The Diabetes Manual trial protocol – a cluster randomized controlled trial of a self-management intervention for type 2 diabetes [ISRCTN06315411]

Background The Diabetes Manual is a type 2 diabetes self-management programme based upon the clinically effective 'Heart Manual'. The 12 week programme is a complex intervention theoretically underpinned by self-efficacy theory. It is a one to one intervention meeting United Kingdom requirements for structured diabetes-education and is delivered within routine primary care. Methods/design In a two-group cluster randomized controlled trial, GP practices are allocated by computer minimisation to an intervention group or a six-month deferred intervention group. We aim to recruit 250 participants from 50 practices across central England. Eligibility criteria are adults able to undertake the programme with type 2 diabetes, not taking insulin, with HbA1c over 8% (first 12 months) and following an agreed protocol change over 7% (months 13 to 18). Following randomisation, intervention nurses receive two-day training and delivered the Diabetes Manual programme to participants. Deferred intervention nurses receive the training following six-month follow-up. Primary outcome is HbA1c with total and HDL cholesterol; blood pressure, body mass index; self-efficacy and quality of life as additional outcomes. Primary analysis is between-group HbA1c differences at 6 months powered to give 80% power to detect a difference in HbA1c of 0.6%. A 12 month cohort analysis will assess maintenance of effect and assess relationship between self-efficacy and outcomes, and a qualitative study is running alongside. Discussion This trial incorporates educational and psychological diabetes interventions into a single programme and assesses both clinical and psychosocial outcomes. The trial will increase our understanding of intervention transferability between conditions, those diabetes related health behaviours that are more or less susceptible to change through efficacy enhancing mechanisms and how this impacts on clinical outcomes

Soundness and completeness proofs by coinductive methods

We show how codatatypes can be employed to produce compact, high-level proofs of key results in logic: the soundness and completeness of proof systems for variations of first-order logic. For the classical completeness result, we first establish an abstract property of possibly infinite derivation trees. The abstract proof can be instantiated for a wide range of Gentzen and tableau systems for various flavors of first-order logic. Soundness becomes interesting as soon as one allows infinite proofs of first-order formulas. This forms the subject of several cyclic proof systems for first-order logic augmented with inductive predicate definitions studied in the literature. All the discussed results are formalized using Isabelle/HOL’s recently introduced support for codatatypes and corecursion. The development illustrates some unique features of Isabelle/HOL’s new coinductive specification language such as nesting through non-free types and mixed recursion–corecursion

High-density information storage in an absolutely defined aperiodic sequence of monodisperse copolyester

Synthesis of a polymer composed of a large discrete number of chemically distinct monomers in an absolutely defined aperiodic sequence remains a challenge in polymer chemistry. The synthesis has largely been limited to oligomers having a limited number of repeating units due to the difficulties associated with the step-by-step addition of individual monomers to achieve high molecular weights. Here we report the copolymers of ??-hydroxy acids, poly(phenyllactic-co-lactic acid) (PcL) built via the cross-convergent method from four dyads of monomers as constituent units. Our proposed method allows scalable synthesis of sequence-defined PcL in a minimal number of coupling steps from reagents in stoichiometric amounts. Digital information can be stored in an aperiodic sequence of PcL, which can be fully retrieved as binary code by mass spectrometry sequencing. The information storage density (bit/Da) of PcL is 50% higher than DNA, and the storage capacity of PcL can also be increased by adjusting the molecular weight (~38???kDa)

Magnetic Coupling in the Quiet Solar Atmosphere

Three kinds of magnetic couplings in the quiet solar atmosphere are highlighted and discussed, all fundamentally connected to the Lorentz force. First the coupling of the convecting and overshooting fluid in the surface layers of the Sun with the magnetic field. Here, the plasma motion provides the dominant force, which shapes the magnetic field and drives the surface dynamo. Progress in the understanding of the horizontal magnetic field is summarized and discussed. Second, the coupling between acoustic waves and the magnetic field, in particular the phenomenon of wave conversion and wave refraction. It is described how measurements of wave travel times in the atmosphere can provide information about the topography of the wave conversion zone, i.e., the surface of equal Alfv\'en and sound speed. In quiet regions, this surface separates a highly dynamic magnetic field with fast moving magnetosonic waves and shocks around and above it from the more slowly evolving field of high-beta plasma below it. Third, the magnetic field also couples to the radiation field, which leads to radiative flux channeling and increased anisotropy in the radiation field. It is shown how faculae can be understood in terms of this effect. The article starts with an introduction to the magnetic field of the quiet Sun in the light of new results from the Hinode space observatory and with a brief survey of measurements of the turbulent magnetic field with the help of the Hanle effect.Comment: To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Prioritizing micronutrients for the purpose of reviewing their requirements: a protocol developed by EURRECA

Background: The EURRECA (EURopean micronutrient RECommendations Aligned) Network of Excellence (http://www.eurreca.org) is working towards the development of aligned recommendations. A protocol was required to assign resources to those micronutrients for which recommendations are most in need of alignment. Methods: Three important 'a priori' criteria were the basis for ranking micronutrients: (A) the amount of new scientific evidence, particularly from randomized controlled trials; (B) the public health relevance of micronutrients; (C) variations in current micronutrient recommendations. A total of 28 micronutrients were included in the protocol, which was initially undertaken centrally by one person for each of the different population groups defined in EURRECA: infants, children and adolescents, adults, elderly, pregnant and lactating women, and low income and immigrant populations. The results were then reviewed and refined by EURRECA's population group experts. The rankings of the different population groups were combined to give an overall average ranking of micronutrients. Results: The 10 highest ranked micronutrients were vitamin D, iron, folate, vitamin B12, zinc, calcium, vitamin C, selenium, iodine and copper. Conclusions: Micronutrient recommendations should be regularly updated to reflect new scientific nutrition and public health evidence. The strategy of priority setting described in this paper will be a helpful procedure for policy makers and scientific advisory bodies. European Journal of Clinical Nutrition (2010) 64, S19-530; doi:10.1038/ejcn.2010.5

Natriuretic peptide vs. clinical information for diagnosis of left ventricular systolic dysfunction in primary care

<p>Abstract</p> <p>Background</p> <p>Screening of primary care patients at risk for left ventricular systolic dysfunction by a simple blood-test might reduce referral rates for echocardiography. Whether or not natriuretic peptide testing is a useful and cost-effective diagnostic instrument in primary care settings, however, is still a matter of debate.</p> <p>Methods</p> <p>N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, clinical information, and echocardiographic data of left ventricular systolic function were collected in 542 family practice patients with at least one cardiovascular risk factor. We determined the diagnostic power of the NT-proBNP assessment in ruling out left ventricular systolic dysfunction and compared it to a risk score derived from a logistic regression model of easily acquired clinical information.</p> <p>Results</p> <p>23 of 542 patients showed left ventricular systolic dysfunction. Both NT-proBNP and the clinical risk score consisting of dyspnea at exertion and ankle swelling, coronary artery disease and diuretic treatment showed excellent diagnostic power for ruling out left ventricular systolic dysfunction. AUC of NT-proBNP was 0.83 (95% CI, 0.75 to 0.92) with a sensitivity of 0.91 (95% CI, 0.71 to 0.98) and a specificity of 0.46 (95% CI, 0.41 to 0.50). AUC of the clinical risk score was 0.85 (95% CI, 0.79 to 0.91) with a sensitivity of 0.91 (95% CI, 0.71 to 0.98) and a specificity of 0.64 (95% CI, 0.59 to 0.67). 148 misclassifications using NT-proBNP and 55 using the clinical risk score revealed a significant difference (McNemar test; p < 0.001) that was based on the higher specificity of the clinical risk score.</p> <p>Conclusion</p> <p>The evaluation of clinical information is at least as effective as NT-proBNP testing in ruling out left ventricular systolic dysfunction in family practice patients at risk. If these results are confirmed in larger cohorts and in different samples, family physicians should be encouraged to rely on the diagnostic power of the clinical information from their patients.</p

Mechanisms of Intragastric pH Sensing

Luminal amino acids and lack of luminal acidity as a result of acid neutralization by intragastric foodstuffs are powerful signals for acid secretion. Although the hormonal and neural pathways underlying this regulatory mechanism are well understood, the nature of the gastric luminal pH sensor has been enigmatic. In clinical studies, high pH, tryptic peptides, and luminal divalent metals (Ca2+ and Mg2+) increase gastrin release and acid production. The calcium-sensing receptor (CaSR), first described in the parathyroid gland but expressed on gastric G cells, is a logical candidate for the gastric acid sensor. Because CaSR ligands include amino acids and divalent metals, and because extracellular pH affects ligand binding in the pH range of the gastric content, its pH, metal, and nutrient-sensing functions are consistent with physiologic observations. The CaSR is thus an attractive candidate for the gastric luminal sensor that is part of the neuroendocrine negative regulatory loop for acid secretion

Knowledge networks and universities : locational and organisational aspects of knowledge transfer interactions

This paper explores the nature of the significant knowledge networks universities form with external organisations through knowledge transfer activities. Focussing on the UK higher education system, the analysis focuses on examining the extent to which organisational and locational characteristics are associated with the nature of these networks, finding that the nature of the networks universities form through knowledge transfer are related to both characteristics. In particular, we find that the institution’s status is important with more established universities are likely to have a more diverse range of organisations with which they interact, as well as a higher number of non-local interactions. In terms of geographic location, we find that universities within lagging regions tend to have more locally focused networks than universities in more leading regions. Overall, the knowledge transfer networking capacity of universities is found to be associated with the regional business environment within which they are situated, with the results going someway to confirming the importance of the role of universities in regional innovation systems, However, it also the case that more established, research focussed, universities are more likely to form part of wider , and possibly even more globalised, knowledge networks. Therefore, both the flow and stock of knowledge within regions is likely to be influenced by the networks formed by its universities, which has implications for both regional innovation capability and regional competitiveness

Psychosis Endophenotypes:A Gene-Set-Specific Polygenic Risk Score Analysis

Background and Hypothesis:Endophenotypes can help to bridge the gap between psychosis and its genetic predispositions, but their underlying mechanisms remain largely unknown. This study aims to identify biological mechanisms that are relevant to the endophenotypes for psychosis, by partitioning polygenic risk scores into specific gene sets and testing their associations with endophenotypes.Study Design:We computed polygenic risk scores for schizophrenia and bipolar disorder restricted to brain-related gene sets retrieved from public databases and previous publications. Three hundred and seventy-eight gene-set-specific polygenic risk scores were generated for 4506 participants. Seven endophenotypes were also measured in the sample. Linear mixed-effects models were fitted to test associations between each endophenotype and each gene-set-specific polygenic risk score.Study Results:After correction for multiple testing, we found that a reduced P300 amplitude was associated with a higher schizophrenia polygenic risk score of the forebrain regionalization gene set (mean difference per SD increase in the polygenic risk score: −1.15 µV; 95% CI: −1.70 to −0.59 µV; P = 6 × 10−5). The schizophrenia polygenic risk score of forebrain regionalization also explained more variance of the P300 amplitude (R2 = 0.032) than other polygenic risk scores, including the genome-wide polygenic risk scores.Conclusions:Our finding on reduced P300 amplitudes suggests that certain genetic variants alter early brain development thereby increasing schizophrenia risk years later. Gene-set-specific polygenic risk scores are a useful tool to elucidate biological mechanisms of psychosis and endophenotypes, offering leads for experimental validation in cellular and animal models

Prevalence of Symptomatic Heart Failure with Reduced and with Normal Ejection Fraction in an Elderly General Population-The CARLA Study

Background/Objectives: Chronic heart failure (CHF) is one of the most important public health concerns in the industrialized world having increasing incidence and prevalence. Although there are several studies describing the prevalence of heart failure with reduced ejection fraction (HFREF) and heart failure with normal ejection fraction (HFNEF) in selected populations, there are few data regarding the prevalence and the determinants of symptomatic heart failure in the general population. Methods: Cross-sectional data of a population-based German sample (1,779 subjects aged 45-83 years) were analyzed to determine the prevalence and determinants of chronic SHF and HFNEF defined according to the European Society of Cardiology using symptoms, echocardiography and serum NT-proBNP. Prevalence was age-standardized to the German population as of December 31st, 2005. Results: The overall age-standardized prevalence of symptomatic CHF was 7.7% (95%CI 6.0-9.8) for men and 9.0% (95%CI 7.0-11.5) for women. The prevalence of CHF strongly increased with age from 3.0% among 45-54- year-old subjects to 22.0% among 75-83- year-old subjects. Symptomatic HFREF could be shown in 48% (n = 78), symptomatic HFNEF in 52% (n = 85) of subjects with CHF. The age-standardized prevalence of HFREF was 3.8 % (95%CI 2.4-5.8) for women and 4.6 % (95%CI 3.6-6.3) for men. The age-standardized prevalence of HFNEF for women and men was 5.1 % (95%CI 3.8-7.0) and 3.0 % (95%CI 2.1-4.5), respectively. Persons with CHF were more likely to have hypertension (PR = 3.4; 95%CI 1.6-7.3) or to have had a previous myocardial infarction (PR = 2.5, 95%CI 1.8-3.5). Conclusion: The prevalence of symptomatic CHF appears high in this population compared with other studies. While more women were affected by HFNEF than men, more male subjects suffered from HFREF. The high prevalence of symptomatic CHF seems likely to be mainly due to the high prevalence of cardiovascular risk factors in this population