360 research outputs found
On the use of secondary rotors for vertical axis wind turbine power take off
This work introduces and explores the use of secondary rotors for vertical axis wind turbine power take-off. A parametric framework based on optimally designed secondary rotors is developed which calculates the maximum achievable efficiency of power conversion between the primary and secondary rotors. It is shown that practicable rotor designs can convert between 87% and 90% of primary rotor power to the secondary rotors whilst facilitating nacelle mass reductions between 85% and 87% compared to traditional reference turbine drivetrains
Intake_epis_food(): An R Function for Fitting a Bivariate Nonlinear Measurement Error Model to Estimate Usual and Energy Intake for Episodically Consumed Foods
We consider a Bayesian analysis using WinBUGS to estimate the distribution of usual intake for episodically consumed foods and energy (calories). The model uses measures of nutrition and energy intakes via a food frequency questionnaire along with repeated 24 hour recalls and adjusting covariates. In order to estimate the usual intake of the food, we phrase usual intake in terms of person-specific random effects, along with day-to-day variability in food and energy consumption. Three levels are incorporated in the model. The first level incorporates information about whether an individual reported consumption of a particular food item. The second level incorporates the amount of food consumption equalling to zero if not consumed, and the third level incorporates the amount of energy intake. Estimates of posterior means of parameters and distributions of usual intakes are obtained by using Markov chain Monte Carlo calculations which can be thought as mean estimates for frequentists. This R function reports to users point estimates and credible intervals for parameters in the model, samples from their posterior distribution, samples from the distribution of usual intake and usual energy intake, trace plots of parameters and summary statistics of usual intake, usual energy intake and energy adjusted usual intake
Statistical issues related to dietary intake as the response variable in intervention trials.
The focus of this paper is dietary intervention trials. We explore the statistical issues involved when the response variable, intake of a food or nutrient, is based on self-report data that are subject to inherent measurement error. There has been little work on handling error in this context. A particular feature of self-reported dietary intake data is that the error may be differential by intervention group. Measurement error methods require information on the nature of the errors in the self-report data. We assume that there is a calibration sub-study in which unbiased biomarker data are available. We outline methods for handling measurement error in this setting and use theory and simulations to investigate how self-report and biomarker data may be combined to estimate the intervention effect. Methods are illustrated using data from the Trial of Nonpharmacologic Intervention in the Elderly, in which the intervention was a sodium-lowering diet and the response was sodium intake. Simulations are used to investigate the methods under differential error, differing reliability of self-reports relative to biomarkers and different proportions of individuals in the calibration sub-study. When the reliability of self-report measurements is comparable with that of the biomarker, it is advantageous to use the self-report data in addition to the biomarker to estimate the intervention effect. If, however, the reliability of the self-report data is low compared with that in the biomarker, then, there is little to be gained by using the self-report data. Our findings have important implications for the design of dietary intervention trials. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd
A new multivariate measurement error model with zero-inflated dietary data, and its application to dietary assessment
In the United States the preferred method of obtaining dietary intake data is
the 24-hour dietary recall, yet the measure of most interest is usual or
long-term average daily intake, which is impossible to measure. Thus, usual
dietary intake is assessed with considerable measurement error. Also, diet
represents numerous foods, nutrients and other components, each of which have
distinctive attributes. Sometimes, it is useful to examine intake of these
components separately, but increasingly nutritionists are interested in
exploring them collectively to capture overall dietary patterns. Consumption of
these components varies widely: some are consumed daily by almost everyone on
every day, while others are episodically consumed so that 24-hour recall data
are zero-inflated. In addition, they are often correlated with each other.
Finally, it is often preferable to analyze the amount of a dietary component
relative to the amount of energy (calories) in a diet because dietary
recommendations often vary with energy level. The quest to understand overall
dietary patterns of usual intake has to this point reached a standstill. There
are no statistical methods or models available to model such complex
multivariate data with its measurement error and zero inflation. This paper
proposes the first such model, and it proposes the first workable solution to
fit such a model. After describing the model, we use survey-weighted MCMC
computations to fit the model, with uncertainty estimation coming from balanced
repeated replication.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS446 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Clinical translation of a click-labeled 18F-octreotate radioligand for imaging neuroendocrine tumors
© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc. We conducted the first-in-human study of 18F-fluoroethyl triazole [Tyr3] octreotate (18F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137-163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed wholebody PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18F-FET-βAGTOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent
The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth
The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis. Changes in phosphocholine cellular levels following treatment could be detected non-invasively in tumor xenografts by [18F]-fluoromethyl-[1,2–2H4]-choline positron emission tomography. Herein, we reveal a previously unappreciated effect of choline metabolism on mitochondria function. Comparative metabolomics demonstrated that phosphatidylcholine pathway inhibition leads to a metabolically stressed phenotype analogous to mitochondria toxin treatment but without reactive oxygen species activation. Drug treatment decreased mitochondria function with associated reduction of citrate synthase expression and AMPK activation. Glucose and acetate uptake were increased in an attempt to overcome the metabolic stress. This study indicates that choline pathway pharmacological inhibition critically affects the metabolic function of the cell beyond reduced synthesis of phospholipids
The Future of Our Seas: Marine scientists and creative professionals collaborate for science communication
To increase awareness of the current challenges facing the marine environment,
the Future of Our Seas (FOOS) project brought together the expertise of
scientists, public engagement experts and creatives to train and support a
group of marine scientists in effective science communication and innovative
public engagement. This case study aims to inspire scientists and artists to
use the FOOS approach in training, activity design and development support
(hereafter called the ‘FOOS programme’) to collaboratively deliver novel
and creative engagement activities. The authors reflect on the experiences
of the marine scientists: (1) attending the FOOS communication and
engagement training; (2) creating and delivering public engagement activities;
(3) understanding our audience; and (4) collaborating with artists. The authors
also share what the artists and audiences learned from participating in the
FOOS public engagement activities. These different perspectives provide new
insights for the field with respect to designing collaborative training which
maximizes the impact of the training on participants, creative collaborators and
the public. Long-term benefits of taking part in the FOOS programme, such as
initiating future collaborative engagement activities and positively impacting
the scientists’ research processes, are also highlighted
Expert consensus document: Semantics in active surveillance for men with localized prostate cancer — results of a modified Delphi consensus procedure
Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if ≥70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making
5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer
The authors would like to acknowledge the support of The University of Cambridge, Cancer Research UK (CRUK SEB-Institute Group Award A ref10182; CRUK Senior fellowship C10112/A11388 to AEKI) and Hutchison Whampoa Limited. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. FF is a ULB Professor funded by grants from the F.N.R.S. and Télévie, the IUAP P7/03 programme, the ARC (AUWB-2010-2015 ULB-No 7), the WB Health program and the Fonds Gaston Ithier. Data access: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jpwzvsowiyuamzs&acc=GSE47592Background : The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced in proliferating cells such as colon tumours and the gut crypt progenitors, from which tumours can arise. Results : Here, we show that colorectal tumours and cancer cells express Ten-Eleven-Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells. Conclusions : Together our results indicate that promoters that acquire 5hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5hmC in tumours. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation.Publisher PDFPeer reviewe
Reporting Magnetic Resonance Imaging in Men on Active Surveillance for Prostate Cancer : The PRECISE Recommendations-A Report of a European School of Oncology Task Force
Background: Published data on prostate magnetic resonance imaging (MRI) during follow-up of men on active surveillance are lacking. Current guidelines for prostate MRI reporting concentrate on prostate cancer (PCa) detection and staging. A standardised approach to prostate MRI reporting for active surveillance will facilitate the robust collection of evidence in this newly developing area. Objective: To develop preliminary recommendations for reporting of individual MRI studies in men on active surveillance and for researchers reporting the outcomes of cohorts of men having MRI on active surveillance. Design, setting, and participants: The RAND/UCLA Appropriateness Method was used. Experts in urology, radiology, and radiation oncology developed a set of 394 statements relevant to prostate MRI reporting in men on active surveillance for PCa. Each statement was scored for agreement on a 9-point scale by each panellist prior to a panel meeting. Each statement was discussed and rescored at the meeting. Outcome measurements and statistical analysis: Measures of agreement and consensus were calculated for each statement. The most important statements, derived from both group discussion and scores of agreement and consensus, were used to create the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) checklist and case report form. Results and limitations: Key recommendations include reporting the index lesion size using absolute values at baseline and at each subsequent MRI. Radiologists should assess the likelihood of true change over time (ie, change in size or change in lesion characteristics on one or more sequences) on a 1-5 scale. A checklist of items for reporting a cohort of men on active surveillance was developed. These items were developed based on expert consensus in many areas in which data are lacking, and they are expected to develop and change as evidence is accrued. Conclusions: The PRECISE recommendations are designed to facilitate the development of a robust evidence database for documenting changes in prostateMRI findings over time ofmen on active surveillance. If used, they will facilitate data collection to distinguish-measurement error and natural variability in MRI appearances from true radiologic progression. Patient summary: Few published reports are available on how to use and interpret magnetic resonance imaging for men on active surveillance for prostate cancer. The PRECISE panel recommends that data should be collected in a standardised manner so that natural variation in the appearance and measurement of cancer over time can be distinguished from changes indicating significant tumour progression. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewe
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