Correlation between measures of insulin resistance in fasting and non-fasting blood

<p>Abstract</p> <p>Background</p> <p>Epidemiological investigation of insulin resistance is difficult. Standard measures of insulin resistance require invasive investigations, which are impractical for large-scale studies. Surrogate measures using fasting blood samples have been developed, but even these are difficult to obtain in population-based studies. Measures of insulin resistance have not been validated in non-fasting blood samples. Our objective was to assess the correlations between fasting and non-fasting measures of insulin resistance/sensitivity.</p> <p>Methods</p> <p>Fasting and non-fasting measurements of metabolic function were compared in 30 volunteers (15 male) aged 28 to 48 years. Participants provided a morning blood sample after an overnight fast and a second sample approximately 4 hours after lunch on the same day.</p> <p>Results</p> <p>Non-fasting levels of the adipokines leptin, adiponectin, and leptin:adiponectin ratios were not significantly different and highly correlated with fasting values (r values 0.95, 0.96, and 0.95 respectively, P values < 0.001). There were moderate correlations between fasting and non-fasting estimates of insulin sensitivity using the McAuley (r = 0.60, P = 0.001) and QUICKI formulae (r = 0.39, P = 0.037). The HOMA-IR estimate of insulin resistance was also moderately correlated (r = 0.45, P = 0.016).</p> <p>Conclusions</p> <p>Semi-fasting measures of leptin, adiponectin, and leptin:adiponectin ratios correlate closely with fasting values and are likely to be sufficient for population-based research. Other measures of insulin resistance or sensitivity in semi-fasted blood samples are moderately correlated with values obtained after an overnight fast. These estimates of insulin resistance/sensitivity may also be adequate for many epidemiological studies and would avoid the difficulties of obtaining fasting blood samples.</p

Contrasting the Percutaneous Nerve Evaluation Versus Staged Implantation in Sacral Neuromodulation

Sacral neuromodulation is increasingly used for the treatment of voiding dysfunction, pelvic pain syndromes, and gastrointestinal disorders. While increased use of this technology has led to a greater understanding of its potential as well as its limitations, difficulty persists in identifying the patients that will benefit most. Either of two trial stimulation techniques is performed before placement of a permanent neuromodulator: the monopolar percutaneous nerve evaluation and the tined quadripolar staged trial. The preponderance of recent literature asserts the superior sensitivity of the staged trial over percutaneous nerve evaluation. However, the techniques offer disparate advantages, and other issues, such as cost-effectiveness, remain largely unexplored. The role of sacral neuromodulation will continue to expand as physicians and patients become increasingly aware of its therapeutic potential. Widespread adoption of this clinically superior technique will most rapidly help the greatest number of patients

Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security

Studies on the clinical significance of nonesterified and total cholesterol in urine

Gas-liquid chromatographic determinations of nonesterified and total urinary cholesterol were performed in 137 normals, 264 patients with various internal diseases without evidence of neoplasias or diseases of the kidney or urinary tract, 497 patients with malignancies and 236 patients with diseases of the kidney, urinary tract infections or prostatic adenoma with residual urine. A normal range (mean±2 SD) of 0.2–2.2 mg/24 hours nonesterified cholesterol (NEC) and of 0.3–3.0 mg/24 hours total cholesterol (TC) was calculated. Values of urinary cholesterol excretion were independent of age and sex and did not correlate with cholesterol levels in plasma. Patients with various internal diseases, without evidence of neoplasias nor diseases of the kidney or obstruction of the urinary tract, showed normal urinary cholesterol excretions, as did patients with infections of the urinary tract. However, elevated urinary cholesterol was found in patients with diseases of the kidney or urinary tract obstruction (prostatic adenoma with residual urine), malignant diseases of the urogenital tract and metastasing carcinoma of the breast. In patients with other malignant diseases urinary cholesterol was usually normal. Lesions of the urothelial cell membranes are considered to be the most likely cause of urinary cholesterol hyperexcretion. The clinical value of urinary cholesterol determinations as a possible screening test for urogenital carcinomas in unselected populations is limited by lacking specificity, expensive methodology and low prevalence of the mentioned carcinomas, although elevated urinary cholesterol excretions have been observed in early clinical stages of urogenital cancers

Individualization as driving force of clustering phenomena in humans

One of the most intriguing dynamics in biological systems is the emergence of clustering, the self-organization into separated agglomerations of individuals. Several theories have been developed to explain clustering in, for instance, multi-cellular organisms, ant colonies, bee hives, flocks of birds, schools of fish, and animal herds. A persistent puzzle, however, is clustering of opinions in human populations. The puzzle is particularly pressing if opinions vary continuously, such as the degree to which citizens are in favor of or against a vaccination program. Existing opinion formation models suggest that "monoculture" is unavoidable in the long run, unless subsets of the population are perfectly separated from each other. Yet, social diversity is a robust empirical phenomenon, although perfect separation is hardly possible in an increasingly connected world. Considering randomness did not overcome the theoretical shortcomings so far. Small perturbations of individual opinions trigger social influence cascades that inevitably lead to monoculture, while larger noise disrupts opinion clusters and results in rampant individualism without any social structure. Our solution of the puzzle builds on recent empirical research, combining the integrative tendencies of social influence with the disintegrative effects of individualization. A key element of the new computational model is an adaptive kind of noise. We conduct simulation experiments to demonstrate that with this kind of noise, a third phase besides individualism and monoculture becomes possible, characterized by the formation of metastable clusters with diversity between and consensus within clusters. When clusters are small, individualization tendencies are too weak to prohibit a fusion of clusters. When clusters grow too large, however, individualization increases in strength, which promotes their splitting.Comment: 12 pages, 4 figure

A randomized trial to monitor the efficacy and effectiveness by QT-NASBA of artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment and transmission control of uncomplicated Plasmodium falciparum malaria in western Kenya

<p>Abstract</p> <p>Background</p> <p>Many countries have implemented artemisinin-based combination therapy (ACT) for the first-line treatment of malaria. Although many studies have been performed on efficacy and tolerability of the combination arthemeter-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP), less is known of the effect of these drugs on gametocyte development, which is an important issue in malaria control.</p> <p>Methods and results</p> <p>In this two-arm randomized controlled trial, 146 children were treated with either AL or DP. Both groups received directly observed therapy and were followed for 28 days after treatment. Blood samples were analysed with microscopy and NASBA. In comparison with microscopy NASBA detected much more gametocyte positive individuals. Moreover, NASBA showed a significant difference in gametocyte clearance in favour of AL compared to DP. The decline of parasitaemia was slower and persistence or development of gametocytes was significantly higher and longer at day 3, 7 and 14 in the DP group but after 28 days no difference could be observed between both treatment arms.</p> <p>Conclusion</p> <p>Although practical considerations could favour the use of one drug over another, the effect on gametocytogenesis should also be taken into account and studied further using molecular tools like NASBA. This also applies when a new drug is introduced.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN36463274</p

Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy

Next-generation radio surveys are about to transform radio astronomy by discovering and studying tens of millions of previously unknown radio sources. These surveys will provide new insights to understand the evolution of galaxies, measuring the evolution of the cosmic star formation rate, and rivalling traditional techniques in the measurement of fundamental cosmological parameters. By observing a new volume of observational parameter space, they are also likely to discover unexpected new phenomena. This review traces the evolution of extragalactic radio continuum surveys from the earliest days of radio astronomy to the present, and identifies the challenges that must be overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201

A systematic review of the use of financial incentives and penalties to encourage uptake of healthy behaviors: protocol

<p>Abstract</p> <p>Background</p> <p>The use of financial incentives and penalties to encourage uptake of healthy behaviors is increasingly seen as a viable intervention in developed countries. Previous reviews of the effectiveness of financial incentives and penalties for encouraging the uptake of healthy behaviors have focused on individual behaviors making it difficult to draw overall conclusions about the effectiveness of such interventions. This systematic review will explore the effectiveness of financial incentives and penalties for encouraging a wide range of behaviors, including: smoking cessation, increased physical activity, healthier dietary intake, sensible patterns of alcohol consumption, safe sun, safe sex, and primary preventive clinical behaviors.</p> <p>Methods</p> <p>Systematic methods will be used to search existing literature and screen studies for inclusion. All studies that meet the following inclusion criteria will be included in the review: participants were 18 years old or older and living in high-income countries; interventions included cash or cash-like incentives to promote the uptake of healthy behaviors, or cash or cash-like penalties to discourage unhealthy behaviors; the comparator was usual care or no intervention; study design was randomized controlled trial, cluster randomized controlled trial, controlled before and after study, or interrupted time series analysis. Two reviewers will independently screen the publications to ensure they meet the inclusion criteria. Quality will be assessed by two researchers, working independently, using the Cochrane risk of bias tool. Meta-analysis will be conducted, if appropriate. Any studies identified as at ‘high risk of bias’ will be excluded from meta-analysis.</p> <p>Discussion</p> <p>This systematic review will provide policy-relevant recommendations for the use of financial incentives and penalties as a method of encouraging uptake of healthy behaviors.</p

Enumeration of Functional T-Cell Subsets by Fluorescence-Immunospot Defines Signatures of Pathogen Burden in Tuberculosis

IFN-γ and IL-2 cytokine-profiles define three functional T-cell subsets which may correlate with pathogen load in chronic intracellular infections. We therefore investigated the feasibility of the immunospot platform to rapidly enumerate T-cell subsets by single-cell IFN-γ/IL-2 cytokine-profiling and establish whether immunospot-based T-cell signatures distinguish different clinical stages of human tuberculosis infection.We used fluorophore-labelled anti-IFN-γ and anti-IL-2 antibodies with digital overlay of spatially-mapped colour-filtered images to enumerate dual and single cytokine-secreting M. tuberculosis antigen-specific T-cells in tuberculosis patients and in latent tuberculosis infection (LTBI). We validated results against established measures of cytokine-secreting T-cells.Fluorescence-immunospot correlated closely with single-cytokine enzyme-linked-immunospot for IFN-γ-secreting T-cells and IL-2-secreting T-cells and flow-cytometry-based detection of dual IFN-γ/IL-2-secreting T-cells. The untreated tuberculosis signature was dominated by IFN-γ-only-secreting T-cells which shifted consistently in longitudinally-followed patients during treatment to a signature dominated by dual IFN-γ/IL-2-secreting T-cells in treated patients. The LTBI signature differed from active tuberculosis, with higher proportions of IL-2-only and IFN-γ/IL-2-secreting T-cells and lower proportions of IFN-γ-only-secreting T-cells.Fluorescence-immunospot is a quantitative, accurate measure of functional T-cell subsets; identification of cytokine-signatures of pathogen burden, distinct clinical stages of M. tuberculosis infection and long-term immune containment suggests application for treatment monitoring and vaccine evaluation

Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation

Background: Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity. Methods: Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis. Results: Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6–12 months post-IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI (AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72). Conclusions: Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations