Carbon monoxide induces cardiac arrhythmia via induction of the late Na+ current

Our data indicate that the proarrhythmic effects of CO arise from activation of NO synthase, leading to NO-mediated nitrosylation of Na(V)1.5 and to induction of the late Na(+) current. We also show that the antianginal drug ranolazine can abolish CO-induced early after-depolarizations, highlighting a novel approach to the treatment of CO-induced arrhythmias.

Towards a lawn without grass: the journey of the imperfect lawn and its analogues

In much of the English-speaking world the lawn is the most common of all garden features. For arguably a millennium it has played a significant role in the landscape and during that period it has been inextricably linked with grasses. Nevertheless other plant species have accompanied the grasses and also been used in creating lawns. From medieval wildflowers to Victorian weeds, the plants that challenge the formal concept of the perfect lawn have journeyed with it but have until recently remained only small players within the dominion of grass. By the beginning of the 21st century, with a new environmental ethos permeating the garden, the long journey of the grassy lawn and its plant companions has led to the grass monoculture being heretically rethought: by removing both the monoculture and the grass.

Content validation for level of use of feature rich systems: a Delphi study of electronic medical records systems

Introduction. Feature usage is a pre-requisite to realising the benefits of investments in feature rich systems. We propose that conceptualising the dependent variable 'system use' as 'level of use' and specifying it as a formative construct has greater value for measuring the post-adoption use of feature rich systems. We then validate the content of the construct as a first step in developing a research instrument to measure it. The context of our study is the post-adoption use of electronic medical records (EMR) by primary care physicians. Method. Initially, a literature review of the empirical context defines the scope based on prior studies. Having identified core features from the literature, they are further refined with the help of experts in a consensus seeking process that follows the Delphi technique. Results.The methodology was successfully applied to EMRs, which were selected as an example of feature rich systems. A review of EMR usage and regulatory standards provided the feature input for the first round of the Delphi process. A panel of experts then reached consensus after four rounds, identifying ten task-based features that would be indicators of level of use. Conclusions. To study why some users deploy more advanced features than others, theories of post-adoption require a rich formative dependent variable that measures level of use. We have demonstrated that a context sensitive literature review followed by refinement through a consensus seeking process is a suitable methodology to validate the content of this dependent variable. This is the first step of instrument development prior to statistical confirmation with a larger sample.

Sociodemographic determinants of diet quality of the EU elderly: a comparative analysis in four countries

Objective: To investigate the sociodemographic determinants of diet quality of the elderly in four EU countries. Design: Cross-sectional study. For each country, a regression was performed of a multidimensional index of dietary quality v. sociodemographic variables. Setting In Finland, Finnish Household Budget Survey (1998 and 2006); in Sweden, SNAC-K (2001–2004); in the UK, Expenditure & Food Survey (2006–07); in Italy, Multi-purpose Survey of Daily Life (2009). Subjects: One- and two-person households of over-50s (Finland, n 2994; UK, n 4749); over-50 s living alone or in two-person households (Italy, n 7564); over-60 s (Sweden, n 2023). Results: Diet quality among the EU elderly is both low on average and heterogeneous across individuals. The regression models explained a small but significant part of the observed heterogeneity in diet quality. Resource availability was associated with diet quality either negatively (Finland and UK) or in a non-linear or non-statistically significant manner (Italy and Sweden), as was the preference for food parameter. Education, not living alone and female gender were characteristics positively associated with diet quality with consistency across the four countries, unlike socio-professional status, age and seasonality. Regional differences within countries persisted even after controlling for the other sociodemographic variables. Conclusions: Poor dietary choices among the EU elderly were not caused by insufficient resources and informational measures could be successful in promoting healthy eating for healthy ageing. On the other hand, food habits appeared largely set in the latter part of life, with age and retirement having little influence on the healthiness of dietary choices.

Pooling of forecasts

We consider forecasting using a combination, when no model coincides with a non-constant data generation process (DGP). Practical experience suggests that combining forecasts adds value, and can even dominate the best individual device. We show why this can occur when forecasting models are differentially mis-specified, and is likely to occur when the DGP is subject to location shifts. Moreover, averaging may then dominate over estimated weights in the combination. Finally, it cannot be proved that only non-encompassed devices should be retained in the combination. Empirical and Monte Carlo illustrations confirm the analysis.

High density lipoprotein: guardian of the vascular system?

The role of low-density lipoprotein in the development of coronary heart disease (CHD) is well recognised. There is also growing evidence that high-density lipoprotein cholesterol (HDL-C) is a powerful inverse predictor for premature CHD and that maintaining a high HDL-C level may guard against atherosclerosis. Patients with low HDL-C levels often also have central obesity, insulin resistance and other features of the metabolic syndrome. This syndrome is both increasingly common and strongly implicated in the growing worldwide epidemic of type 2 diabetes. HDL-C may be increased by lifestyle changes, e.g. weight loss, physical activity and smoking cessation. Pharmacological agents such as fibrates, niacin and statins have also been shown significantly to elevate HDL-C. Although current guidelines are beginning to recognise the protective role of HDL-C level in preventing coronary events, HDL-C should be adopted soon as a target for intervention in its own right.

Inhibition of the cardiac Na+ channel Nav1.5 by carbon monoxide

Sub-lethal carbon monoxide (CO) exposure is frequently associated with myocardial arrhythmias and our recent studies have demonstrated that these may be attributable to modulation of cardiac Na+ channels, causing an increase in the late current and an inhibition of the peak current. Using a recombinant expression system, we demonstrate that CO inhibits peak human Nav1.5 current amplitude without activation of the late Na+ current observed in native tissue. Inhibition was associated with a hyperpolarizing shift in the steady-state inactivation properties of the channels and was unaffected by modification of channel gating induced by anemone toxin (rATX-II). Systematic pharmacological assessment indicated that no recognised CO-sensitive intracellular signalling pathways appeared to mediate CO inhibition of Nav1.5. Inhibition was, however, markedly suppressed by inhibition of nitric oxide (NO) formation, but NO donors did not mimic or occlude channel inhibition by CO, indicating that NO alone did not account for the actions of CO. Exposure of cells to dithiothreitol immediately before CO exposure also dramatically reduced the magnitude of current inhibition. Similarly, L-cysteine and N-ethylmaleimide significantly attenuated the inhibition caused by CO. In the presence of DTT and the NO inhibitor L-NAME, the ability of CO to inhibit Nav1.5 was almost fully prevented. Our data indicate that inhibition of peak Na+ current (which can lead to Brugada-syndrome like arrhythmias) occurs via a mechanism distinct from induction of the late current, requires NO formation and is dependent on channel redox state.

The mentoring of overseas trained teachers

Much research has been undertaken into the value of mentoring for beginning teachers. Less research has been done into the mentoring of Overseas Trained Teachers (OTTs). The studies that have been done suggest that mentors’ lack of cultural knowledge and of the pedagogical challenges faced by OTT-mentees may inhibit the integration of such teachers into school life. It may be that effective tailor-made training cannot be provided for OTTs by mentors whose skills or knowledge are insufficient. Lack of understanding of the cultural diversity of mentees may result, as studies show, in mentors failing to address relevant issues during the mentoring process. This study investigates the experiences of OTTs of mentorship in England, and suggests the importance of mentors having understanding of their culturally diverse OTT mentees. The implications of these findings in the context of recent teacher-training policy developments in England are discussed.

Genetical and comparative genomics of Brassica under altered Ca supply identifies Arabidopsis Ca-transporter orthologs

Although Ca transport in plants is highly complex, the overexpression of vacuolar Ca2+ transporters in crops is a promising new technology to improve dietary Ca supplies through biofortification. Here, we sought to identify novel targets for increasing plant Ca accumulation using genetical and comparative genomics. Expression quantitative trait locus (eQTL) mapping to 1895 cis- and 8015 trans-loci were identified in shoots of an inbred mapping population of Brassica rapa (IMB211 × R500); 23 cis- and 948 trans-eQTLs responded specifically to altered Ca supply. eQTLs were screened for functional significance using a large database of shoot Ca concentration phenotypes of Arabidopsis thaliana. From 31 Arabidopsis gene identifiers tagged to robust shoot Ca concentration phenotypes, 21 mapped to 27 B. rapa eQTLs, including orthologs of the Ca2+ transporters At-CAX1 and At-ACA8. Two of three independent missense mutants of BraA.cax1a, isolated previously by targeting induced local lesions in genomes, have allele-specific shoot Ca concentration phenotypes compared with their segregating wild types. BraA.CAX1a is a promising target for altering the Ca composition of Brassica, consistent with prior knowledge from Arabidopsis. We conclude that multiple-environment eQTL analysis of complex crop genomes combined with comparative genomics is a powerful technique for novel gene identification/prioritization.

The effect of light exposure on the degradation of latent fingerprints on brass surfaces: the use of silver electroless deposition as a visualization technique

We have studied the degradation of sebaceous fingerprints on brass surfaces using silver electroless deposition (SED) as a visualization technique. We have stored fingerprints on brass squares either (i) in a locked dark cupboard or (ii) in glass-filtered natural daylight for periods of 3 h, 24 h, 1 week, 3 weeks, and 6 weeks. We find that fingerprints on brass surfaces degrade much more rapidly when kept in the light than they do under dark conditions with a much higher proportion of high-quality prints found after 3 or 6 weeks of aging when stored in the dark. This process is more marked than for similar fingerprints on black PVC surfaces. Identifiable prints can be achieved on brass surfaces using both SED and cyanoacrylate fuming (CFM). SED is quick and straightforward to perform. CFM is more time-consuming but is versatile and can be applied to a wider range of metal surfaces than SED, for example brass surfaces which have been coated by a lacquer.

Association between sucrose intake and risk of overweight and obesity in a prospective sub-cohort of EPIC-Norfolk

Objective: The objective of this study was to investigate associations between sugar intake and overweight using dietary biomarkers in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). Design: Prospective cohort study Setting: European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) in the UK, recruitment between 1993 and 1997. Subjects: 1734 participants (39 – 77 years). Sucrose intake was assessed using 7-day diaries. Baseline spot urine samples were analysed for sucrose by GC-MS. Sucrose concentration adjusted by specific gravity was used as biomarker for intake. Regression analyses were used to investigate associations between sucrose intake and risk of BMI > 25 kg/m2 after three years of follow-up. Results: After three years of follow-up, mean BMI was 26.8 kg/m2. Self-reported sucrose intake was significantly positively associated with biomarker. Associations between biomarker and BMI were positive (β=0.25; 95% CI: 0.08; 0.43), while they were inverse when using self-reported dietary data (β=-1.40; 95% CI: -1.81; -0.99). Age- and sex-adjusted OR for BMI > 25 kg/m2 in participants in the fifth vs. first quintile was 1.54 (95% CI: 1.12; 2.12; pTrend=0.003,) when using biomarker and 0.56 (95% CI: 0.40; 0.77; pTrend<0.001) with self-reported dietary data. Conclusions: Our results suggest that sucrose measured by objective biomarker but not self-reported sucrose intake is positively associated with body mass index. Future studies should consider use of objective biomarkers of sucrose intake.

High prevalence of undernutrition and low dietary diversity in institutionalised elderly living in Sri Lanka

This research received no specific grant from any funding agency in the public, commercial and not-for-profit sectors. The authors wish to thank the participants, administrators and caregivers of the homes for elders for their enthusiastic cooperation and also the Nutrition Research Team of the Department of Applied Nutrition, Wayamba University of Sri Lanka, for their valuable assistance during the course of the study. The authors also wish to thank Mr. S. Rahanan for coordination and the assistance given in data collection especially in Tamil speaking participants. K.M.R designed and managed the study, interpreted the data and drafted the manuscript. M.P.P.M contributed to the data collection, data analysis and coordination of the study. M.W, K.G.J and J.A.L assisted in data interpretation and critical revision of the manuscript. The authors declare that there is no conflict of interest of any kind involved in this study or this publication. Ethical clearance for this study was obtained from the Ethical Review Committee of the Sri Lanka Medical Association (ERC/13-037).

Reforming theatre in Farnese Parma: the case of the Accademia degli Innominati (1574-1608)

The essay explores the socio-cultural role of the main academy in Parma, the Innominati (1574-1608), which flourished in the years when the Farnese dynasty was beginning to assert more forcefully its political control over the new state of Parma and Piacenza. The Innominati was from the start associated with the ruling dynasty, who must have recognized the importance of its cultural activities to strengthening their regime, particularly in the absence of a strong local university. This essay explores the institution’s contested position within the cultural landscape – as reflected also in its membership of courtiers, clergymen, and feudal aristocrats with more ambivalent relations with the Farnese. In particular, the focus falls on the theatrical activities of the group during the 1580s, a decade which saw the establishment of the Parma Index (1580) and the succession of the internationally celebrated Duke Alessandro Farnese (1587). Based on the little surviving evidence it is argued that the Academy in the 1580s became a creative hub for theatrical experimentation – through theoretical debate and composition, and possibly even performance. However, as relations between the Farnese and the local elites, especially feudal aristocrats, became more contested the Academy’s theatrical production and the public memory of this became increasingly controlled.

The practice of reading aloud in the high school: a preliminary investigation

The paper considers students’ views of why reading aloud takes place and what are its effects.The results of two small focus-group discussions are presented, in which high school students were given the opportunity to express their responses to the practice of reading aloud in the classroom. Their responses are considered in the context of theoretical perspectives: pedagogical, reader-response and social/vocational. Analysis of responses reveals acknowledgement that reading aloud is not only a useful skill but also that it is a site of anxiety and even conflict.