3,882 research outputs found

    Two Years Later: Journals Are Not Yet Enforcing the ARRIVE Guidelines on Reporting Standards for Pre-Clinical Animal Studies

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    There is growing concern that poor experimental design and lack of transparent reporting contribute to the frequent failure of pre-clinical animal studies to translate into treatments for human disease. In 2010, the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were introduced to help improve reporting standards. They were published in PLOS Biology and endorsed by funding agencies and publishers and their journals, including PLOS, Nature research journals, and other top-tier journals. Yet our analysis of papers published in PLOS and Nature journals indicates that there has been very little improvement in reporting standards since then. This suggests that authors, referees, and editors generally are ignoring guidelines, and the editorial endorsement is yet to be effectively implemented

    Differentiation of adult-type Leydig cells occurs in gonadotrophin-deficient mice

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    During mammalian testis development distinct generations of fetal and adult Leydig cells arise. Luteinising hormone (LH) is required for normal adult Leydig cell function and for the establishment of normal adult Leydig cell number but its role in the process of adult Leydig cell differentiation has remained uncertain. In this study we have examined adult Leydig cell differentiation in gonadotrophin-releasing hormone (GnRH)-null mice which are deficient in circulating gonadotrophins. Adult Leydig cell differentiation was assessed by measuring expression of mRNA species encoding four specific markers of adult Leydig cell differentiation in the mouse. Each of these markers (3β-hydroxysteroid dehydrogenase type VI (3βHSD VI), 17β-hydroxysteroid dehydrogenase type III (17βHSD III), prostaglandin D (PGD)-synthetase and oestrogen sulphotransferase (EST)) is expressed only in the adult Leydig cell lineage in the normal adult animal. Real-time PCR studies showed that all four markers are expressed in adult GnRH-null mice. Localisation of 3βHSD VI and PGD-synthetase expression by in situ hybridisation confirmed that these genes are expressed in the interstitial tissue of the GnRH-null mouse. Treatment of animals with human chorionic gonadotrophin increased expression of 3βHSD VI and 17βHSD III within 12 hours further indicating that differentiated, but unstimulated cells already exist in the GnRH-null mouse. Thus, while previous studies have shown that LH is required for adult Leydig cell proliferation and activity, results from the present study show that adult Leydig cell differentiation will take place in animals deficient in LH

    Mapping policies and programmes: the use of GIS to communicate spatial relationships in England

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    It has long been acknowledged that there is a gap between the advancement of GIS in the research field and its application in planning practice. This paper demonstrates the potential for employing simple GIS mapping overlays as a way of communicating complex planning issues in a ‘language’ that is easily understandable and effective at stimulating policy debate, critical thinking and learning. The analysis focuses on capturing the synergies and conflicts in two key planning challenges in England, progrowth and housing delivery agendas. In a political context where spatial evidencebased policymaking has been eroded in recent years, the analysis demonstrates the need for policymakers to ‘think spatially, act spatially’ when developing different policies and programmes. The paper concludes that only by making spatial relationships of policies and programmes explicit in a manner that is easily understood by a range of actors, can different spatial scenarios and metaphors of future opportunities and challenges be developed to inform long-range development and planning

    Problematic attention processing and fear learning in adolescent anxiety: Testing a combined cognitive and learning processes model

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    Newton Fund (managed by the UK Medical Research Council) (HB, VK, SN, JL) and the India Department of Biotechnology (RP

    The retreat from widening participation? : the National Scholarship Programme and new access agreements in English higher education

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    This article critically analyses the impact of reforms to the student financial support system in English higher education. Comparative analysis of financial support mechanisms and patterns of outreach engagement with groups underrepresented in higher education show a marked deterioration in the levels of cash support available and an increasingly focus on the brightest poor students (in the form of merit aid) at the expense of the generality of poorer students since the new support programme came into place. This can be seen as part of a wider policy shift away from generic widening participation to the targeting of specific cohorts to raise the attainment level of intakes or to meet recruitment shortfalls. The findings are located in a context of a (near) trebling of tuition fees, stagnation in overall student numbers and the promotion of market mechanisms, all of which can be seen as a challenge to the notion of social justice through the higher education system

    A heart failure self-management program for patients of all literacy levels: A randomized, controlled trial [ISRCTN11535170]

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    BACKGROUND: Self-management programs for patients with heart failure can reduce hospitalizations and mortality. However, no programs have analyzed their usefulness for patients with low literacy. We compared the efficacy of a heart failure self-management program designed for patients with low literacy versus usual care. METHODS: We performed a 12-month randomized controlled trial. From November 2001 to April 2003, we enrolled participants aged 30–80, who had heart failure and took furosemide. Intervention patients received education on self-care emphasizing daily weight measurement, diuretic dose self-adjustment, and symptom recognition and response. Picture-based educational materials, a digital scale, and scheduled telephone follow-up were provided to reinforce adherence. Control patients received a generic heart failure brochure and usual care. Primary outcomes were combined hospitalization or death, and heart failure-related quality of life. RESULTS: 123 patients (64 control, 59 intervention) participated; 41% had inadequate literacy. Patients in the intervention group had a lower rate of hospitalization or death (crude incidence rate ratio (IRR) = 0.69; CI 0.4, 1.2; adjusted IRR = 0.53; CI 0.32, 0.89). This difference was larger for patients with low literacy (IRR = 0.39; CI 0.16, 0.91) than for higher literacy (IRR = 0.56; CI 0.3, 1.04), but the interaction was not statistically significant. At 12 months, more patients in the intervention group reported monitoring weights daily (79% vs. 29%, p < 0.0001). After adjusting for baseline demographic and treatment differences, we found no difference in heart failure-related quality of life at 12 months (difference = -2; CI -5, +9). CONCLUSION: A primary care-based heart failure self-management program designed for patients with low literacy reduces the risk of hospitalizations or death

    Effects of Smoking and Cessation on Subclinical Arterial Disease: A Substudy of a Randomized Controlled Trial

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    The mechanisms by which smoking cessation reduces cardiovascular disease risk are unclear. We evaluated longitudinal changes in carotid intima-media thickness among current smokers enrolled in a prospective, randomized smoking cessation clinical trial.Subjects were enrolled in a randomized, double-blind, placebo-controlled trial of 5 smoking cessation pharmacotherapies and underwent carotid ultrasonography with carotid intima-media thickness measurement. Subjects were classified as continuously abstinent (biochemically confirmed abstinence at 6 months, 1 year, and 3 years post-quit attempt), intermittently abstinent (reported smoking at one of the three time points), or smoked continuously (reported smoking at all three time points). The primary endpoint was the absolute change (mm) in carotid intima-media thickness (ΔCIMT(max)) before randomization and 3 years after the target quit date. Pearson correlations were calculated and multivariable regression models (controlling for baseline CIMT(max) and research site) were analyzed. Among 795 subjects (45.2 ± 10.6 years old, 58.5% female), 189 (23.8%) were continuously abstinent, 373 (46.9%) smoked continuously, and 233 (29.3%) were abstinent intermittently. There was a greater increase in carotid intima-media thickness among subjects who were continuously abstinent than among those who smoked continuously (p = 0.020), but not intermittently (p = 0.310). Antihypertensive medication use (p = 0.001) and research site (p<0.001) independently predicted ΔCIMTmax--not smoking status. The greatest increase in carotid intima-media thickness among continuous abstainers was related to increases in body-mass index (p = 0.043).Smoking status did not independently predict ΔCIMT(max); increasing body-mass index and antihypertensive medication use were the most important independent predictors. The rapid reduction in cardiovascular disease events observed with smoking cessation is unlikely to be mediated by changes in subclinical atherosclerosis burden.ClinicalTrials.gov NCT00332644
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