What guidance are researchers given on how to present network meta-analyses to end-users such as policymakers and clinicians? A systematic review

© 2014 Sullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: Network meta-analyses (NMAs) are complex methodological approaches that may be challenging for non-technical end-users, such as policymakers and clinicians, to understand. Consideration should be given to identifying optimal approaches to presenting NMAs that help clarify analyses. It is unclear what guidance researchers currently have on how to present and tailor NMAs to different end-users. Methods: A systematic review of NMA guidelines was conducted to identify guidance on how to present NMAs. Electronic databases and supplementary sources were searched for NMA guidelines. Presentation format details related to sample formats, target audiences, data sources, analysis methods and results were extracted and frequencies tabulated. Guideline quality was assessed following criteria developed for clinical practice guidelines. Results: Seven guidelines were included. Current guidelines focus on how to conduct NMAs but provide limited guidance to researchers on how to best present analyses to different end-users. None of the guidelines provided reporting templates. Few guidelines provided advice on tailoring presentations to different end-users, such as policymakers. Available guidance on presentation formats focused on evidence networks, characteristics of individual trials, comparisons between direct and indirect estimates and assumptions of heterogeneity and/or inconsistency. Some guidelines also provided examples of figures and tables that could be used to present information. Conclusions: Limited guidance exists for researchers on how best to present NMAs in an accessible format, especially for non-technical end-users such as policymakers and clinicians. NMA guidelines may require further integration with end-users' needs, when NMAs are used to support healthcare policy and practice decisions. Developing presentation formats that enhance understanding and accessibility of NMAs could also enhance the transparency and legitimacy of decisions informed by NMAs.The Canadian Institute of Health Research (CIHR) Drug Safety and Effectiveness Network (Funding reference number – 116573)

Record linkage research and informed consent: who consents?

BACKGROUND: Linking computerized health insurance records with routinely collected survey data is becoming increasingly popular in health services research. However, if consent is not universal, the requirement of written informed consent may introduce a number of research biases. The participants of a national health survey in Taiwan were asked to have their questionnaire results linked to their national health insurance records. This study compares those who consented with those who refused. METHODS: A national representative sample (n = 14,611 adults) of the general adult population aged 20 years or older who participated in the Taiwan National Health Interview Survey (NHIS) and who provided complete survey information were used in this study. At the end of the survey, the respondents were asked if they would give permission to access their National Health Insurance records. Information given by the interviewees in the survey was used to analyze who was more likely to consent to linkage and who wasn't. RESULTS: Of the 14,611 NHIS participants, 12,911 (88%) gave consent, and 1,700 (12%) denied consent. The elderly, the illiterate, those with a lower income, and the suburban area residents were significantly more likely to deny consent. The aborigines were significantly less likely to refuse. No discrepancy in gender and self-reported health was found between individuals who consented and those who refused. CONCLUSION: This study is the first population-based study in assessing the consent pattern in a general Asian population. Consistent with people in Western societies, in Taiwan, a typical Asian society, a high percentage of adults gave consent for their health insurance records and questionnaire results to be linked. Consenters differed significantly from non-consenters in important aspects such as age, ethnicity, and educational background. Consequently, having a high consent rate (88%) may not fully eliminate the possibility of selection bias. Researchers should take this source of bias into consideration in their study design and investigate any potential impact of this source of bias on their results

Simultaneous lateral and posterior ponticles resulting in the formation of a vertebral artery tunnel of the atlas: case report and review of the literature. Folia Neuropathol

Case report A b s t r a c t The foramen arcuale is infrequently found and is potentially a clinically/surgically significant anatomical variation of the atlas. When present, the vertebral artery travels through this bony ring after exiting the transverse foramen of the atlas and prior to entering the cranium. We present a case of an adult female skeleton noted to harbor both a foramen arcuale and a lateral ponticle that resulted in the formatio

Glucose in the hypothalamic paraventricular nucleus regulates GLP-1 release.

Glucokinase (GK) is highly expressed in the hypothalamic paraventricular nucleus (PVN); however, its role is currently unknown. We found that GK in the PVN acts as part of a glucose-sensing mechanism within the PVN that regulates glucose homeostasis by controlling glucagon-like peptide 1 (GLP-1) release. GLP-1 is released from enteroendocrine L cells in response to oral glucose. Here we identify a brain mechanism critical to the release of GLP-1 in response to oral glucose. We show that increasing expression of GK or injection of glucose into the PVN increases GLP-1 release in response to oral glucose. On the contrary, decreasing expression of GK or injection of nonmetabolizable glucose into the PVN prevents GLP-1 release. Our results demonstrate that gluco-sensitive GK neurons in the PVN are critical to the response to oral glucose and subsequent release of GLP-1

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript (19 pages, 5 figures) and supplementary information; added additional clarification on alternative adaptation models in supplementary informatio

Transmembrane but not soluble helices fold inside the ribosome tunnel

Integral membrane proteins are assembled into the ER membrane via a continuous ribosome-translocon channel. The hydrophobicity and thickness of the core of the membrane bilayer leads to the expectation that transmembrane (TM) segments minimize the cost of harbouring polar polypeptide backbones by adopting a regular pattern of hydrogen bonds to form α-helices before integration. Co-translational folding of nascent chains into an α-helical conformation in the ribosomal tunnel has been demonstrated previously, but the features governing this folding are not well understood. In particular, little is known about what features influence the propensity to acquire α-helical structure in the ribosome. Using in vitro translation of truncated nascent chains trapped within the ribosome tunnel and molecular dynamics simulations, we show that folding in the ribosome is attained for TM helices but not for soluble helices, presumably facilitating SRP (signal recognition particle) recognition and/or a favourable conformation for membrane integration upon translocon entry

Electroluminescent Characteristics of DBPPV–ZnO Nanocomposite Polymer Light Emitting Devices

We have demonstrated that fabrication and characterization of nanocomposite polymer light emitting devices with metal Zinc Oxide (ZnO) nanoparticles and 2,3-dibutoxy-1,4-poly(phenylenevinylene) (DBPPV). The current and luminance characteristics of devices with ZnO nanoparticles are much better than those of device with pure DBPPV. Optimized maximum luminance efficiencies of DBPPV–ZnO (3:1 wt%) before annealing (1.78 cd/A) and after annealing (2.45 cd/A) having a brightness 643 and 776 cd/m2at a current density of 36.16 and 31.67 mA/cm2are observed, respectively. Current density–voltage and brightness–voltage characteristics indicate that addition of ZnO nanoparticles can facilitate electrical injection and charge transport. The thermal annealing is thought to result in the formation of an interfacial layer between emissive polymer film and cathode

Phosphorylation of LCRMP-1 by GSK3β Promotes Filopoda Formation, Migration and Invasion Abilities in Lung Cancer Cells

LCRMP-1, a novel isoform of CRMP-1, can promote cancer cell migration, invasion and associate with poor clinical outcome in patients with non-small-cell lung cancer (NSCLC). However, the underlying regulatory mechanisms of LCRMP-1 in cancer cell invasiveness still remain obscure. Here, we report that GSK3β can phosphorylate LCRMP-1 at Thr-628 in consensus sequences and this phosphorylation is crucial for function of LCRMP-1 to promote filopodia formation, migration and invasion in cancer cells. Impediment of Thr-628 phosphorylation attenuates the stimulatory effects of LCRMP-1 on filopodia forming, migration and invasion abilities in cancer cells; simultaneously, kinase-dead GSK3β diminishes regulation of LCRMP-1 on cancer cell invasion. Furthermore, we also found that patients with low-level Ser-9-phosphorylated GSK3β expression and high-level LCRMP-1 expression have worse overall survival than those with high-level inactive GSK3β expressions and low-level LCRMP-1 expressions (P<0.0001). Collectively, these results demonstrate that GSK3β-dependent phosphorylation of LCRMP-1 provides an important mechanism for regulation of LCRMP-1 on cancer cell invasiveness and clinical outcome

Impedance Control of a Pneumatic Muscles-Driven Ankle Rehabilitation Robot

Pneumatic muscle is a new type of flexible actuator with advantages in terms of light weight, large output power/weight ratio, good security, low price and clean. In this paper, an ankle rehabilitation robot with two degrees of freedom driven by pneumatic muscle is studied. The force control method with an impedance controller in outer loop and a position inner loop is proposed. The demand of rehabilitation torque is ensured through tracking forces of three pneumatic muscle actuators. In the simulation, the constant force and variable force are tracked with error less than 10 N. In the experiment, the force control method also achieved satisfactory results, which provides a good support for the application of the robot in the ankle rehabilitation