Objective: To compare different statistical methods for assessing the relative validity of a self-administered, 150-item, semi-quantitative food-frequency questionnaire (FFQ) with 4-day weighed diet records (WR). Design: Subjects completed the Scottish Collaborative Group FFQ and carried out a 4-day WR. Relative agreement between the FFQ and WR for energy-adjusted nutrient intakes was assessed by Pearson and Spearman rank correlation coefficients, the percentages of subjects classified into the same and opposite thirds of intake, and Cohen's weighted kappa. Subjects: Forty-one men, mean age 36 (range 21-56) years, and 40 women, mean age 33 (range 19-58) years, recruited from different locations in Aberdeen, Scotland. Results: Spearman correlation coefficients tended to be lower than Pearson correlation coefficients, and were above 0.5 for 10 of the 27 nutrients in men and 17 of the 27 nutrients in women. For nutrients with Spearman correlation coefficients above 0.5, the percentage of subjects correctly classified into thirds ranged from 39 to 78%, and weighted kappa values ranged from 0.23 to 0.66. Conclusions: Both Spearman correlation coefficients and weighted kappa values are useful in assessing the relative validity of estimates of nutrient intake by FFQs. Spearman correlation coefficients above 0.5, more than 50% of subjects correctly classified and less than 10% of subjects grossly misclassified into thirds, and weighted kappa values above 0.4 are recommended for nutrients of interest in epidemiological studies. Keywords Correlation coefficientsKappa statistic Food-frequency questionnaire Relative validity Weighed diet records Epidemiological methods Dietary assessmentThe semi-quantitative food-frequency questionnaire (FFQ) is the primary dietary assessment method used in epidemiological studies 1. Results from such studies can be interpreted with greater confidence if the questionnaire has a quantified validity; i.e. the ability of the questionnaire to measure what it is intended to measure. To assess the true validity of an FFQ would require measuring with high accuracy the usual self-selected diet of freeliving individuals over several months, which is not feasible. Therefore, researchers assess relative validity by comparing the FFQ with an alternative dietary assessment method with its own limitations.In epidemiological studies, the odds ratio or relative risk of disease in relation to nutrient intake is the most common measure of association presented. Consequently, FFQs must be able to rank individuals along the distribution of intake, so that individuals with low intakes can be separated from those with high intakes. Therefore, obtaining absolute nutrient intakes is not necessary. As long as FFQs can rank individuals, relative risk estimates will be accurate 2 . The usual method of assessing agreement in ranking between an FFQ and a reference method is to calculate Pearson correlation coefficients for log e -transformed data or Spearman rank correlation coefficients for data that are not n...

MicroRNAs (miRNAs) are small non-coding RNAs that function as negative gene expression regulators. Emerging evidence shows that, except for function in the cytoplasm, miRNAs are also present in the nucleus. However, the functional significance of nuclear miRNAs remains largely undetermined. By screening miRNA database, we have identified a subset of miRNA that functions as enhancer regulators. Here, we found a set of miRNAs show gene-activation function. We focused on miR-24-1 and found that this miRNA unconventionally activates gene transcription by targeting enhancers. Consistently, the activation was completely abolished when the enhancer sequence was deleted by TALEN. Furthermore, we found that miR-24-1 activates enhancer RNA (eRNA) expression, alters histone modification, and increases the enrichment of p300 and RNA Pol II at the enhancer locus. Our results demonstrate a novel mechanism of miRNA as an enhancer trigger.

Plants have a profound capacity to regenerate organs from differentiated somatic tissues, based on which propagating plants in vitro was made possible. Beside its use in biotechnology, in vitro shoot regeneration is also an important system to study de novo organogenesis. Phytohormones and transcription factor WUSCHEL (WUS) play critical roles in this process but whether and how epigenetic modifications are involved is unknown. Here, we report that epigenetic marks of DNA methylation and histone modifications regulate de novo shoot regeneration of Arabidopsis through modulating WUS expression and auxin signaling. First, functional loss of key epigenetic genes—including METHYLTRANSFERASE1 (MET1) encoding for DNA methyltransferase, KRYPTONITE (KYP) for the histone 3 lysine 9 (H3K9) methyltransferase, JMJ14 for the histone 3 lysine 4 (H3K4) demethylase, and HAC1 for the histone acetyltransferase—resulted in altered WUS expression and developmental rates of regenerated shoots in vitro. Second, we showed that regulatory regions of WUS were developmentally regulated by both DNA methylation and histone modifications through bisulfite sequencing and chromatin immunoprecipitation. Third, DNA methylation in the regulatory regions of WUS was lost in the met1 mutant, thus leading to increased WUS expression and its localization. Fourth, we did a genome-wide transcriptional analysis and found out that some of differentially expressed genes between wild type and met1 were involved in signal transduction of the phytohormone auxin. We verified that the increased expression of AUXIN RESPONSE FACTOR3 (ARF3) in met1 indeed was due to DNA demethylation, suggesting DNA methylation regulates de novo shoot regeneration by modulating auxin signaling. We propose that DNA methylation and histone modifications regulate de novo shoot regeneration by modulating WUS expression and auxin signaling. The study demonstrates that, although molecular components involved in organogenesis are divergently evolved in plants and animals, epigenetic modifications play an evolutionarily convergent role in this process.

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The components in plant signal transduction pathways are intertwined and affect each other to coordinate plant growth, development, and defenses to stresses. The role of ubiquitination in connecting these pathways, particularly plant innate immunity and flowering, is largely unknown. Here, we report the dual roles for the Arabidopsis (Arabidopsis thaliana) Plant U-box protein13 (PUB13) in defense and flowering time control. In vitro ubiquitination assays indicated that PUB13 is an active E3 ubiquitin ligase and that the intact U-box domain is required for the E3 ligase activity. Disruption of the PUB13 gene by T-DNA insertion results in spontaneous cell death, the accumulation of hydrogen peroxide and salicylic acid (SA), and elevated resistance to biotrophic pathogens but increased susceptibility to necrotrophic pathogens. The cell death, hydrogen peroxide accumulation, and resistance to necrotrophic pathogens in pub13 are enhanced when plants are pretreated with high humidity. Importantly, pub13 also shows early flowering under middle-and long-day conditions, in which the expression of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 and FLOWERING LOCUS T is induced while FLOWERING LOCUS C expression is suppressed. Finally, we found that two components involved in the SA-mediated signaling pathway, SID2 and PAD4, are required for the defense and flowering-time phenotypes caused by the loss of function of PUB13. Taken together, our data demonstrate that PUB13 acts as an important node connecting SA-dependent defense signaling and flowering time regulation in Arabidopsis.

In China, hypertension is common, and while recent studies suggest some improvements, more than half of affected individuals were unaware that they had hypertension. Rates of control remain low. National programs effective in preventing and controlling hypertension in China are urgently needed.

IntroductionIntravenous medication administration has traditionally been regarded as error prone, with high potential for harm. A recent US multisite study revealed few potentially harmful errors despite a high overall error rate. However, there is limited evidence about infusion practices in England and how they relate to prevalence and types of error.ObjectivesTo determine the prevalence, types and severity of errors and discrepancies in infusion administration in English hospitals, and to explore sources of variation, including the contribution of smart pumps.MethodsWe conducted an observational point prevalence study of intravenous infusions in 16 National Health Service hospital trusts. Observers compared each infusion against the medication order and local policy. Deviations were classified as errors or discrepancies based on their potential for patient harm. Contextual issues and reasons for deviations were explored qualitatively during observer debriefs.ResultsData were collected from 1326 patients and 2008 infusions. Errors were observed in 231 infusions (11.5%, 95% CI 10.2% to 13.0%). Discrepancies were observed in 1065 infusions (53.0%, 95% CI 50.8% to 55.2%). Twenty-three errors (1.1% of all infusions) were considered potentially harmful; none were judged likely to prolong hospital stay or result in long-term harm. Types and prevalence of errors and discrepancies varied widely among trusts, as did local policies. Deviations from medication orders and local policies were sometimes made for efficiency or patient need. Smart pumps, as currently implemented, had little effect, with similar error rates observed in infusions delivered with and without a smart pump (10.3% vs 10.8%, p=0.8).ConclusionErrors and discrepancies are relatively common in everyday infusion administrations but most have low potential for patient harm. Better understanding of performance variability to strategically manage risk may be a more helpful tactic than striving to eliminate all deviations.

BackgroundMedicines optimisation is a key role for hospital pharmacists, but with ever-increasing demands on services, there is a need to increase efficiency while maintaining patient safety.ObjectiveTo develop a prediction tool, the Medicines Optimisation Assessment Tool (MOAT), to target patients most in need of pharmacists’ input in hospital.MethodsPatients from adult medical wards at two UK hospitals were prospectively included into this cohort study. Data on medication-related problems (MRPs) were collected by pharmacists at the study sites as part of their routine daily clinical assessments. Data on potential risk factors, such as number of comorbidities and use of ‘high-risk’ medicines, were collected retrospectively. Multivariable logistic regression modelling was used to determine the relationship between risk factors and the study outcome: preventable MRPs that were at least moderate in severity. The model was internally validated and a simplified electronic scoring system developed.ResultsAmong 1503 eligible admissions, 610 (40.6%) experienced the study outcome. Eighteen risk factors were preselected for MOAT development, with 11 variables retained in the final model. The MOAT demonstrated fair predictive performance (concordance index 0.66) and good calibration. Two clinically relevant decision thresholds (ie, the minimum predicted risk probabilities to justify pharmacists’ input) were selected, with sensitivities of 90% and 66% (specificity 30% and 61%); these equate to positive predictive values of 47% and 54%, respectively. Decision curve analysis suggests that the MOAT has potential value in clinical practice in guiding decision-making.ConclusionThe MOAT has potential to predict those patients most at risk of moderate or severe preventable MRPs, experienced by 41% of admissions. External validation is now required to establish predictive accuracy in a new group of patients.