Characterisation of Death Receptor 3 dependent aortic changes during inflammatory arthritis

Murine collagen‐induced arthritis (mCIA) is characterized by decreased vascular constriction responses and increased MMP‐9. Here, we describe additional histological alterations within the aorta and surrounding perivascular adipose tissue (PVAT), study the role of PVAT in constriction response, and investigate the potential involvement of death receptor 3 (DR3). mCIA was induced in wild‐type (WT) and DR3−/− mice with nonimmunized, age‐matched controls. Vascular function was determined in isolated aortic rings ±PVAT, using isometric tension myography, in response to cumulative serotonin concentrations. Cellular expression of F4/80 (macrophages), Ly6G (neutrophils), DR3, and MMP‐9 was determined using immunohistochemistry. In WTs, arthritis‐induced vascular dysfunction was associated with increased F4/80+ macrophages and increased DR3 expression in the aorta and PVAT. MMP‐9 was also up‐regulated in PVAT, but did not correlate with alterations of PVAT intact constriction. DR3−/− mice inherently showed increased leukocyte numbers and MMP‐9 expression in the PVAT, but retained the same nonarthritic constriction response as DR3WT mice ±PVAT. Arthritic DR3−/− mice had a worsened constriction response than DR3WT and showed an influx of neutrophils to the aorta and PVAT. Macrophage numbers were also up‐regulated in DR3−/− PVAT. Despite this influx, PVAT intact DR3−/− constriction responses were restored to the same level as DR3WT. Impaired vascular constriction in inflammatory arthritis occurs independently of total MMP‐9 levels, but correlates with macrophage and neutrophil ingress. Ablating DR3 worsens the associated vasculature dysfunction, however, DR3−/− PVAT is able to protect the aorta against aberrant vasoconstriction caused in this model

PLATFORM HEIGHT FOR DROP JUMP DETERMINED BY COUNTER MOVEMENT JUMP

The purpose of the study was to apply personal counter movement jump (CMJ) ability as a standard of choosing the height of the platform and to analyze the kinematics and kinetics during DJ in order to find the appropriate height of the platform for an individual. Twenty male Division I college volleyball players were the participants. Data were collected using 11 infrared Eagle cameras and two AMTI force platforms. The major finding was that the personalized platform height designed according to personal jumping ability showed significant increase in the impulse of eccentric phase during the drop height being above 100%CMJ. The platform height chosen according to 100%CMJ would be an appropriate height for an individual

Oxysterols protect bovine endometrial cells against pore‐forming toxins from pathogenic bacteria

Many species of pathogenic bacteria secrete toxins that form pores in mammalian cell membranes. These membrane pores enable the delivery of virulence factors into cells, result in the leakage of molecules that bacteria can use as nutrients, and facilitate pathogen invasion. Inflammatory responses to bacteria are regulated by the side-chain-hydroxycholesterols 27-hydroxycholesterol and 25-hydroxycholesterol, but their effect on the intrinsic protection of cells against pore-forming toxins is unclear. Here, we tested the hypothesis that 27-hydroxycholesterol and 25-hydroxycholesterol help protect cells against pore-forming toxins. We treated bovine endometrial epithelial and stromal cells with 27-hydroxycholesterol or 25-hydroxycholesterol, and then challenged the cells with pyolysin, which is a cholesterol-dependent cytolysin from Trueperella pyogenes that targets these endometrial cells. We found that treatment with 27-hydroxycholesterol or 25-hydroxycholesterol protected both epithelial and stomal cells against pore formation and the damage caused by pyolysin. The oxysterols limited pyolysin-induced leakage of potassium and lactate dehydrogenase from cells, and reduced cytoskeletal changes and cytolysis. This oxysterol cytoprotection against pyolysin was partially dependent on reducing cytolysin-accessible cholesterol in the cell membrane and on activating liver X receptors. Treatment with 27-hydroxycholesterol also protected the endometrial cells against Staphylococcus aureus α hemolysin. Using mass spectrometry, we found 27-hydroxycholesterol and 25-hydroxycholesterol in uterine and follicular fluid. Furthermore, epithelial cells released additional 25-hydroxycholesterol in response to pyolysin. In conclusion, both 27-hydroxycholesterol and 25-hydroxycholesterol increased the intrinsic protection of bovine endometrial cells against pore-forming toxins. Our findings imply that side-chain-hydroxycholesterols may help defend the endometrium against pathogenic bacteria

A delayed differentiation multi-product FPR model with scrap and a multi-delivery policy – I: Using single-machine production scheme

This study examines a delayed differentiation multi-product single-machine finite production rate (FPR) model with scrap and a multi-delivery policy. The classic FPR model considers a single product, single stage production with all items manufactured being of perfect quality and product demand satisfied by a continuous inventory issuing policy. However, in real-life production-shipment integrated systems, multi-product production is usually adopted by vendors to maximize machine utilization, and generation of scrap items appear to be inevitable with uncontrollable factors in production. Further, distribution of finished products is often done through a periodic or multi-delivery policy rather than a continuous issuing policy. It is also assumed that these multiple products share a common intermediate part. In this situation, the producer would often be interested in evaluating a two-stage production scheme with the first stage producing common parts for all products and the second stage separately fabricating the end products to lower overall production-inventory costs and shorten the replenishment cycle time. Redesigning a multi-product FPR system to delay product differentiation to the final stage of production has proved to be an effective supply chain strategy from an inventory-reduction standpoint. Using mathematical modelling, we derive the optimal replenishment cycle time and delivery policy. A numerical example is provided to demonstrate its practical usage and compare our result to that obtained from the traditional single-stage multi-product FPR model

Optimizing Error-Bounded Lossy Compression for Three-Dimensional Adaptive Mesh Refinement Simulations

Today's scientific simulations require a significant reduction of data volume because of extremely large amounts of data they produce and the limited I/O bandwidth and storage space. Error-bounded lossy compression has been considered one of the most effective solutions to the above problem. However, little work has been done to improve error-bounded lossy compression for Adaptive Mesh Refinement (AMR) simulation data. Unlike the previous work that only leverages 1D compression, in this work, we propose to leverage high-dimensional (e.g., 3D) compression for each refinement level of AMR data. To remove the data redundancy across different levels, we propose three pre-process strategies and adaptively use them based on the data characteristics. Experiments on seven AMR datasets from a real-world large-scale AMR simulation demonstrate that our proposed approach can improve the compression ratio by up to 3.3X under the same data distortion, compared to the state-of-the-art method. In addition, we leverage the flexibility of our approach to tune the error bound for each level, which achieves much lower data distortion on two application-specific metrics.Comment: 13 pages, 17 figures, 3 tables, accepted by ACM HPDC 202

Predictors of switching from beta-blockers to other anti-hypertensive drugs: a review of records of 19,177 Chinese patients seen in public primary care clinics in the New Territory East, Hong Kong

Background: Beta-blocker drugs are commonly used in family practice and studies showed that they were the most popularly prescribed medications among all antihypertensive agents. This study aimed to identify the factors associated with medication switching from a beta-blocker to another antihypertensive drug among Chinese patients. Methods: We used a validated database which consisted of the demographic and clinical information of all Chinese patients prescribed a beta-blocker from any public, family practice clinics between 01 Jan 2004 to 30 June 2007 in one large Territory of Hong Kong. The proportion of patients switched from beta-blockers to another antihypertensive agent 180 days within their first prescription was studied, and the factors associated with medication switching were evaluated by using multivariate regression analyses. Results: From 19,177 eligible subjects with a mean age of 59.1 years, 763 (4.0%) were switched from their beta-blockers within 180 days of commencing therapy. A binary logistic regression model used medication switching as the outcome variable and controlled for age, gender, socioeconomic status, clinic setting (general out-patient clinics, family medicine specialist clinic or staff clinics), district of residence, visit type (new vs. follow-up attendance), the number of concomitant co-morbidities, and the calendar year of prescription. It was found that older patients (age 50-59 years: adjusted odds ratio [AOR] 1.38, 95% C.I. 1.12-1.70; p = 0.002; age 60-69 years: AOR 1.63 95% C.I. 1.30-2.04, p < 0.001; age ≥ 70 years: AOR 1.82, 95% C.I. 1.46-2.26, p < 0.001; referent age < 50 years) and new visitors (AOR 0.57, 95% C.I. 0.48-0.68, p < 0.001) were more likely to have their medication switched. Conclusions: Closer monitoring of the medication taking behavior among the older patients and the new clinic visitors prescribed a beta-blocker is warranted. Future studies should evaluate the reasons of drug switching

Epidemiology of multimorbidity in China and implications for the healthcare system: cross-sectional survey among 162,464 community household residents in southern China

<b>Background</b> China, like other countries, is facing a growing burden of chronic disease but the prevalence of multimorbidity and implications for the healthcare system have been little researched. We examined the epidemiology of multimorbidity in southern China in a large representative sample. The effects of multimorbidity and other factors on usual source of healthcare were also examined. <p></p> <b>Methods</b> We conducted a large cross-sectional survey among approximately 5% (N = 162,464) of the resident population in three prefectures in Guangdong province, southern China in 2011. A multistage, stratified random sampling was adopted. The study population had many similar characteristics to the national census population. Interviewer-administered questionnaires were used to collect self-report data on demographics, socio-economics, lifestyles, healthcare use, and health characteristics from paper-based medical reports. <p></p> <b>Results</b> More than one in ten of the total study population (11.1%, 95% confidence interval (CI) 10.6 to 11.6) had two or more chronic conditions from a selection of 40 morbidities. The prevalence of multimorbidity increased with age (adjusted odds ratio (aOR) = 1.36, 95% CI 1.35 to 1.38 per five years). Female gender (aOR = 1.70, 95% CI 1.64 to 1.76), low education (aOR = 1.26, 95% CI 1.23 to 1.29), lack of medical insurance (aOR = 1.79, 95% CI 1.71 to 1.89), and unhealthy lifestyle behaviours were independent predictors of multimorbidity. Multimorbidity was associated with the regular use of secondary outpatient care in preference to primary care. <p></p> <b>Conclusions</b> Multimorbidity is now common in China. The reported preferential use of secondary care over primary care by patients with multimorbidity has many major implications. There is an urgent need to further develop a strong and equitable primary care system

Reduction of secondary electron yield for E-cloud mitigation laser ablation surface engineering

Developing a surface with low Secondary Electron Yield (SEY) is one of the main ways of mitigating electron cloud and beam-induced electron multipacting in high-energy charged particle accelerators. In our previous publications, a low SEY < 0.9 for as-received metal surfaces modified by a nanosecond pulsed laser was reported. In this paper, the SEY of laser-treated blackened copper has been investigated as a function of different laser irradiation parameters. We explore and study the influence of micro- and nano-structures induced by laser surface treatment in air of copper samples as a function of various laser irradiation parameters such as peak power, laser wavelength (λ = 355 nm and 1064 nm), number of pulses per point (scan speed and repetition rate) and fluence, on the SEY. The surface chemical composition was determined by x-ray photoelectron spectroscopy (XPS) which revealed that heating resulted in diffusion of oxygen into the bulk and induced the transformation of CuO to sub-stoichiometric oxide. The surface topography was examined with high resolution scanning electron microscopy (HRSEM) which showed that the laser-treated surfaces are dominated by microstructure grooves and nanostructure features