Coffee consumption and prostate cancer risk: further evidence for inverse relationship

<p>Abstract</p> <p>Background</p> <p>Higher consumption of coffee intake has recently been linked with reduced risk of aggressive prostate cancer (PC) incidence, although meta-analysis of other studies that examine the association between coffee consumption and overall PC risk remains inconclusive. Only one recent study investigated the association between coffee intake and grade-specific incidence of PC, further evidence is required to understand the aetiology of aggressive PCs. Therefore, we conducted a prospective study to examine the relationship between coffee intake and overall as well as grade-specific PC risk.</p> <p>Methods</p> <p>We conducted a prospective cohort study of 6017 men who were enrolled in the Collaborative cohort study in the UK between 1970 and 1973 and followed up to 31st December 2007. Cox Proportional Hazards Models were used to evaluate the association between coffee consumption and overall, as well as Gleason grade-specific, PC incidence.</p> <p>Results</p> <p>Higher coffee consumption was inversely associated with risk of high grade but not with overall risk of PC. Men consuming 3 or more cups of coffee per day experienced 55% lower risk of high Gleason grade disease compared with non-coffee drinkers in analysis adjusted for age and social class (HR 0.45, 95% CI 0.23-0.90, p value for trend 0.01). This association changed a little after additional adjustment for Body Mass Index, smoking, cholesterol level, systolic blood pressure, tea intake and alcohol consumption.</p> <p>Conclusion</p> <p>Coffee consumption reduces the risk of aggressive PC but not the overall risk.</p

Engaging with assessment: increasing student engagement through continuous assessment

Student engagement is intrinsically linked to two important metrics in learning: student satisfaction and the quality of the student experience. One of the ways that engagement can be influenced is through careful curriculum design. Using the knowledge that many students are ‘assessment-driven’ a low stakes continuous weekly summative e-assessment was introduced to a module. The impact this had on student engagement was measured by studying student activity within the module virtual learning environment (VLE). It was found that introduction of the e-assessments led to a significant increase in VLE activity compared to the VLE activity in that module the previous year, and also compared to the VLE activity of two other modules studied by the same student cohort. As many institutions move towards greater blended or online deliveries it will become more important to ensure that VLEs encourage high levels of student engagement in order to maintain or enhance the student experience. Keywords : continuous assessment, learning analytics, student engagement, virtual learning environment

MYCN Silencing by RNA Interference Induces Neurogenesis and Suppresses Proliferation in Models of Neuroblastoma with Resistance to Retinoic Acid

Neuroblastoma (NB) is the most common solid tumor in childhood. Twenty percent of patients display MYCN amplification, which indicates a very poor prognosis. MYCN is a highly specific target for an NB tumor therapy as MYCN expression is absent or very low in most normal cells, while, as a transcription factor, it regulates many essential cell activities in tumor cells. We aim to develop a therapy for NB based on MYCN silencing by short interfering RNA (siRNA) molecules, which can silence target genes by RNA interference (RNAi), a naturally occurring method of gene silencing. It has been shown previously that MYCN silencing can induce apoptosis and differentiation in MYCN amplified NB. In this article, we have demonstrated that siRNA-mediated silencing of MYCN in MYCN-amplified NB cells induced neurogenesis in NB cells, whereas retinoic acid (RA) treatment did not. RA can differentiate NB cells and is used for treatment of residual disease after surgery or chemotherapy, but resistance can develop. In addition, MYCN siRNA treatment suppressed growth in a MYCN-amplified NB cell line more than that by RA. Our result suggests that gene therapy using RNAi targeting MYCN can be a novel therapy toward MYCN-amplified NB that have complete or partial resistance toward RA

Filamin-A Regulates Neutrophil Uropod Retraction through RhoA during Chemotaxis

Filamin-A (FLNa) has been shown to be a key cross-linker of actin filaments in the leading edge of a motile melanoma cell line, however its role in neutrophils undergoing chemotaxis is unknown. Using a murine transgenic model in which FLNa is selectively deleted in granulocytes, we report that, while neutrophils lacking FLNa show normal polarization and pseudopod extension, they exhibit obvious defects in uropod retraction. This uropod retraction defect was found to be a direct result of reduced FLNa mediated activation of the small GTPase RhoA and myosin mediated actin contraction in the FLNa null cells. This results in a neutrophil recruitment defect in FLNa null mice. The compensatory increase in FLNb levels that was observed in the FLNa null neutrophils may be sufficient to compensate for the lack of FLNa at the leading edge allowing for normal polarization, however this compensation is unable to regulate RhoA activated tail retraction at the rear of the cell

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

The developmental regulator Pax6 is essential for maintenance of islet cell function in the adult mouse pancreas

The transcription factor Pax6 is a developmental regulator with a crucial role in development of the eye, brain, and olfactory system. Pax6 is also required for correct development of the endocrine pancreas and specification of hormone producing endocrine cell types. Glucagon-producing cells are almost completely lost in Pax6-null embryos, and insulin-expressing beta and somatostatin-expressing delta cells are reduced. While the developmental role of Pax6 is well-established, investigation of a further role for Pax6 in the maintenance of adult pancreatic function is normally precluded due to neonatal lethality of Pax6-null mice. Here a tamoxifen-inducible ubiquitous Cre transgene was used to inactivate Pax6 at 6 months of age in a conditional mouse model to assess the effect of losing Pax6 function in adulthood. The effect on glucose homeostasis and the expression of key islet cell markers was measured. Homozygous Pax6 deletion mice, but not controls, presented with all the symptoms of classical diabetes leading to severe weight loss requiring termination of the experiment five weeks after first tamoxifen administration. Immunohistochemical analysis of the pancreata revealed almost complete loss of Pax6 and much reduced expression of insulin, glucagon, and somatostatin. Several other markers of islet cell function were also affected. Notably, strong upregulation in the number of ghrelin-expressing endocrine cells was observed. These findings demonstrate that Pax6 is essential for adult maintenance of glucose homeostasis and function of the endocrine pancreas

Cross-Sectional Surveys of the Prevalence of Follicular Trachoma and Trichiasis in The Gambia: Has Elimination Been Reached?

BACKGROUND: The Gambia's National Eye Health Programme has made a concerted effort to reduce the prevalence of trachoma. The present study had two objectives. The first was to conduct surveillance following mass drug administrations to determine whether The Gambia has reached the World Health Organization's (WHO) criteria for trachoma elimination, namely a prevalence of trachomatous inflammation-follicular (TF) of less than 5% in children aged 1 to 9 years. The second was to determine the prevalence of trichiasis (TT) cases unknown to the programme and evaluate whether these meet the WHO criteria of less than 0.1% in the total population. METHODOLOGY/PRINCIPAL FINDINGS: Three cross-sectional surveys were conducted between 2011 and 2013 to determine the prevalence of TF and TT in each of nine surveillance zones. Each zone was of similar size, with a population of 60,000 to 90,000, once urban settlements were excluded. Trachoma grading was carried out according to the WHO's simplified trachoma grading system. The prevalence of TF in children aged 1 to 9 years was less than 5% in each surveillance zone at each of the three surveys. The prevalence of TT cases varied by zone from 0 to 1.7% of adults greater than 14 years while the prevalence of TT cases unknown to the country's National Eye Health Programme was estimated at 0.15% total population. CONCLUSIONS/SIGNIFICANCE: The Gambia has reached the elimination threshold for TF in children. Further work is needed to bring the number of unknown TT cases below the elimination threshold

Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin is a corner-stone of trachoma control however it may drive the emergence of antimicrobial resistance. In a cluster-randomized trial (Clinical trial gov NCT00792922), we compared the reduction in the prevalence of active trachoma in communities that received three annual rounds of MDA to that in communities that received a single treatment round. We used the framework of this trial to carry out an opportunistic study to investigate if the increased rounds of treatment resulted in increased prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus. Three cross-sectional surveys were conducted in two villages receiving three annual rounds of MDA (3 × treatment arm). Surveys were conducted immediately before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. The final survey also included six villages that had received only one round of MDA 30 months previously (1 × treatment arm). RESULTS: In the 3 × treatment arm, a short-term increase in prevalence of S. aureus carriage was seen following MDA from 24.6% at CSS-1 to 38.6% at CSS-2 (p < 0.001). Prevalence fell to 8.8% at CSS-3 (p < 0.001). A transient increase was also seen in prevalence of carriage of azithromycin resistant (Azm(R)) strains from 8.9% at CSS-1 to 34.1% (p < 0.001) in CSS-2 and down to 7.3% (p = 0.417) in CSS-3. A similar trend was observed for prevalence of carriage of macrolide-inducible-clindamycin resistant (iMLSB) strains. In CSS-3, prevalence of carriage of resistant strains was higher in the 3 × treatment arm than in the 1 × treatment (Azm(R) 7.3% vs. 1.6%, p = 0.010; iMLSB 5.8% vs. 0.8%, p < 0.001). Macrolide resistance was attributed to the presence of msr and erm genes. CONCLUSIONS: Three annual rounds of MDA with azithromycin were associated with a short-term increase in both the prevalence of nasopharyngeal carriage of S. aureus and prevalence of carriage of Azm(R) and iMLSB S. aureus. TRIAL REGISTRATION: This study was ancillary to the Partnership for the Rapid Elimination of Trachoma, ClinicalTrials.gov NCT00792922 , registration date November 17, 2008

Effects of ecosystem protection on scallop populations within a community-led temperate marine reserve

This study investigated the effects of a newly established, fully protected marine reserve on benthic habitats and two commercially valuable species of scallop in Lamlash Bay, Isle of Arran, United Kingdom. Annual dive surveys from 2010 to 2013 showed the abundance of juvenile scallops to be significantly greater within the marine reserve than outside. Generalised linear models revealed this trend to be significantly related to the greater presence of macroalgae and hydroids growing within the boundaries of the reserve. These results suggest that structurally complex habitats growing within the reserve have substantially increased spat settlement and/or survival. The density of adult king scallops declined threefold with increasing distance from the boundaries of the reserve, indicating possible evidence of spillover or reduced fishing effort directly outside and around the marine reserve. However, there was no difference in the mean density of adult scallops between the reserve and outside. Finally, the mean age, size, and reproductive and exploitable biomass of king scallops were all significantly greater within the reserve. In contrast to king scallops, the population dynamics of queen scallops (Aequipecten opercularis) fluctuated randomly over the survey period and showed little difference between the reserve and outside. Overall, this study is consistent with the hypothesis that marine reserves can encourage the recovery of seafloor habitats, which, in turn, can benefit populations of commercially exploited species, emphasising the importance of marine reserves in the ecosystem-based management of fisheries

The lived experiences of experienced Vipassana Mahasi meditators: an interpretative phenomenological analysis.

Research into the effects and mechanisms of mindfulness training draws predominantly on quantitative research. There is a lack of understanding about the subjective experiences of experienced mindfulness meditators, which may provide additional insights into the effects, processes and context of mindfulness training. This qualitative study explored the lived experiences of a novel group of experienced mindfulness meditators who practise Vipassana Mahasi (VM) meditation. The study aimed to understand how experienced VM practitioners make sense of the effects of practice and what processes they ascribe to it. Participants attended semistructured interviews, and their responses were analysed using interpretative phenomenological analysis. Results yielded overarching themes including (a) improvements in hedonic and eudaimonic well-being; (b) insights into self, others and perception of reality; (c) attaining equanimity; and (d) physical and interpersonal difficulties. Participants perceived VM as a ‘cleansing’ process whereby maladaptive responses were eliminated through mindfulness, other supportive mental qualities, decentering and nonattachment. The findings revealed a complex and dynamic set of interdependent outcomes and processes, which are reinforced by Buddhist teachings and ethical practices. This study highlights the need for additional interdisciplinary research into topics such as insight generation and supportive mental qualities cultivated during VM, novel states of well-being informed by Buddhist constructs and interpersonal difficulties related to long-term practice. Findings also suggest that incorporating Buddhist teachings and ethics into mindfulness-based interventions may enhance practitioner understanding and implementation of meditation techniques.N/