25 research outputs found

    The enablers and barriers of providing professional practical skills education to rural elementary school students in Zhejiang, China

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    Professional technical skills (technical skills) and professional practical skills (practical skills) are two kinds of education that are often discussed in terms of technical knowledge and life skills respectively. The acquisition of both technical and practical skills not only is the outcome of education, but also is required by a market economy. However, Chinese rural students are not provided practical skills under the traditional exam-oriented educational system. This study argues to build the educational infrastructure in rural China to provide both kinds of skills to improve the quality of its rural human resources;The purpose of this study is to investigate the feasibility of providing practical skills and technical skills education to rural elementary school students under the exam-oriented education philosophy, and then to make recommendation regarding the design for appropriate educational programs. The researcher used a descriptive design, including both qualitative and quantitative research methods, to investigate the enablers and barriers to providing both technical and practical skills education to rural elementary school students in Zhejiang, China. Specifically, the researcher conducted focus groups and survey with rural elementary school teachers, students, and the students\u27 parents. The data indicated three enablers, which are: (1) teachers and parents overwhelmingly agreed on the importance of providing practical skills education to rural elementary school students; (2) teachers and parents showed their willingness to participate in the study and potential subsequent projects aimed toward building the infrastructure for practical skills education; and (3) students would enjoy learning practical skills together with technical skills because of their preference on the learning practice that is informed by the educational theory that supports the providing of both skills. However, the data also revealed three barriers to this process: (1) the traditional exam-oriented educational philosophy in China; (2) only schools are responsible for providing education; and (3) financial issues. The researcher also recognized a lack of effective communication between the schools and the families. In the end, the researcher recommended setting up a cooperative education system to provide nonformal educational programs, such as 4-H-type programs, based on an experiential theoretical base and the it takes a village Philosophy

    Loss of Regulator of G Protein Signaling 5 Exacerbates Obesity, Hepatic Steatosis, Inflammation and Insulin Resistance

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    BACKGROUND: The effect of regulator of G protein signaling 5 (RGS5) on cardiac hypertrophy, atherosclerosis and angiogenesis has been well demonstrated, but the role in the development of obesity and insulin resistance remains completely unknown. We determined the effect of RGS5 deficiency on obesity, hepatic steatosis, inflammation and insulin resistance in mice fed either a normal-chow diet (NC) or a high-fat diet (HF). METHODOLOGY/PRINCIPAL FINDINGS: Male, 8-week-old RGS5 knockout (KO) and littermate control mice were fed an NC or an HF for 24 weeks and were phenotyped accordingly. RGS5 KO mice exhibited increased obesity, fat mass and ectopic lipid deposition in the liver compared with littermate control mice, regardless of diet. When fed an HF, RGS5 KO mice had a markedly exacerbated metabolic dysfunction and inflammatory state in the blood serum. Meanwhile, macrophage recruitment and inflammation were increased and these increases were associated with the significant activation of JNK, IκBα and NF-κBp65 in the adipose tissue, liver and skeletal muscle of RGS5 KO mice fed an HF relative to control mice. These exacerbated metabolic dysfunction and inflammation are accompanied with decreased systemic insulin sensitivity in the adipose tissue, liver and skeletal muscle of RGS5 KO mice, reflected by weakened Akt/GSK3β phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that loss of RGS5 exacerbates HF-induced obesity, hepatic steatosis, inflammation and insulin resistance

    Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

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    Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe

    The enablers and barriers of providing professional practical skills education to rural elementary school students in Zhejiang, China

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    Professional technical skills (technical skills) and professional practical skills (practical skills) are two kinds of education that are often discussed in terms of technical knowledge and life skills respectively. The acquisition of both technical and practical skills not only is the outcome of education, but also is required by a market economy. However, Chinese rural students are not provided practical skills under the traditional exam-oriented educational system. This study argues to build the educational infrastructure in rural China to provide both kinds of skills to improve the quality of its rural human resources;The purpose of this study is to investigate the feasibility of providing practical skills and technical skills education to rural elementary school students under the exam-oriented education philosophy, and then to make recommendation regarding the design for appropriate educational programs. The researcher used a descriptive design, including both qualitative and quantitative research methods, to investigate the enablers and barriers to providing both technical and practical skills education to rural elementary school students in Zhejiang, China. Specifically, the researcher conducted focus groups and survey with rural elementary school teachers, students, and the students' parents. The data indicated three enablers, which are: (1) teachers and parents overwhelmingly agreed on the importance of providing practical skills education to rural elementary school students; (2) teachers and parents showed their willingness to participate in the study and potential subsequent projects aimed toward building the infrastructure for practical skills education; and (3) students would enjoy learning practical skills together with technical skills because of their preference on the learning practice that is informed by the educational theory that supports the providing of both skills. However, the data also revealed three barriers to this process: (1) the traditional exam-oriented educational philosophy in China; (2) only schools are responsible for providing education; and (3) financial issues. The researcher also recognized a lack of effective communication between the schools and the families. In the end, the researcher recommended setting up a cooperative education system to provide nonformal educational programs, such as 4-H-type programs, based on an experiential theoretical base and the it takes a village Philosophy;</p

    RGS5 deletion resulted in decreased peripheral insulin sensitivity and suppressed the Akt/GSK3β signaling pathway in mice fed an HF for 24 weeks.

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    <p><b>A,B,C</b> Blood glucose levels during GTT were determined at the indicated time points after i.p. injection with a bolus of glucose in WT and KO mice fed an NC (A) and HF (B) and corresponding AUC (C) (n = 6–8). <b>D,E,F</b> Blood glucose levels during ITT were determined at the indicated time points after i.p. injection with a bolus of insulin in WT and KO mice fed an NC (D) and HF (E) and corresponding AUC (F) (n = 6–8). <b>G</b> Phosphorylation levels of proteins related to insulin signaling in the visceral adipose tissue, liver and gastrocnemius muscle of WT and KO mice (n = 6). <b>H</b> Quantitative measurements of p-Akt and p-GSK3β protein relative to their total protein between WT mice (a dotted line at value 1) and KO mice (black). Values represent means ± SEM. #<i>p</i><0.05 and ##<i>p</i><0.01 compared with WT mice fed an NC; *<i>p</i><0.05 and **<i>p</i><0.01 compared with WT mice fed an HF.</p

    RGS5 deficiency exacerbated hyperinsulinemia.

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    <p><b>A</b> The level of fasting blood glucose in WT (black) and KO (blank) mice fed an NC (triangle) and HF (rhombus) from 0 to 24 weeks (n = 8–11). <b>B,C</b> The level of plasma insulin in WT (black) and KO (blank) mice fed an NC(triangle) and HF (rhombus) from 0 to 24 weeks (B) and corresponding AUC (C) (n = 8). Values represent means ± SEM. #<i>p</i><0.05 and ##<i>p</i><0.01 compared with WT mice fed an NC; *<i>p</i><0.05 and **<i>p</i><0.01 compared with WT mice fed an HF.</p

    RGS5 deficiency exacerbated fat accumulation in liver.

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    <p><b>A</b> Histology of liver with hematoxylin-eosin. <b>B</b> Histology of liver with oil red O. <b>C</b> Expression levels of mRNA related to fatty acid metabolism in the liver of WT (a dotted line at value 1) and KO (black) mice fed an HF for 24 weeks (n = 6). Values represent means ± SEM. *<i>p</i><0.05 and **<i>p</i><0.01 compared with WT mice.</p

    Effect of RGS5 deficiency on body weight, fat mass and adipocyte size.

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    <p><b>A</b> Representative photograph of WT and KO mice fed an NC and HF for 24 weeks. <b>B</b> Growth curves of WT (black) and KO (blank) mice fed an NC (triangle) and an HF (rhombus) (n = 8–11). <b>C</b> Histology of visceral adipose tissue with hematoxylin-eosin. <b>D</b> Mean adipocyte size of the visceral adipose tissue in WT (black) and KO (blank) mice fed an NC and an HF for 24 weeks (n = 5). <b>E</b> Expression levels of mRNA related to adipogenesis in the visceral fat of WT (a dotted line at value 1) and KO (black) mice fed an HF for 24 weeks (n = 6). Values represent means ± SEM. #<i>p</i><0.05 and ##<i>p</i><0.01 compared with WT mice fed an NC; *<i>p</i><0.05 and **<i>p</i><0.01 compared with WT mice fed an HF.</p
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