreasing triglyceride content. These results indicate that insulin inhibits the AMPKα signaling pathway to increase lipid synthesis and decrease lipid oxidation and VLDL assembly in cow hepatocytes, thereby inducing TG accumulation. This mechanism could partly explain the causal relationship between hepatic fat accumulation and hyperinsulinemia in dairy cows with type II ketosis.

This paper presents a novel reconfigurable parallel mechanism, which can serve as a machine tool. The proposed parallel mechanism can change its structure parameters by driving a bevel gear system fixed in the base platform. First, the forward and inverse kinematics of the proposed mechanism are investigated. Second, the reachable workspace and Jacobian matrix are conducted. Based on the Jacobian matrix, the stiffness model and dexterity of the end effector are developed in detail. Finally, a multi-objective optimization is performed by using the Genetic Algorithm, and the workspace and global performance indexes of stiffness as well as the dexterity are considered as the performance indices to improve the performance of the reconfigurable parallel mechanism. Finally, Pareto frontier figure and several tables are provided to illustrate the results of the optimization. The results showed the proposed method has improved the performance of the reconfigurable machine tool in terms of its stiffness and dexterity.

Precipitates and grain sizes in non-oriented silicon steel samples, which were hot-rolled (HR), continuously annealed (CA), and stress-relief-annealed (SA), were characterized using scanning electron microscopy (SEM) equipped with electron back-scattered diffraction. The average grain sizes of the HR, CA, and SA samples were 28, 46, and 46 μm, respectively. SEM observations revealed that the precipitates were mainly dispersed inside grains in the HR and the CA samples, but mainly at grain boundaries in the SA sample. The density of precipitates was highest in the SA sample and lowest in the HR sample. Precipitates at the grain boundaries, which were identified as manganese sulfides, were nearly spherical, their diameter ranging from 0.3 to 0.7 μm. We calculated the pining force exerted by grain-boundary precipitates and found that it outweighed the driving force of the grain growth that was controlled by boundary curvature.