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Sample records for comprehensive biomarker study

  1. Microbial ecology of the stratified water column of the Black Sea as revealed by a comprehensive biomarker study

    DEFF Research Database (Denmark)

    Wakeham, Stuart G.; Amann, Rudi; Freemann, Katherine H.

    2007-01-01

    The stratified water column of the Black Sea is partitioned into oxic, suboxic, and euxinic zones, each characterized by different biogeochemical processes and by distinct microbial communities. In 2003, we collected particulate matter by large volume in situ filtration at the highest resolution...... reduction, and sulfide oxidation at the chemocline, and bacterial sulfate reduction and anaerobic oxidation of methane by archaea in the anoxic zone. Cell densities for archaea and sulfate reducing bacteria are estimated based on water column biomarker concentrations and compared with CARD-FISH results....

  2. From the endometrium physiology to a comprehensive strategy for the discovery of ovarian cancer biomarkers

    OpenAIRE

    Janos L. Tanyi; Nathalie Scholler

    2011-01-01

    The development of comprehensive strategies for biomarker discovery of gynecological cancers is needed. The unique physiology of the female genital track revolves around ovulatory cycles ending by the proteolysis of the endometrium triggered by progesterone decline during the last part of the luteal phase. Building on the known link between incessant ovulation and ovarian cancer, we hypothesize that life-long menstruations could damage neighboring organs such as fallopian tubes, ovaries and p...

  3. Circulating biomarkers for predicting cardiovascular disease risk; a systematic review and comprehensive overview of meta-analyses.

    Directory of Open Access Journals (Sweden)

    Thijs C van Holten

    Full Text Available BACKGROUND: Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers. METHODS AND FINDINGS: Medline and Embase were screened on search terms that were related to "arterial ischemic events" and "meta-analyses". The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses. CONCLUSIONS: For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a

  4. Comprehensive serum profiling for the discovery of epithelial ovarian cancer biomarkers.

    Directory of Open Access Journals (Sweden)

    Ping Yip

    Full Text Available FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring and recurrence and OVA1, a multivariate panel consisting of CA-125 and four additional biomarkers, for referring patients to a specialist. Due to relatively poor performance of these tests, more accurate and broadly applicable biomarkers are needed. We evaluated the dysregulation of 259 candidate cancer markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under a single well-defined protocol. All stages of ovarian cancer and common benign gynecological conditions were represented. To ensure consistency and comparability of biomarker comparisons, all measurements were performed on a single platform, at a single site, using a panel of rigorously calibrated, qualified, high-throughput, multiplexed immunoassays and all analyses were conducted using the same software. Each marker was evaluated independently for its ability to differentiate ovarian cancer from benign conditions. A total of 175 markers were dysregulated in the cancer samples. HE4 (AUC=0.933 and CA-125 (AUC=0.907 were the most informative biomarkers, followed by IL-2 receptor α, α1-antitrypsin, C-reactive protein, YKL-40, cellular fibronectin, CA-72-4 and prostasin (AUC>0.800. To improve the discrimination between cancer and benign conditions, a simple multivariate combination of markers was explored using logistic regression. When combined into a single panel, the nine most informative individual biomarkers yielded an AUC value of 0.950, significantly higher than obtained when combining the markers in the OVA1 panel (AUC 0.912. Additionally, at a threshold sensitivity of 90%, the combination of the top 9 markers gave 88.9% specificity compared to 63.4% specificity for the OVA1 markers. Although a blinded validation study has not yet been performed, these results indicate that alternative biomarker combinations might lead to significant improvements in the

  5. A Comprehensive Workflow of Mass Spectrometry-Based Untargeted Metabolomics in Cancer Metabolic Biomarker Discovery Using Human Plasma and Urine

    Directory of Open Access Journals (Sweden)

    Jianwen She

    2013-09-01

    Full Text Available Current available biomarkers lack sensitivity and/or specificity for early detection of cancer. To address this challenge, a robust and complete workflow for metabolic profiling and data mining is described in details. Three independent and complementary analytical techniques for metabolic profiling are applied: hydrophilic interaction liquid chromatography (HILIC–LC, reversed-phase liquid chromatography (RP–LC, and gas chromatography (GC. All three techniques are coupled to a mass spectrometer (MS in the full scan acquisition mode, and both unsupervised and supervised methods are used for data mining. The univariate and multivariate feature selection are used to determine subsets of potentially discriminative predictors. These predictors are further identified by obtaining accurate masses and isotopic ratios using selected ion monitoring (SIM and data-dependent MS/MS and/or accurate mass MSn ion tree scans utilizing high resolution MS. A list combining all of the identified potential biomarkers generated from different platforms and algorithms is used for pathway analysis. Such a workflow combining comprehensive metabolic profiling and advanced data mining techniques may provide a powerful approach for metabolic pathway analysis and biomarker discovery in cancer research. Two case studies with previous published data are adapted and included in the context to elucidate the application of the workflow.

  6. From the endometrium physiology to a comprehensive strategy for the discovery of ovarian cancer biomarkers

    Directory of Open Access Journals (Sweden)

    Janos L. Tanyi

    2011-12-01

    Full Text Available The development of comprehensive strategies for biomarker discovery of gynecological cancers is needed. The unique physiology of the female genital track revolves around ovulatory cycles ending by the proteolysis of the endometrium triggered by progesterone decline during the last part of the luteal phase. Building on the known link between incessant ovulation and ovarian cancer, we hypothesize that life-long menstruations could damage neighboring organs such as fallopian tubes, ovaries and peritoneum via endometrial secretions, and thus endometrium neighboring structures may have developed highly efficient protective strategies that could, in turn, be hijacked by cancer cells for survival and invasion. After literature review, we could classify the molecules involved in ovulation and menstruation pathways in three main categories: proteases, proteases inhibitors and cell-surface protectors. Strikingly, all validated biomarkers for ovarian cancers belong to at least one of these categories. We thus propose the development of comprehensive methods for identification of early diagnostic markers for gynecological cancers using systematical mapping and characterization of surface or soluble molecules belonging to physiological pathways linked to menstruation and differently expressed during luteal cycles.

  7. Comprehensive Analysis of MILE Gene Expression Data Set Advances Discovery of Leukaemia Type and Subtype Biomarkers.

    Science.gov (United States)

    Labaj, Wojciech; Papiez, Anna; Polanski, Andrzej; Polanska, Joanna

    2017-03-01

    Large collections of data in studies on cancer such as leukaemia provoke the necessity of applying tailored analysis algorithms to ensure supreme information extraction. In this work, a custom-fit pipeline is demonstrated for thorough investigation of the voluminous MILE gene expression data set. Three analyses are accomplished, each for gaining a deeper understanding of the processes underlying leukaemia types and subtypes. First, the main disease groups are tested for differential expression against the healthy control as in a standard case-control study. Here, the basic knowledge on molecular mechanisms is confirmed quantitatively and by literature references. Second, pairwise comparison testing is performed for juxtaposing the main leukaemia types among each other. In this case by means of the Dice coefficient similarity measure the general relations are pointed out. Moreover, lists of candidate main leukaemia group biomarkers are proposed. Finally, with this approach being successful, the third analysis provides insight into all of the studied subtypes, followed by the emergence of four leukaemia subtype biomarkers. In addition, the class enhanced DEG signature obtained on the basis of novel pipeline processing leads to significantly better classification power of multi-class data classifiers. The developed methodology consisting of batch effect adjustment, adaptive noise and feature filtration coupled with adequate statistical testing and biomarker definition proves to be an effective approach towards knowledge discovery in high-throughput molecular biology experiments.

  8. Early-Phase Studies of Biomarkers

    DEFF Research Database (Denmark)

    Pepe, Margaret S.; Janes, Holly; Li, Christopher I.

    2016-01-01

    of a positive biomarker test in cases (true positive) to cost associated with a positive biomarker test in controls (false positive). Guidance is offered on soliciting the cost/benefit ratio. The calculations are based on the longstanding decision theory concept of providing a net benefit on average...... impact on patient outcomes of using the biomarker to make clinical decisions....

  9. Imaging biomarker roadmap for cancer studies

    NARCIS (Netherlands)

    O'Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; Desouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, J. R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid G.; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel B.; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and

  10. Big-data-based edge biomarkers: study on dynamical drug sensitivity and resistance in individuals.

    Science.gov (United States)

    Zeng, Tao; Zhang, Wanwei; Yu, Xiangtian; Liu, Xiaoping; Li, Meiyi; Chen, Luonan

    2016-07-01

    Big-data-based edge biomarker is a new concept to characterize disease features based on biomedical big data in a dynamical and network manner, which also provides alternative strategies to indicate disease status in single samples. This article gives a comprehensive review on big-data-based edge biomarkers for complex diseases in an individual patient, which are defined as biomarkers based on network information and high-dimensional data. Specifically, we firstly introduce the sources and structures of biomedical big data accessible in public for edge biomarker and disease study. We show that biomedical big data are typically 'small-sample size in high-dimension space', i.e. small samples but with high dimensions on features (e.g. omics data) for each individual, in contrast to traditional big data in many other fields characterized as 'large-sample size in low-dimension space', i.e. big samples but with low dimensions on features. Then, we demonstrate the concept, model and algorithm for edge biomarkers and further big-data-based edge biomarkers. Dissimilar to conventional biomarkers, edge biomarkers, e.g. module biomarkers in module network rewiring-analysis, are able to predict the disease state by learning differential associations between molecules rather than differential expressions of molecules during disease progression or treatment in individual patients. In particular, in contrast to using the information of the common molecules or edges (i.e.molecule-pairs) across a population in traditional biomarkers including network and edge biomarkers, big-data-based edge biomarkers are specific for each individual and thus can accurately evaluate the disease state by considering the individual heterogeneity. Therefore, the measurement of big data in a high-dimensional space is required not only in the learning process but also in the diagnosing or predicting process of the tested individual. Finally, we provide a case study on analyzing the temporal expression

  11. Biomarkers in Urachal Cancer and Adenocarcinomas in the Bladder: A Comprehensive Review Supplemented by Own Data

    Directory of Open Access Journals (Sweden)

    Henning Reis

    2018-01-01

    Full Text Available Urachal cancer (UrC is a rare but aggressive cancer. Due to overlapping histomorphology, discrimination of urachal from primary bladder adenocarcinomas (PBAC and adenocarcinomas secondarily involving the bladder (particularly colorectal adenocarcinomas, CRC can be challenging. Therefore, we aimed to give an overview of helpful (immunohistochemical biomarkers and clinicopathological factors in addition to survival analyses and included institutional data from 12 urachal adenocarcinomas. A PubMed search yielded 319 suitable studies since 1930 in the English literature with 1984 cases of UrC including 1834 adenocarcinomas (92% and 150 nonadenocarcinomas (8%. UrC was more common in men (63%, showed a median age at diagnosis of 50.8 years and a median tumor size of 6.0 cm. No associations were noted for overall survival and progression-free survival (PFS and clinicopathological factors beside a favorable PFS in male patients (p=0.047. The immunohistochemical markers found to be potentially helpful in the differential diagnostic situation are AMACR and CK34βE12 (UrC versus CRC and PBAC, CK7, β-Catenin and CD15 (UrC and PBAC versus CRC, and CEA and GATA3 (UrC and CRC versus PBAC. Serum markers like CEA, CA19-9 and CA125 might additionally be useful in the follow-up and monitoring of UrC.

  12. Comprehensive Analysis of Gene Expression Profiles of Sepsis-Induced Multiorgan Failure Identified Its Valuable Biomarkers.

    Science.gov (United States)

    Wang, Yumei; Yin, Xiaoling; Yang, Fang

    2018-02-01

    Sepsis is an inflammatory-related disease, and severe sepsis would induce multiorgan dysfunction, which is the most common cause of death of patients in noncoronary intensive care units. Progression of novel therapeutic strategies has proven to be of little impact on the mortality of severe sepsis, and unfortunately, its mechanisms still remain poorly understood. In this study, we analyzed gene expression profiles of severe sepsis with failure of lung, kidney, and liver for the identification of potential biomarkers. We first downloaded the gene expression profiles from the Gene Expression Omnibus and performed preprocessing of raw microarray data sets and identification of differential expression genes (DEGs) through the R programming software; then, significantly enriched functions of DEGs in lung, kidney, and liver failure sepsis samples were obtained from the Database for Annotation, Visualization, and Integrated Discovery; finally, protein-protein interaction network was constructed for DEGs based on the STRING database, and network modules were also obtained through the MCODE cluster method. As a result, lung failure sepsis has the highest number of DEGs of 859, whereas the number of DEGs in kidney and liver failure sepsis samples is 178 and 175, respectively. In addition, 17 overlaps were obtained among the three lists of DEGs. Biological processes related to immune and inflammatory response were found to be significantly enriched in DEGs. Network and module analysis identified four gene clusters in which all or most of genes were upregulated. The expression changes of Icam1 and Socs3 were further validated through quantitative PCR analysis. This study should shed light on the development of sepsis and provide potential therapeutic targets for sepsis-induced multiorgan failure.

  13. A Comprehensive Peptidome Profiling Technology for the Identification of Early Detection Biomarkers for Lung Adenocarcinoma

    Science.gov (United States)

    Ueda, Koji; Saichi, Naomi; Takami, Sachiko; Kang, Daechun; Toyama, Atsuhiko; Daigo, Yataro; Ishikawa, Nobuhisa; Kohno, Nobuoki; Tamura, Kenji; Shuin, Taro; Nakayama, Masato; Sato, Taka-Aki; Nakamura, Yusuke; Nakagawa, Hidewaki

    2011-01-01

    The mass spectrometry-based peptidomics approaches have proven its usefulness in several areas such as the discovery of physiologically active peptides or biomarker candidates derived from various biological fluids including blood and cerebrospinal fluid. However, to identify biomarkers that are reproducible and clinically applicable, development of a novel technology, which enables rapid, sensitive, and quantitative analysis using hundreds of clinical specimens, has been eagerly awaited. Here we report an integrative peptidomic approach for identification of lung cancer-specific serum peptide biomarkers. It is based on the one-step effective enrichment of peptidome fractions (molecular weight of 1,000–5,000) with size exclusion chromatography in combination with the precise label-free quantification analysis of nano-LC/MS/MS data set using Expressionist proteome server platform. We applied this method to 92 serum samples well-managed with our SOP (standard operating procedure) (30 healthy controls and 62 lung adenocarcinoma patients), and quantitatively assessed the detected 3,537 peptide signals. Among them, 118 peptides showed significantly altered serum levels between the control and lung cancer groups (p5.0). Subsequently we identified peptide sequences by MS/MS analysis and further assessed the reproducibility of Expressionist-based quantification results and their diagnostic powers by MRM-based relative-quantification analysis for 96 independently prepared serum samples and found that APOA4 273–283, FIBA 5–16, and LBN 306–313 should be clinically useful biomarkers for both early detection and tumor staging of lung cancer. Our peptidome profiling technology can provide simple, high-throughput, and reliable quantification of a large number of clinical samples, which is applicable for diverse peptidome-targeting biomarker discoveries using any types of biological specimens. PMID:21533267

  14. HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

    Science.gov (United States)

    Castellsagué, Xavier; Alemany, Laia; Quer, Miquel; Halec, Gordana; Quirós, Beatriz; Tous, Sara; Clavero, Omar; Alòs, Llúcia; Biegner, Thorsten; Szafarowski, Tomasz; Alejo, Maria; Holzinger, Dana; Cadena, Enrique; Claros, Edith; Hall, Gillian; Laco, Jan; Poljak, Mario; Benevolo, Maria; Kasamatsu, Elena; Mehanna, Hisham; Ndiaye, Cathy; Guimerà, Núria; Lloveras, Belen; León, Xavier; Ruiz-Cabezas, Juan C; Alvarado-Cabrero, Isabel; Kang, Chang-Suk; Oh, Jin-Kyoung; Garcia-Rojo, Marcial; Iljazovic, Ermina; Ajayi, Oluseyi F; Duarte, Flora; Nessa, Ashrafun; Tinoco, Leopoldo; Duran-Padilla, Marco A; Pirog, Edyta C; Viarheichyk, Halina; Morales, Hesler; Costes, Valérie; Félix, Ana; Germar, Maria Julieta V; Mena, Marisa; Ruacan, Arzu; Jain, Asha; Mehrotra, Ravi; Goodman, Marc T; Lombardi, Luis Estuardo; Ferrera, Annabelle; Malami, Sani; Albanesi, Estela I; Dabed, Pablo; Molina, Carla; López-Revilla, Rubén; Mandys, Václav; González, Manuel E; Velasco, Julio; Bravo, Ignacio G; Quint, Wim; Pawlita, Michael; Muñoz, Nubia; de Sanjosé, Silvia; Xavier Bosch, F

    2016-06-01

    We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy

    Science.gov (United States)

    Satoh, Minoru; Tanaka, Shin; Ceribelli, Angela; Calise, S. John; Chan, Edward K. L.

    2018-01-01

    Autoantibodies specific for idiopathic inflammatory myopathy (myositis-specific autoantibodies (MSAs)) are clinically useful biomarkers to help the diagnosis of polymyositis/dermatomyositis (PM/DM). Many of these are also associated with a unique clinical subset of PM/DM, making them useful in predicting and monitoring certain clinical manifestations. Classic MSAs known for over 30 years include antibodies to Jo-1 (histidyl transfer RNA (tRNA) synthetase) and other aminoacyl tRNA synthetases (ARS), anti-Mi-2, and anti-signal recognition particle (SRP). Anti-Jo-1 is the first autoantibodies to ARS detected in 15–25 % of patients. In addition to anti-Jo-1, antibodies to seven other aminoacyl tRNA synthetases (ARS) have been reported with prevalence, usually 1–5 % or lower. Patients with any antiARS antibodies are associated with anti-synthetase syndrome characterized by myositis, interstitial lung disease (ILD), arthritis, Raynaud’s phenomenon, and others. Several recent studies suggested heterogeneity in clinical features among different anti-ARS antibody-positive patients and anti-ARS may also be found in idiopathic ILD without myositis. Anti-Mi-2 is a classic marker for DM and associated with good response to steroid treatment and good prognosis. Anti-SRP is specific for PM and associated with treatment-resistant myopathy histologically characterized as necrotizing myopathy. In addition to classic MSAs, several new autoantibodies with strong clinical significance have been described in DM. Antibodies to transcription intermediary factor 1γ/α (TIF1γ/α, p155/140) are frequently found in DM associated with malignancy while anti-melanoma differentiation-associated gene 5 (MDA5; CADM140) are associated with clinically amyopathic DM (CADM) complicated by rapidly progressive ILD. Also, anti-MJ/nuclear matrix protein 2 (NXP-2) and anti-small ubiquitin-like modifier-1 (SUMO-1) activating enzyme (SAE) are recognized as new DM-specific autoantibodies. Addition of

  16. Cooling tower drift: comprehensive case study

    International Nuclear Information System (INIS)

    Laulainen, N.S.; Ulanski, S.L.

    1979-01-01

    A comprehensive experiment to study drift from mechanical drift cooling towers was conducted during June 1978 at the PG and E Pittsburg Power Plant. The data from this study will be used for validation of drift deposition models. Preliminary results show the effects of tower geometry and orientation with respect to the wind and to single- or two-tower operation. The effect of decreasing relative humidity during a test run can also be seen

  17. Biomarkers in differentiating clinical dengue cases: A prospective cohort study

    Directory of Open Access Journals (Sweden)

    Gary Kim Kuan Low

    2015-12-01

    Full Text Available Objective: To evaluate five biomarkers (neopterin, vascular endothelial growth factor-A, thrombomodulin, soluble vascular cell adhesion molecule 1 and pentraxin 3 in differentiating clinical dengue cases. Methods: A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’ follow-up. All patients included in the study were 15 years old or older, not pregnant, not infected by dengue previously and did not have cancer, autoimmune or haematological disorder. Median test was performed to compare the biomarker levels. A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases. Monte Carlo method was used to estimate the 2-tailed probability (P value for independent variables with unequal number of patients. Results: All biomarkers except thrombomodulin has P value < 0.001 in differentiating among the healthy subjects, non-dengue fever, dengue without warning signs and dengue with warning signs/severe dengue. Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A (P < 0.05. Conclusions: Certain biomarkers were able to differentiate the clinical dengue cases. This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.

  18. Comprehensive Evaluation of TFF3 Promoter Hypomethylation and Molecular Biomarker Potential for Prostate Cancer Diagnosis and Prognosis

    DEFF Research Database (Denmark)

    Nørgaard, Maibritt; Haldrup, Christa; Storebjerg, Tine Maj

    2017-01-01

    Overdiagnosis and overtreatment of clinically insignificant tumors remains a major problem in prostate cancer (PC) due to suboptimal diagnostic and prognostic tools. Thus, novel biomarkers are urgently needed. In this study, we investigated the biomarker potential of Trefoil factor 3 (TFF3......) promoter methylation and RNA expression levels for PC. Initially, by quantitative methylation specific PCR (qMSP) analysis of a large radical prostatectomy (RP) cohort (n = 292), we found that the TFF3 promoter was significantly hypomethylated in PC compared to non-malignant (NM) prostate tissue samples (p....... 67 NM) analyzed by Illumina 450K DNA methylation arrays and/or RNA sequencing. TFF3 promoter methylation and transcriptional expression levels were inversely correlated, suggesting that epigenetic mechanisms contribute to the regulation of gene activity. Furthermore, low TFF3 expression...

  19. Cardiovascular biomarkers in clinical studies of type 2 diabetes

    DEFF Research Database (Denmark)

    Baldassarre, M P A; Andersen, A; Consoli, A

    2018-01-01

    biomarkers and 3) novel biomarkers (oxidative stress and endothelial dysfunction biomarkers). Within each category we present the currently best validated biomarkers with special focus on the population of interest (type 2 diabetes). For each individual biomarker, the physiological role, the validation...

  20. Urine stability studies for novel biomarkers of acute kidney injury.

    Science.gov (United States)

    Parikh, Chirag R; Butrymowicz, Isabel; Yu, Angela; Chinchilli, Vernon M; Park, Meyeon; Hsu, Chi-Yuan; Reeves, W Brian; Devarajan, Prasad; Kimmel, Paul L; Siew, Edward D; Liu, Kathleen D

    2014-04-01

    The study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers. Cross-sectional prospective. Hospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36). We tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4°C for 48 hours before freezing at -80°C, (2) centrifugation and storage at 25°C for 48 hours before freezing at -80°C, and (3) uncentrifuged samples immediately frozen at -80°C. Urine concentrations of 5 biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C. We measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at -80°C was compared using concordance correlation coefficients (CCCs). Neither storing samples at 4°C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25°C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25°C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96). No comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors. All candidate markers tested using the specified assays showed high stability with both short-term storage at 4°C and without centrifugation

  1. Humor comprehension and appreciation: an FMRI study.

    Science.gov (United States)

    Bartolo, Angela; Benuzzi, Francesca; Nocetti, Luca; Baraldi, Patrizia; Nichelli, Paolo

    2006-11-01

    Humor is a unique ability in human beings. Suls [A two-stage model for the appreciation of jokes and cartoons. In P. E. Goldstein & J. H. McGhee (Eds.), The psychology of humour. Theoretical perspectives and empirical issues. New York: Academic Press, 1972, pp. 81-100] proposed a two-stage model of humor: detection and resolution of incongruity. Incongruity is generated when a prediction is not confirmed in the final part of a story. To comprehend humor, it is necessary to revisit the story, transforming an incongruous situation into a funny, congruous one. Patient and neuroimaging studies carried out until now lead to different outcomes. In particular, patient studies found that right brain-lesion patients have difficulties in humor comprehension, whereas neuroimaging studies suggested a major involvement of the left hemisphere in both humor detection and comprehension. To prevent activation of the left hemisphere due to language processing, we devised a nonverbal task comprising cartoon pairs. Our findings demonstrate activation of both the left and the right hemispheres when comparing funny versus nonfunny cartoons. In particular, we found activation of the right inferior frontal gyrus (BA 47), the left superior temporal gyrus (BA 38), the left middle temporal gyrus (BA 21), and the left cerebellum. These areas were also activated in a nonverbal task exploring attribution of intention [Brunet, E., Sarfati, Y., Hardy-Bayle, M. C., & Decety, J. A PET investigation of the attribution of intentions with a nonverbal task. Neuroimage, 11, 157-166, 2000]. We hypothesize that the resolution of incongruity might occur through a process of intention attribution. We also asked subjects to rate the funniness of each cartoon pair. A parametric analysis showed that the left amygdala was activated in relation to subjective amusement. We hypothesize that the amygdala plays a key role in giving humor an emotional dimension.

  2. Accounting for control mislabeling in case-control biomarker studies.

    Science.gov (United States)

    Rantalainen, Mattias; Holmes, Chris C

    2011-12-02

    In biomarker discovery studies, uncertainty associated with case and control labels is often overlooked. By omitting to take into account label uncertainty, model parameters and the predictive risk can become biased, sometimes severely. The most common situation is when the control set contains an unknown number of undiagnosed, or future, cases. This has a marked impact in situations where the model needs to be well-calibrated, e.g., when the prediction performance of a biomarker panel is evaluated. Failing to account for class label uncertainty may lead to underestimation of classification performance and bias in parameter estimates. This can further impact on meta-analysis for combining evidence from multiple studies. Using a simulation study, we outline how conventional statistical models can be modified to address class label uncertainty leading to well-calibrated prediction performance estimates and reduced bias in meta-analysis. We focus on the problem of mislabeled control subjects in case-control studies, i.e., when some of the control subjects are undiagnosed cases, although the procedures we report are generic. The uncertainty in control status is a particular situation common in biomarker discovery studies in the context of genomic and molecular epidemiology, where control subjects are commonly sampled from the general population with an established expected disease incidence rate.

  3. Ionizing radiation biomarkers for potential use in epidemiological studies

    International Nuclear Information System (INIS)

    Pernot, Eileen; Cardis, Elisabeth; Hall, Janet; Baatout, Sarah; El Saghire, Houssein; Mohammed Abderrafi Benotmane; Roel Quintens; Blanchardon, Eric; Bouffler, Simon; Gomolka, Maria; Guertler, Anne; Kreuzer, Michaela; Harms-Ringdahl, Mats; Jeggo, Penny; Laurier, Dominique; Lindholm, Carita; Mkacher, Radhia; Sabatier, Laure; Tapio, Soile; De Vathaire, Florent

    2012-01-01

    Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100 mSv and/or 0.1 mSv min -1 ) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of

  4. Clinical studies of biomarkers in suicide prediction

    OpenAIRE

    Jokinen, Jussi

    2007-01-01

    Suicide is a major clinical problem in psychiatry and suicidal behaviours can be seen as a nosological entity per se. Predicting suicide is difficult due to its low base-rate and the limited specificity of clinical predictors. Prospective biological studies suggest that dysfunctions in the hypothalamo pituitary adrenal (HPA) axis and the serotonergic system have predictive power for suicide in mood disorders. Suicide attempt is the most robust clinical predictor making suici...

  5. Development of a biomarkers database for the National Children's Study

    Energy Technology Data Exchange (ETDEWEB)

    Lobdell, Danelle T [US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Human Studies Division, Epidemiology and Biomarkers Branch, MD 58A, Research Triangle Park, NC 27711 (United States); Mendola, Pauline [US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Human Studies Division, Epidemiology and Biomarkers Branch, MD 58A, Research Triangle Park, NC 27711 (United States)

    2005-08-07

    The National Children's Study (NCS) is a federally-sponsored, longitudinal study of environmental influences on the health and development of children across the United States (www.nationalchildrensstudy.gov). Current plans are to study approximately 100,000 children and their families beginning before birth up to age 21 years. To explore potential biomarkers that could be important measurements in the NCS, we compiled the relevant scientific literature to identify both routine or standardized biological markers as well as new and emerging biological markers. Although the search criteria encouraged examination of factors that influence the breadth of child health and development, attention was primarily focused on exposure, susceptibility, and outcome biomarkers associated with four important child health outcomes: autism and neurobehavioral disorders, injury, cancer, and asthma. The Biomarkers Database was designed to allow users to: (1) search the biomarker records compiled by type of marker (susceptibility, exposure or effect), sampling media (e.g., blood, urine, etc.), and specific marker name; (2) search the citations file; and (3) read the abstract evaluations relative to our search criteria. A searchable, user-friendly database of over 2000 articles was created and is publicly available at: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=85844. PubMed was the primary source of references with some additional searches of Toxline, NTIS, and other reference databases. Our initial focus was on review articles, beginning as early as 1996, supplemented with searches of the recent primary research literature from 2001 to 2003. We anticipate this database will have applicability for the NCS as well as other studies of children's environmental health.

  6. Development of a biomarkers database for the National Children's Study

    International Nuclear Information System (INIS)

    Lobdell, Danelle T.; Mendola, Pauline

    2005-01-01

    The National Children's Study (NCS) is a federally-sponsored, longitudinal study of environmental influences on the health and development of children across the United States (www.nationalchildrensstudy.gov). Current plans are to study approximately 100,000 children and their families beginning before birth up to age 21 years. To explore potential biomarkers that could be important measurements in the NCS, we compiled the relevant scientific literature to identify both routine or standardized biological markers as well as new and emerging biological markers. Although the search criteria encouraged examination of factors that influence the breadth of child health and development, attention was primarily focused on exposure, susceptibility, and outcome biomarkers associated with four important child health outcomes: autism and neurobehavioral disorders, injury, cancer, and asthma. The Biomarkers Database was designed to allow users to: (1) search the biomarker records compiled by type of marker (susceptibility, exposure or effect), sampling media (e.g., blood, urine, etc.), and specific marker name; (2) search the citations file; and (3) read the abstract evaluations relative to our search criteria. A searchable, user-friendly database of over 2000 articles was created and is publicly available at: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=85844. PubMed was the primary source of references with some additional searches of Toxline, NTIS, and other reference databases. Our initial focus was on review articles, beginning as early as 1996, supplemented with searches of the recent primary research literature from 2001 to 2003. We anticipate this database will have applicability for the NCS as well as other studies of children's environmental health

  7. Major depressive disorder: insight into candidate cerebrospinal fluid protein biomarkers from proteomics studies.

    Science.gov (United States)

    Al Shweiki, Mhd Rami; Oeckl, Patrick; Steinacker, Petra; Hengerer, Bastian; Schönfeldt-Lecuona, Carlos; Otto, Markus

    2017-06-01

    Major Depressive Disorder (MDD) is the leading cause of global disability, and an increasing body of literature suggests different cerebrospinal fluid (CSF) proteins as biomarkers of MDD. The aim of this review is to summarize the suggested CSF biomarkers and to analyze the MDD proteomics studies of CSF and brain tissues for promising biomarker candidates. Areas covered: The review includes the human studies found by a PubMed search using the following terms: 'depression cerebrospinal fluid biomarker', 'major depression biomarker CSF', 'depression CSF biomarker', 'proteomics depression', 'proteomics biomarkers in depression', 'proteomics CSF biomarker in depression', and 'major depressive disorder CSF'. The literature analysis highlights promising biomarker candidates and demonstrates conflicting results on others. It reveals 42 differentially regulated proteins in MDD that were identified in more than one proteomics study. It discusses the diagnostic potential of the biomarker candidates and their association with the suggested pathologies. Expert commentary: One ultimate goal of finding biomarkers for MDD is to improve the diagnostic accuracy to achieve better treatment outcomes; due to the heterogeneous nature of MDD, using bio-signatures could be a good strategy to differentiate MDD from other neuropsychiatric disorders. Notably, further validation studies of the suggested biomarkers are still needed.

  8. Halifax Lateral Pipeline Project : comprehensive study report

    International Nuclear Information System (INIS)

    1998-12-01

    The National Energy Board has requested the preparation of a comprehensive study report (CSR) for the proposed Halifax Lateral Pipeline Project in support of Maritimes and Northeast Pipeline Company's proposal to construct the lateral pipeline to transport natural gas produced in offshore Nova Scotia to the Tufts Cove electric generating station in the Halifax Regional Municipality. The project will also enhance the access of natural gas to potential markets located along the pipeline route. This CSR was prepared according to guidelines of the Canadian Environmental Assessment Agency. The report presents: (1) an overview of the project, (2) a summary of the regulatory requirements for assessment, (3) a description of the environmental assessment and regulatory process to date, (4) a summary of the predicted residual environmental and socio-economic effects associated with the project, and (5) a summary of the public consultation process. The environmental and socio-economic assessment focused on these eleven issues: groundwater resources, surface water resources, wetlands, soils, air quality, fish habitat, rare herpetiles, mammals, avifauna, rare plants and archaeological heritage resources. The report identified potential interactions between the project and valued socio-economic and environmental components. These were addressed in combination with recommended mitigative measures to reduce potential adverse effects. It was concluded that the overall environmental effects from the proposed project are likely to be minimal and can be effectively managed with good environmental management methods. 14 refs., 5 tabs., 5 figs., 2 appendices

  9. Hemostasis biomarkers and incident cognitive impairment: the REGARDS study.

    Science.gov (United States)

    Gillett, S R; McClure, L A; Callas, P W; Thacker, E L; Unverzagt, F W; Wadley, V G; Letter, A J; Cushman, M

    2018-05-07

    Vascular risk factors are associated with cognitive impairment, a condition with substantial public health burden. We hypothesized that hemostasis biomarkers related to vascular disease would be associated with risk of incident cognitive impairment. We performed a nested case control study including 1,082 participants with 3.5 years of follow-up in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a longitudinal cohort study of 30,239 black and white Americans ≥45 years old. Participants were free of stroke or cognitive impairment at baseline. Baseline D-dimer, fibrinogen, factor VIII, and protein C were measured in 495 cases who developed cognitive impairment during follow-up (based on abnormal scores on ≥2 of 3 cognitive tests) and 587 controls. Unadjusted ORs for incident cognitive impairment were 1.32 (95% CI 1.02, 1.70) for D-dimer >0.50 μg/mL, 1.83 (CI 1.24, 2.71) for fibrinogen >90 th percentile, 1.63 (CI 1.11, 2.38) for factor VIII >90 th percentile and 1.10 (CI 0.73, 1.65) for protein C impairment, with an adjusted OR 1.73 (CI 1.10, 2.69). Elevated D-dimer, fibrinogen, and factor VIII were not associated with occurrence of cognitive impairment after multivariable adjustment; however, having at least 2 abnormal biomarkers was associated, suggesting the burden of these biomarkers is relevant. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer.

    Science.gov (United States)

    Shukla, Hem D

    2017-10-25

    During the past century, our understanding of cancer diagnosis and treatment has been based on a monogenic approach, and as a consequence our knowledge of the clinical genetic underpinnings of cancer is incomplete. Since the completion of the human genome in 2003, it has steered us into therapeutic target discovery, enabling us to mine the genome using cutting edge proteogenomics tools. A number of novel and promising cancer targets have emerged from the genome project for diagnostics, therapeutics, and prognostic markers, which are being used to monitor response to cancer treatment. The heterogeneous nature of cancer has hindered progress in understanding the underlying mechanisms that lead to abnormal cellular growth. Since, the start of The Cancer Genome Atlas (TCGA), and the International Genome consortium projects, there has been tremendous progress in genome sequencing and immense numbers of cancer genomes have been completed, and this approach has transformed our understanding of the diagnosis and treatment of different types of cancers. By employing Genomics and proteomics technologies, an immense amount of genomic data is being generated on clinical tumors, which has transformed the cancer landscape and has the potential to transform cancer diagnosis and prognosis. A complete molecular view of the cancer landscape is necessary for understanding the underlying mechanisms of cancer initiation to improve diagnosis and prognosis, which ultimately will lead to personalized treatment. Interestingly, cancer proteome analysis has also allowed us to identify biomarkers to monitor drug and radiation resistance in patients undergoing cancer treatment. Further, TCGA-funded studies have allowed for the genomic and transcriptomic characterization of targeted cancers, this analysis aiding the development of targeted therapies for highly lethal malignancy. High-throughput technologies, such as complete proteome, epigenome, protein-protein interaction, and pharmacogenomics

  11. Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer

    Directory of Open Access Journals (Sweden)

    Hem D. Shukla

    2017-10-01

    Full Text Available During the past century, our understanding of cancer diagnosis and treatment has been based on a monogenic approach, and as a consequence our knowledge of the clinical genetic underpinnings of cancer is incomplete. Since the completion of the human genome in 2003, it has steered us into therapeutic target discovery, enabling us to mine the genome using cutting edge proteogenomics tools. A number of novel and promising cancer targets have emerged from the genome project for diagnostics, therapeutics, and prognostic markers, which are being used to monitor response to cancer treatment. The heterogeneous nature of cancer has hindered progress in understanding the underlying mechanisms that lead to abnormal cellular growth. Since, the start of The Cancer Genome Atlas (TCGA, and the International Genome consortium projects, there has been tremendous progress in genome sequencing and immense numbers of cancer genomes have been completed, and this approach has transformed our understanding of the diagnosis and treatment of different types of cancers. By employing Genomics and proteomics technologies, an immense amount of genomic data is being generated on clinical tumors, which has transformed the cancer landscape and has the potential to transform cancer diagnosis and prognosis. A complete molecular view of the cancer landscape is necessary for understanding the underlying mechanisms of cancer initiation to improve diagnosis and prognosis, which ultimately will lead to personalized treatment. Interestingly, cancer proteome analysis has also allowed us to identify biomarkers to monitor drug and radiation resistance in patients undergoing cancer treatment. Further, TCGA-funded studies have allowed for the genomic and transcriptomic characterization of targeted cancers, this analysis aiding the development of targeted therapies for highly lethal malignancy. High-throughput technologies, such as complete proteome, epigenome, protein–protein interaction

  12. Biomarkers of Acute Stroke Etiology (BASE) Study Methodology.

    Science.gov (United States)

    Jauch, Edward C; Barreto, Andrew D; Broderick, Joseph P; Char, Doug M; Cucchiara, Brett L; Devlin, Thomas G; Haddock, Alison J; Hicks, William J; Hiestand, Brian C; Jickling, Glen C; June, Jeff; Liebeskind, David S; Lowenkopf, Ted J; Miller, Joseph B; O'Neill, John; Schoonover, Tim L; Sharp, Frank R; Peacock, W Frank

    2017-05-05

    Acute ischemic stroke affects over 800,000 US adults annually, with hundreds of thousands more experiencing a transient ischemic attack. Emergent evaluation, prompt acute treatment, and identification of stroke or TIA (transient ischemic attack) etiology for specific secondary prevention are critical for decreasing further morbidity and mortality of cerebrovascular disease. The Biomarkers of Acute Stroke Etiology (BASE) study is a multicenter observational study to identify serum markers defining the etiology of acute ischemic stroke. Observational trial of patients presenting to the hospital within 24 h of stroke onset. Blood samples are collected at arrival, 24, and 48 h later, and RNA gene expression is utilized to identify stroke etiology marker candidates. The BASE study began January 2014. At the time of writing, there are 22 recruiting sites. Enrollment is ongoing, expected to hit 1000 patients by March 2017. The BASE study could potentially aid in focusing the initial diagnostic evaluation to determine stroke etiology, with more rapidly initiated targeted evaluations and secondary prevention strategies.Clinical Trial Registration Clinicaltrials.gov NCT02014896 https://clinicaltrials.gov/ct2/show/NCT02014896?term=biomarkers+of+acute+stroke+etiology&rank=1.

  13. Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study.

    Science.gov (United States)

    Shinozaki, Eiji; Yoshino, Takayuki; Yamazaki, Kentaro; Muro, Kei; Yamaguchi, Kensei; Nishina, Tomohiro; Yuki, Satoshi; Shitara, Kohei; Bando, Hideaki; Mimaki, Sachiyo; Nakai, Chikako; Matsushima, Koutatsu; Suzuki, Yutaka; Akagi, Kiwamu; Yamanaka, Takeharu; Nomura, Shogo; Fujii, Satoshi; Esumi, Hiroyasu; Sugiyama, Masaya; Nishida, Nao; Mizokami, Masashi; Koh, Yasuhiro; Abe, Yukiko; Ohtsu, Atsushi; Tsuchihara, Katsuya

    2017-11-07

    Patients with BRAF V600E -mutated metastatic colorectal cancer (mCRC) have a poorer prognosis as well as resistance to anti-EGFR antibodies. However, it is unclear whether BRAF mutations other than BRAF V600E (BRAF non-V600E mutations) contribute to anti-EGFR antibody resistance. This study was composed of exploratory and inference cohorts. Candidate biomarkers identified by whole exome sequencing from super-responders and nonresponders in the exploratory cohort were validated by targeted resequencing for patients who received anti-EGFR antibody in the inference cohort. In the exploratory cohort, 31 candidate biomarkers, including KRAS/NRAS/BRAF mutations, were identified. Targeted resequencing of 150 patients in the inference cohort revealed 40 patients with RAS (26.7%), 9 patients with BRAF V600E (6.0%), and 7 patients with BRAF non-V600E mutations (4.7%), respectively. The response rates in RAS, BRAF V600E , and BRAF non-V600E were lower than those in RAS/BRAF wild-type (2.5%, 0%, and 0% vs 31.9%). The median PFS in BRAF non-V600E mutations was 2.4 months, similar to that in RAS or BRAF V600E mutations (2.1 and 1.6 months) but significantly worse than that in wild-type RAS/BRAF (5.9 months). Although BRAF non-V600E mutations identified were a rare and unestablished molecular subtype, certain BRAF non-V600E mutations might contribute to a lesser benefit of anti-EGFR monoclonal antibody treatment.

  14. The PAXgene(® tissue system preserves phosphoproteins in human tissue specimens and enables comprehensive protein biomarker research.

    Directory of Open Access Journals (Sweden)

    Sibylle Gündisch

    Full Text Available Precise quantitation of protein biomarkers in clinical tissue specimens is a prerequisite for accurate and effective diagnosis, prognosis, and personalized medicine. Although progress is being made, protein analysis from formalin-fixed and paraffin-embedded tissues is still challenging. In previous reports, we showed that the novel formalin-free tissue preservation technology, the PAXgene Tissue System, allows the extraction of intact and immunoreactive proteins from PAXgene-fixed and paraffin-embedded (PFPE tissues. In the current study, we focused on the analysis of phosphoproteins and the applicability of two-dimensional gel electrophoresis (2D-PAGE and enzyme-linked immunosorbent assay (ELISA to the analysis of a variety of malignant and non-malignant human tissues. Using western blot analysis, we found that phosphoproteins are quantitatively preserved in PFPE tissues, and signal intensities are comparable to that in paired, frozen tissues. Furthermore, proteins extracted from PFPE samples are suitable for 2D-PAGE and can be quantified by ELISA specific for denatured proteins. In summary, the PAXgene Tissue System reliably preserves phosphoproteins in human tissue samples, even after prolonged fixation or stabilization times, and is compatible with methods for protein analysis such as 2D-PAGE and ELISA. We conclude that the PAXgene Tissue System has the potential to serve as a versatile tissue fixative for modern pathology.

  15. A developmental study of proverb comprehension.

    Science.gov (United States)

    Resnick, D A

    1982-09-01

    Growth in proverb comprehension was hypothesized to result from the gradual emergence of cognitive abilities reflected in a sequence of increasingly complex abilities: story matching, transfer of relations, desymbolization, proverb matching, and paraphrase. Items for these abilities for each of 10 proverbs of two structural types were administered in three test sessions to 438 students in grades three to seven. An analogy subtest was used to measure general intelligence. ANOVA yielded significant main effects for grade, tasks, and proverbs (all p's less than .01). A significant task x proverb interaction (p less than .01) revealed the difficulty of precise control over the language of the items. Proverb structure had no measurable impact on difficulty. Analogy score was a significant factor in performance (p less than .01) but not as potent as age (p less than .01). The sequential order of abilities received only weak confirmation, though tasks did correlate among themselves with medium strength (r's = .50-.70). Individual interviews added a qualitative dimension to the findings. The suitability of cognitive hierarchical models for proverb comprehension was questioned.

  16. Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis

    DEFF Research Database (Denmark)

    Teunissen, Charlotte; Menge, Til; Altintas, Ayse

    2013-01-01

    The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus......). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use...

  17. [Collaborative projects with academia for regulatory science studies on biomarkers].

    Science.gov (United States)

    Saito, Yoshiro; Nakamura, Ryosuke; Maekawa, Keiko

    2014-01-01

    Biomarkers are useful tools to be utilized as indicators/predictors of disease severity and drug responsiveness/safety, and thus are expected to promote efficient drug development and to accelerate proper use of approved drugs. Many academic achievements have been reported, but only a small number of biomarkers are used in clinical trials and drug treatments. Regulatory sciences on biomarkers for their secure development and proper qualification are necessary to facilitate their practical application. We started to collaborate with Tohoku University and Nagoya City University for sample quality, biomarker identification, evaluation of their usage, and making guidances. In this short review, scheme and progress of these projects are introduced.

  18. Smoking reduction and biomarkers in two longitudinal studies

    DEFF Research Database (Denmark)

    Godtfredsen, Nina; Prescott, Eva; Vestbo, Jørgen

    2006-01-01

    AIMS: To measure reduction in exposure to smoke in two population-based studies of self-reported smoking reduction not using nicotine replacement. DESIGN: Cross-sectional analyses of biomarkers and smoking. SETTING: Data from two time-points in the Copenhagen City Heart Study (CCHS), 1981....../83 and 1991/94, and the Copenhagen Male Study (CMS) in 1976 and 1985/86, respectively. PARTICIPANTS: There were 3026 adults who were smokers at both time-points in the CCHS and 1319 men smoking at both time-points in the CMS. MEASUREMENTS: Smoking status and tobacco consumption were assessed by self...... a reduction in cigarettes per day of 50% or more without quitting were compared with continuing medium, heavy and light smokers (1-14 g/day) using linear regression. Sex (CCHS only), age, self-reported inhalation of smoke, duration of smoking, type of tobacco and amount smoked were included as covariates...

  19. Circulating biomarkers for predicting cardiovascular disease risk : a systematic review and comprehensive overview of meta-analyses

    NARCIS (Netherlands)

    Holten, van T.C.; Waanders, L.F.; Groot, de P.G.; Vissers, J.; Hoefer, I.E.; Pasterkamp, G.; Prins, M.W.J.; Roest, M.

    2013-01-01

    Background : Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming

  20. Crowdsourcing Disease Biomarker Discovery Research: The IP4IC Study.

    Science.gov (United States)

    Chancellor, Michael B; Bartolone, Sarah N; Veerecke, Andrew; Lamb, Laura E

    2018-05-01

    Biomarker discovery is limited by readily assessable, cost efficient human samples available in large numbers that represent the entire heterogeneity of the disease. We developed a novel, active participation crowdsourcing method to determine BP-RS (Bladder Permeability Defect Risk Score). It is based on noninvasive urinary cytokines to discriminate patients with interstitial cystitis/bladder pain syndrome who had Hunner lesions from controls and patients with interstitial cystitis/bladder pain syndrome but without Hunner lesions. We performed a national crowdsourcing study in cooperation with the Interstitial Cystitis Association. Patients answered demographic, symptom severity and urinary frequency questionnaires on a HIPAA (Health Insurance Portability and Accountability Act) compliant website. Urine samples were collected at home, stabilized with a preservative and sent to Beaumont Hospital for analysis. The expression of 3 urinary cytokines was used in a machine learning algorithm to develop BP-RS. The IP4IC study collected a total of 448 urine samples, representing 153 patients (147 females and 6 males) with interstitial cystitis/bladder pain syndrome, of whom 54 (50 females and 4 males) had Hunner lesions. A total of 159 female and 136 male controls also participated, who were age matched. A defined BP-RS was calculated to predict interstitial cystitis/bladder pain syndrome with Hunner lesions or a bladder permeability defect etiology with 89% validity. In this novel participation crowdsourcing study we obtained a large number of urine samples from 46 states, which were collected at home, shipped and stored at room temperature. Using a machine learning algorithm we developed BP-RS to quantify the risk of interstitial cystitis/bladder pain syndrome with Hunner lesions, which is indicative of a bladder permeability defect etiology. To our knowledge BP-RS is the first validated urine biomarker assay for interstitial cystitis/bladder pain syndrome and one of the

  1. Application of bio-marker to study on tumor radiosensitivity

    International Nuclear Information System (INIS)

    Guo Wanfeng; Ding Guirong; Han Liangfu

    2001-01-01

    To definite tumor radiosensitivity is important for applying the schedules of individualization of patient radiotherapy. Many laboratories were carrying on the research which predict the tumor radiosensitivity with one bio-marker or/and multi-bio-marker in various levels. At present has not witnessed the specific bio-marker, but it provides an excellent model for predicting tumor radiosensitivity

  2. Perceived age as clinically useful biomarker of ageing: cohort study

    DEFF Research Database (Denmark)

    Christensen, Kaare; Thinggaard, Mikael; McGue, Matt

    2009-01-01

    OBJECTIVE: To determine whether perceived age correlates with survival and important age related phenotypes. DESIGN: Follow-up study, with survival of twins determined up to January 2008, by which time 675 (37%) had died. SETTING: Population based twin cohort in Denmark. PARTICIPANTS: 20 nurses, 10...... young men, and 11 older women (assessors); 1826 twins aged >or=70. MAIN OUTCOME MEASURES: Assessors: perceived age of twins from photographs. Twins: physical and cognitive tests and molecular biomarker of ageing (leucocyte telomere length). RESULTS: For all three groups of assessors, perceived age...... increased with increasing discordance in perceived age within the twin pair-that is, the bigger the difference in perceived age within the pair, the more likely that the older looking twin died first. Twin analyses suggested that common genetic factors influence both perceived age and survival. Perceived...

  3. Resonance Raman Spectroscopic Evaluation of Skin Carotenoids as a Biomarker of Carotenoid Status for Human Studies

    Science.gov (United States)

    Mayne, Susan T.; Cartmel, Brenda; Scarmo, Stephanie; Jahns, Lisa; Ermakov, Igor V.; Gellermann, Werner

    2013-01-01

    Resonance Raman Spectroscopy (RRS) is a non-invasive method that has been developed to assess carotenoid status in human tissues including human skin in vivo. Skin carotenoid status has been suggested as a promising biomarker for human studies. This manuscript describes research done relevant to the development of this biomarker, including its reproducibility, validity, feasibility for use in field settings, and factors that affect the biomarker such as diet, smoking, and adiposity. Recent studies have evaluated the response of the biomarker to controlled carotenoid interventions, both supplement-based and dietary [e.g., provision of a high-carotenoid fruit and vegetable (F/V)-enriched diet], demonstrating consistent response to intervention. The totality of evidence supports the use of skin carotenoid status as an objective biomarker of F/V intake, although in the cross-sectional setting, diet explains only some of the variation in this biomarker. However, this limitation is also a strength in that skin carotenoids may effectively serve as an integrated biomarker of health, with higher status reflecting greater F/V intake, lack of smoking, and lack of adiposity. Thus, this biomarker holds promise as both a health biomarker and an objective indicator of F/V intake, supporting its further development and utilization for medical and public health purposes. PMID:23823930

  4. Ambient temperature and cardiovascular biomarkers in a repeated-measure study in healthy adults: A novel biomarker index approach.

    Science.gov (United States)

    Wu, Shaowei; Yang, Di; Pan, Lu; Shan, Jiao; Li, Hongyu; Wei, Hongying; Wang, Bin; Huang, Jing; Baccarelli, Andrea A; Shima, Masayuki; Deng, Furong; Guo, Xinbiao

    2017-07-01

    Associations of ambient temperature with cardiovascular morbidity and mortality have been well documented in numerous epidemiological studies, but the underlying pathways remain unclear. We investigated whether systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and endothelial function may be the mechanistic pathways associated with ambient temperature. Forty study participants underwent repeated blood collections for 12 times in Beijing, China in 2010-2011. Ambient temperature and air pollution data were measured in central monitors close to student residences. We created five indices as the sum of weighted biomarker percentiles to represent the overall levels of 15 cardiovascular biomarkers in five pathways (systemic inflammation: hs-CRP, TNF-α and fibrinogen; coagulation: fibrinogen, PAI-1, tPA, vWF and sP-selectin; systemic oxidative stress: Ox-LDL and sCD36: antioxidant activity: EC-SOD and GPX1; and endothelial function: ET-1, E-selectin, ICAM-1 and VCAM-1). We used generalized mixed-effects models to estimate temperature effects controlling for air pollution and other covariates. There were significant decreasing trends in the adjusted means of biomarker indices over the lowest to the highest quartiles of daily temperatures before blood collection. A 10°C decrease at 2-d average daily temperature were associated with increases of 2.5% [95% confidence interval (CI): 0.7, 4.2], 1.6% (95% CI: 0.1, 3.1), 2.7% (95% CI: 0.5, 4.8), 5.5% (95% CI: 3.8, 7.3) and 2.0% (95% CI: 0.3, 3.8) in the indices for systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and endothelial function, respectively. In contrast, the associations between ambient temperature and individual biomarkers had substantial variation in magnitude and strength. The altered cardiovascular biomarker profiles in healthy adults associated with ambient temperature changes may help explain the temperature-related cardiovascular morbidity

  5. Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: Pooling project of 19 cohort studies

    Science.gov (United States)

    The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. This study sought to evaluate biomarkers of seafood-derived eicosapentaenoic acid ...

  6. 76 FR 82306 - Draft Guidance for Industry on Use of Histology in Biomarker Qualification Studies; Availability

    Science.gov (United States)

    2011-12-30

    ...] Draft Guidance for Industry on Use of Histology in Biomarker Qualification Studies; Availability AGENCY... announcing the availability of a draft guidance for industry entitled ``Use of Histology in Biomarker... studies for which histology is a reference standard. This guidance discusses the processes that should be...

  7. 78 FR 36753 - North Atlantic Coast Comprehensive Study

    Science.gov (United States)

    2013-06-19

    ... Disaster Relief Appropriations Act, Public Law 113-2, are to (1) reduce flood risk to vulnerable coastal... measure. The Comprehensive Study will also include storm suite modeling, coastal GIS analyses, economic...

  8. Comprehensive embryo testing. Experts' opinions regarding future directions: an expert panel study on comprehensive embryo testing.

    Science.gov (United States)

    Hens, Kristien; Dondorp, Wybo J; Geraedts, Joep P M; de Wert, Guido M

    2013-05-01

    four Western Europe countries. As willingness to participate in this study may be connected with expectations regarding the pace and direction of future developments, selection bias cannot be excluded. The introduction of comprehensive screening techniques in embryo testing calls for further ethical reflection that is grounded in empirical work. Specifically, there is a need for studies querying the opinions of infertile couples undergoing IVF/PGS regarding the desirability of embryo screening beyond aneuploidy. This research was supported by the CSG, Centre for Society and Life Sciences (project number: 70.1.074). The authors declare no conflict of interest. N/A.

  9. Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study

    NARCIS (Netherlands)

    Daan, Nadine M P; Koster, Maria P H; de Wilde, Marlieke A; Dalmeijer, Gerdien W; Evelein, Annemieke M V; Fauser, Bart C J M; de Jager, Wilco

    2016-01-01

    OBJECTIVE: To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. DESIGN: Cross-sectional comparison of serum biomarkers. SETTING: University Medical Center Utrecht. PATIENTS: Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n

  10. ACE inhibition with perindopril and biomarkers of atherosclerosis and thrombosis : Results from the PERTINENT study

    NARCIS (Netherlands)

    Ceconi, C.; Fox, K.M.; Remme, W.J.; Simoons, M.L.; Deckers, J.W.; Bertrand, M.; Parrinello, G.; Kluft, C.; Blann, A.; Cokkinos, D.; Ferrari, R.

    2009-01-01

    The PERTINENT study measured biomarkers of atherosclerosis and thrombosis in a stable coronary artery disease population from EUROPA receiving ACE inhibition with perindopril 8 mg/day or placebo. Biomarkers of inflammation, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor-alpha

  11. Biomarker kinetics in the prediction of VAP diagnosis: results from the BioVAP study

    NARCIS (Netherlands)

    Póvoa, Pedro; Martin-Loeches, Ignacio; Ramirez, Paula; Bos, Lieuwe D.; Esperatti, Mariano; Silvestre, Joana; Gili, Gisela; Goma, Gema; Berlanga, Eugenio; Espasa, Mateu; Gonçalves, Elsa; Torres, Antoni; Artigas, Antonio

    2016-01-01

    Prediction of diagnosis of ventilator-associated pneumonia (VAP) remains difficult. Our aim was to assess the value of biomarker kinetics in VAP prediction. We performed a prospective, multicenter, observational study to evaluate predictive accuracy of biomarker kinetics, namely C-reactive protein

  12. Multimodal lung cancer screening using the ITALUNG biomarker panel and low dose computed tomography. Results of the ITALUNG biomarker study.

    Science.gov (United States)

    Carozzi, Francesca Maria; Bisanzi, Simonetta; Carrozzi, Laura; Falaschi, Fabio; Lopes Pegna, Andrea; Mascalchi, Mario; Picozzi, Giulia; Peluso, Marco; Sani, Cristina; Greco, Luana; Ocello, Cristina; Paci, Eugenio

    2017-07-01

    Asymptomatic high-risk subjects, randomized in the intervention arm of the ITALUNG trial (1,406 screened for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1,356), in which samples of blood and sputum were analyzed for plasma DNA quantification (cut off 5 ng/ml), loss of heterozygosity and microsatellite instability. The ITALUNG biomarker panel (IBP) was considered positive if at least one of the two biomarkers included in the panel was positive. Subjects with and without lung cancer diagnosis at the end of the screening cycle with LDCT (n = 517) were evaluated. Out of 18 baseline screen detected lung cancer cases, 17 were IBP positive (94%). Repeat screen-detected lung cancer cases were 18 and 12 of them positive at baseline IBP test (66%). Interval cancer cases (2-years) and biomarker tests after a suspect Non Calcific Nodule follow-up were investigated. The single test versus multimodal screening measures of accuracy were compared in a simulation within the screened ITALUNG intervention arm, considering screen-detected and interval cancer cases. Sensitivity was 90% at baseline screening. Specificity was 71 and 61% for LDCT and IBP as baseline single test, and improved at 89% with multimodal, combined screening. The positive predictive value was 4.3% for LDCT at baseline and 10.6% for multimodal screening. Multimodal screening could improve the screening efficiency at baseline and strategies for future implementation are discussed. If IBP was used as primary screening test, the LDCT burden might decrease of about 60%. © 2017 UICC.

  13. Comprehensive Quantitative Profiling of Tau and Phosphorylated Tau Peptides in Cerebrospinal Fluid by Mass Spectrometry Provides New Biomarker Candidates.

    Science.gov (United States)

    Russell, Claire L; Mitra, Vikram; Hansson, Karl; Blennow, Kaj; Gobom, Johan; Zetterberg, Henrik; Hiltunen, Mikko; Ward, Malcolm; Pike, Ian

    2017-01-01

    Aberrant tau phosphorylation is a hallmark in Alzheimer's disease (AD), believed to promote formation of paired helical filaments, the main constituent of neurofibrillary tangles in the brain. While cerebrospinal fluid (CSF) levels of total tau and tau phosphorylated at threonine residue 181 (pThr181) are established core biomarkers for AD, the value of alternative phosphorylation sites, which may have more direct relevance to pathology, for early diagnosis is not yet known, largely due to their low levels in CSF and lack of standardized detection methods. To overcome sensitivity limitations for analysis of phosphorylated tau in CSF, we have applied an innovative mass spectrometry (MS) workflow, TMTcalibratortrademark, to enrich and enhance the detection of phosphoproteome components of AD brain tissue in CSF, and enable the quantitation of these analytes. We aimed to identify which tau species present in the AD brain are also detectable in CSF and which, if any, are differentially regulated with disease. Over 75% coverage of full-length (2N4R) tau was detected in the CSF with 47 phosphopeptides covering 31 different phosphorylation sites. Of these, 11 phosphopeptides were upregulated by at least 40%, along with an overall increase in tau levels in the CSF of AD patients relative to controls. Use of the TMTcalibratortrademark workflow dramatically improved our ability to detect tau-derived peptides that are directly related to human AD pathology. Further validation of regulated tau peptides as early biomarkers of AD is warranted and is currently being undertaken.

  14. Readers Theatre plus Comprehension and Word Study

    Science.gov (United States)

    Young, Chase; Stokes, Faida; Rasinski, Timothy

    2017-01-01

    Readers Theatre has been used to introduce critical issues, promote fluency among English learners and non-English learners, teach vocabulary, and integrate content in the classroom. Previous studies of Readers Theatre application have demonstrated an increase in student reading fluency, motivation, and confidence. The focus of this systemic…

  15. Heritability of Biomarkers of Oxidized Lipoproteins: Twin Pair Study.

    Science.gov (United States)

    Rao, Fangwen; Schork, Andrew J; Maihofer, Adam X; Nievergelt, Caroline M; Marcovina, Santica M; Miller, Elizabeth R; Witztum, Joseph L; O'Connor, Daniel T; Tsimikas, Sotirios

    2015-07-01

    To determine whether biomarkers of oxidized lipoproteins are genetically determined. Lipoprotein(a) (Lp[a]) is a heritable risk factor and carrier of oxidized phospholipids (OxPL). We measured oxidized phospholipids on apolipoprotein B-containing lipoproteins (OxPL-apoB), Lp(a), IgG, and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes in 386 monozygotic and dizygotic twins to estimate trait heritability (h(2)) and determine specific genetic effects among traits. A genome-wide linkage study followed by genetic association was performed. The h(2) (scale: 0-1) for Lp(a) was 0.91±0.01 and for OxPL-apoB 0.87±0.02, which were higher than physiological, inflammatory, or lipid traits. h(2) of IgM malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes were 0.69±0.04, 0.67±0.05, and 0.80±0.03, respectively, and for IgG malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes 0.62±0.05, 0.52±0.06, and 0.53±0.06, respectively. There was an inverse correlation between the major apo(a) isoform and OxPL-apoB (R=-0.49; Plipoprotein and copper oxidized low-density lipoprotein, and apoB-immune complexes. Sib-pair genetic linkage of the Lp(a) trait revealed that single nucleotide polymorphism rs10455872 was significantly associated with OxPL-apoB after adjusting for Lp(a). OxPL-apoB and other biomarkers of oxidized lipoproteins are highly heritable cardiovascular risk factors that suggest novel genetic origins of atherothrombosis. © 2015 American Heart Association, Inc.

  16. Biomarkers study in rainbow trout exposed to industrially contaminated groundwater

    Directory of Open Access Journals (Sweden)

    Nadjet Benchalgo

    2014-03-01

    Full Text Available The spill of liquid industrial waste from chemical and petrochemical industries in Mercier lagoons located 20 km south of Montreal, Quebec, caused a major groundwater contamination by industrial contaminants. The aim of this study was to investigate the toxic effects of Mercier groundwater, following 4 and 14 days of exposure to graded concentrations from three wells at increasing distances 1.2, 2.7 and 5.4 km from the source of contamination. Rainbow trout were examined for several biomarkers of defense [ethoxyresorufin O-deethylase (EROD and gluthatione S-transferase (GST activities] and those of tissue damage [lipid peroxidation (LPO and DNA strand breaks]. The results showed that EROD activity was significantly enhanced in hepatic tissue at 1.2 and 5.4 km, whereas inhibition in activity was observed in group at 2.7 km. Therefore, GST activity was significantly increased at 3.1% concentration for the 2.7 km well. No change in LPO was observed. However, a significant induction of DNA strand breaks in liver was obtained at each distance. In conclusion, the data suggest that the release of these contaminants in groundwater leads to increased biotransformation for coplanar aromatic hydrocarbons and DNA damage in groundwater.

  17. A comprehensive study of methyl decanoate pyrolysis

    International Nuclear Information System (INIS)

    Pyl, Steven P.; Van Geem, Kevin M.; Puimège, Philip; Sabbe, Maarten K.; Reyniers, Marie-Françoise; Marin, Guy B.

    2012-01-01

    The thermal decomposition of methyl decanoate (MD) was studied in a bench-scale pyrolysis set-up equipped with a dedicated on-line analysis section including a GC × GC-FID/(TOF-MS). This analysis section enables quantitative and qualitative on-line analyses of the entire reactor effluent with high level of detail including measurement of formaldehyde and water. The reactor temperature was varied from 873 K to 1123 K at a fixed pressure of 1.7 bar and a fixed residence time of 0.5 s, for both high (10mol N 2 /mol MD ) and low (0.6mol N 2 /mol MD ) nitrogen dilution. Thus covering a wide conversion range in both dilution regimes. In these experiments, significant amounts of large linear olefins and unsaturated esters were observed at lower temperatures, the amounts of which decreased at higher temperatures in favor of permanent gasses (CO, CO 2 , CH 4 ) and light olefins. At the highest temperatures more than 5 wt% of mono-aromatic and poly-aromatic components were observed. The acquired dataset was used to validate 3 recently published microkinetic models which were developed to model oxidation and/or pyrolysis of methyl decanoate. The results showed that these models accurately predict the product distribution, although important discrepancies were observed for some major products such as certain unsaturated esters, CO 2 and H 2 O. Reaction path analyses and CBS-QB3 quantum-chemical calculations are presented and discussed in order to explain the observed differences. -- Highlights: ► New extensive experimental dataset for the pyrolysis of methyl decanoate in a tubular reactor. ► A dedicated separation section including on-line GC × GC allows to obtain quantitative data for over 150 components. ► High level ab-initio calculations for important reactions of the methyl decanoate decomposition. ► Identification of missing reactions/reaction families/inaccurate kinetics in the presently available kinetic models.

  18. Genomic Biomarkers for Personalized Medicine: Development and Validation in Clinical Studies

    Directory of Open Access Journals (Sweden)

    Shigeyuki Matsui

    2013-01-01

    Full Text Available The establishment of high-throughput technologies has brought substantial advances to our understanding of the biology of many diseases at the molecular level and increasing expectations on the development of innovative molecularly targeted treatments and molecular biomarkers or diagnostic tests in the context of clinical studies. In this review article, we position the two critical statistical analyses of high-dimensional genomic data, gene screening and prediction, in the framework of development and validation of genomic biomarkers or signatures, through taking into consideration the possible different strategies for developing genomic signatures. A wide variety of biomarker-based clinical trial designs to assess clinical utility of a biomarker or a new treatment with a companion biomarker are also discussed.

  19. Follow-up study on reading comprehension in Down's syndrome: the role of reading skills and listening comprehension.

    Science.gov (United States)

    Roch, Maja; Florit, Elena; Levorato, Chiara

    2011-01-01

    According to the 'Simple View of Reading', reading comprehension requires some abilities such as reading skill and listening comprehension. Individuals with Down's syndrome show relative strengths in reading skills, mainly in word recognition, where they attain a reading age of about 7-8 years. Compared with word recognition, their reading comprehension is usually delayed by at least 6 months. Poor reading comprehension is paralleled by weak listening comprehension. It is claimed that poor listening comprehension might constrain the development of reading comprehension and, therefore, be a cause for the asynchrony between reading skills and reading comprehension. A follow-up study was carried out in order to analyse the improvements in reading skills, listening and reading text comprehension, and to support the hypothesis of a causal relationship between listening and reading comprehension. Ten children and adolescents with Down's syndrome, aged between 11 years 3 months and 19 years 10 months, were assessed twice over a one-year period as to their reading skills, listening and reading text comprehension. Three main findings emerged: (1) reading skills, on the one hand, and comprehension (both listening and reading), on the other hand, are independent; (2) reading comprehension development is determined mainly by listening comprehension, which in the present study proved to be very poor; and (3) an improvement after a one-year period, even though limited, occurred for all examined abilities except for listening comprehension. The results are discussed in the light of the theoretical framework of the 'Simple View of Reading' and of their relevance for practical and educational issues. © 2011 Royal College of Speech & Language Therapists.

  20. CHURCHILL COUNTY, NEVADA ARSENIC STUDY: WATER CONSUMPTION AND EXPOSURE BIOMARKERS

    Science.gov (United States)

    The US Environmental Protection Agency is required to reevaluate the Maximum Contaminant Level (MCL) for arsenic in 2006. To provide data for reducing uncertainties in assessing health risks associated with exposure to low levels (<200 g/l) of arsenic, a large scale biomarker st...

  1. Molecular biomarkers for the study of childhood leukemia

    International Nuclear Information System (INIS)

    Smith, Martyn T.; McHale, Cliona M.; Wiemels, Joseph L.; Zhang, Luoping; Wiencke, John K.; Zheng, Shichun; Gunn, Laura; Skibola, Christine F.; Ma, Xiaomei; Buffler, Patricia A.

    2005-01-01

    Various specific chromosome rearrangements, including t(8;21), t(15;17), and inv(16), are found in acute myeloid leukemia (AML) and in childhood acute lymphocytic leukemia (ALL), t(12;21) and t(1;19) are common. We sequenced the translocation breakpoints of 56 patients with childhood ALL or AML harboring t(12;21), t(8;21), t(15;17), inv(16), and t(1;19), and demonstrated, with the notable exception of t(1;19), that these rearrangements are commonly detected in the neonatal blood spots (Guthrie cards) of the cases. These findings show that most childhood leukemias begin before birth and that maternal and perinatal exposures such as chemical and infectious agents are likely to be critical. Indeed, we have reported that exposure to indoor pesticides during pregnancy and the first year of life raises leukemia risk, but that later exposures do not. We have also examined aberrant gene methylation in different cytogenetic subgroups and have found striking differences between them, suggesting that epigenetic events are also important in the development of some forms of childhood leukemia. Further, at least two studies now show that the inactivating NAD(P)H:quinone acceptor oxidoreductase (NQO1) C609T polymorphism is positively associated with leukemias arising in the first 1-2 years of life and polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have been associated with adult and childhood ALL. Thus, low folate intake and compounds that are detoxified by NQO1 may be important in elevating leukemia risk in children. Finally, we are exploring the use of proteomics to subclassify leukemia, because cytogenetic analysis is costly and time-consuming. Several proteins have been identified that may serve as useful biomarkers for rapidly identifying different forms of childhood leukemia

  2. Serum miRNAs as Biomarkers for the Diagnosis and Prognosis of Thyroid Cancer: A Comprehensive Review of the Literature.

    Science.gov (United States)

    Mahmoudian-Sani, Mohammad-Reza; Mehri-Ghahfarrokhi, Ameneh; Asadi-Samani, Majid; Mobini, Gholam-Reza

    2017-07-01

    Thyroid cancer is the most common endocrine malignancy and accounts for 1% of cancers. In recent years, there has been much interest in the feasibility of using miRNAs or miRNA panels as biomarkers for the diagnosis of thyroid cancer. miRNAs are noncoding RNAs with 21-23 nucleotides that are highly conserved during evolution. They have been proposed as regulators of gene expression, apoptosis, cancer, and cell growth and differentiation. The Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO), and Web of Science were searched. The serum level of miRNAs (miRNA-375, 34a, 145b, 221, 222, 155, Let-7, 181b) can be used as molecular markers for the diagnosis and prognosis of thyroid cancer in the serum samples of patients with thyroid glands. Given that most common methods for the screening of thyroid cancer cannot detect the disease in its early stages, identifying miRNAs that are released in the bloodstream during the gradual progression of the disease is considered a key method in the early diagnosis of thyroid cancers.

  3. Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.

    Science.gov (United States)

    Wang, Thomas J; Wollert, Kai C; Larson, Martin G; Coglianese, Erin; McCabe, Elizabeth L; Cheng, Susan; Ho, Jennifer E; Fradley, Michael G; Ghorbani, Anahita; Xanthakis, Vanessa; Kempf, Tibor; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Januzzi, James L

    2012-09-25

    Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3428 participants (mean age, 59 years; 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a "multimarker" score composed of the 3 biomarkers in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each end point (Pstatistic (P=0.005 or lower) and net reclassification improvement (P=0.001 or lower). Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.

  4. Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study

    DEFF Research Database (Denmark)

    Silkoff, P E; Strambu, I; Laviolette, M

    2015-01-01

    BACKGROUND: Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This re...

  5. Comprehensive Stuttering Treatment for Adolescents: A Case Study.

    Science.gov (United States)

    Coleman, Craig E

    2018-01-09

    This article will focus on a hypothetical case study to highlight comprehensive assessment and treatment for adolescent children who stutter. Assessment and treatment are laid out with a literature review utilizing the components of the International Classification of Functioning, Disability and Health model. Specific assessment and treatment strategies and approaches are discussed. Using the International Classification of Functioning, Disability and Health model can help guide clinicians through the assessment and treatment process to ensure that all areas of stuttering are considered. Comprehensive assessment and treatment helps clinicians address all relevant elements of a stuttering disorder, rather than focusing exclusively on reducing speech disruptions.

  6. 78 FR 61844 - North Atlantic Coast Comprehensive Study

    Science.gov (United States)

    2013-10-04

    ...: The U.S. Army Corps of Engineers (USACE) is requesting peer reviewed information that would be useful in the preparation of the North Atlantic Coast Comprehensive Study (Hurricane Sandy). The USACE is... information by electronic mail to: [email protected] . Please include your name and contact information in...

  7. Comprehensive Stuttering Treatment or Adolescents: A Case Study

    Science.gov (United States)

    Coleman, Craig E.

    2018-01-01

    Purpose: This article will focus on a hypothetical case study to highlight comprehensive assessment and treatment for adolescent children who stutter. Method: Assessment and treatment are laid out with a literature review utilizing the components of the International Classification of Functioning, Disability and Health model. Specific assessment…

  8. Ciclo Basico Polivalente (Basic Comprehensive Courses of Study).

    Science.gov (United States)

    Boletin del Centro Nacional de Documentacion e Informacion Educativa, 1970

    1970-01-01

    This article discusses the creation of comprehensive secondary schools in Argentina to meet the diversified goals of the population in any given geographical region. The plan described here provides for the creation of several basic-study cycles within one school so that students may pursue courses in commercial, technical, and academic fields.…

  9. Pharmacogenomic Biomarkers

    Directory of Open Access Journals (Sweden)

    Sandra C. Kirkwood

    2002-01-01

    Full Text Available Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

  10. Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Rosario Lopez-Rodriguez

    Full Text Available Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA, given their variable response to TNF inhibitors (TNFi. However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.

  11. BIOMarkers for occupational diesel exhaust exposure monitoring (BIOMODEM) - a study in underground mining

    DEFF Research Database (Denmark)

    Scheepers, P.T.J.; Coggon, D.; Knudsen, Lisbeth E.

    2002-01-01

    Methods for the assessment of exposures to diesel exhaust were evaluated, including various biomarkers of internal exposure and early biological effects. The impact of possible biomarkers of susceptibility was also explored. Underground workers (drivers of diesel-powered excavators) at an oil sha...... bulky DNA adducts determined by 32P-postlabelling, or in DNA damage. The study indicated that smoking, diet and residential indoor air pollution are important non-occupational factors to consider when interpreting biomonitoring results....

  12. Children's exposure to environmental pollutants and biomarkers of genetic damage. II. Results of a comprehensive literature search and meta-analysis

    DEFF Research Database (Denmark)

    Neri, Monica; Ugolini, Donatella; Bonassi, Stefano

    2005-01-01

    The present review is based on findings from 178 publications retrieved through an extensive search of the MedLine/PubMed database for a 25 years time period (1980-2004) and 10 manually identified papers. Among the cytogenetic biomarkers that are frequently used in field studies, chromosome...... pollutants, soil and drinking water contaminants, mostly increased CA and, to a lesser extent, MN levels in children. The effect of exposure to airborne urban pollutants was consistently reported by field studies measuring DNA, albumin and hemoglobin adducts. Prenatal (in utero) and postnatal exposure...

  13. Strategies to design clinical studies to identify predictive biomarkers in cancer research.

    Science.gov (United States)

    Perez-Gracia, Jose Luis; Sanmamed, Miguel F; Bosch, Ana; Patiño-Garcia, Ana; Schalper, Kurt A; Segura, Victor; Bellmunt, Joaquim; Tabernero, Josep; Sweeney, Christopher J; Choueiri, Toni K; Martín, Miguel; Fusco, Juan Pablo; Rodriguez-Ruiz, Maria Esperanza; Calvo, Alfonso; Prior, Celia; Paz-Ares, Luis; Pio, Ruben; Gonzalez-Billalabeitia, Enrique; Gonzalez Hernandez, Alvaro; Páez, David; Piulats, Jose María; Gurpide, Alfonso; Andueza, Mapi; de Velasco, Guillermo; Pazo, Roberto; Grande, Enrique; Nicolas, Pilar; Abad-Santos, Francisco; Garcia-Donas, Jesus; Castellano, Daniel; Pajares, María J; Suarez, Cristina; Colomer, Ramon; Montuenga, Luis M; Melero, Ignacio

    2017-02-01

    The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework-the DESIGN guidelines-to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Biomarker Discovery in Human Prostate Cancer: an Update in Metabolomics Studies

    Directory of Open Access Journals (Sweden)

    Ana Rita Lima

    2016-08-01

    Full Text Available Prostate cancer (PCa is the most frequently diagnosed cancer and the second leading cause of cancer death among men in Western countries. Current screening techniques are based on the measurement of serum prostate specific antigen (PSA levels and digital rectal examination. A decisive diagnosis of PCa is based on prostate biopsies; however, this approach can lead to false-positive and false-negative results. Therefore, it is important to discover new biomarkers for the diagnosis of PCa, preferably noninvasive ones. Metabolomics is an approach that allows the analysis of the entire metabolic profile of a biological system. As neoplastic cells have a unique metabolic phenotype related to cancer development and progression, the identification of dysfunctional metabolic pathways using metabolomics can be used to discover cancer biomarkers and therapeutic targets. In this study, we review several metabolomics studies performed in prostatic fluid, blood plasma/serum, urine, tissues and immortalized cultured cell lines with the objective of discovering alterations in the metabolic phenotype of PCa and thus discovering new biomarkers for the diagnosis of PCa. Encouraging results using metabolomics have been reported for PCa, with sarcosine being one of the most promising biomarkers identified to date. However, the use of sarcosine as a PCa biomarker in the clinic remains a controversial issue within the scientific community. Beyond sarcosine, other metabolites are considered to be biomarkers for PCa, but they still need clinical validation. Despite the lack of metabolomics biomarkers reaching clinical practice, metabolomics proved to be a powerful tool in the discovery of new biomarkers for PCa detection.

  15. The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort

    Science.gov (United States)

    Goldman, Jennifer G.; Alcalay, Roy N.; Xie, Tao; Tuite, Paul; Henchcliffe, Claire; Hogarth, Penelope; Amara, Amy W.; Frank, Samuel; Rudolph, Alice; Casaceli, Cynthia; Andrews, Howard; Gwinn, Katrina; Sutherland, Margaret; Kopil, Catherine; Vincent, Lona; Frasier, Mark

    2016-01-01

    ABSTRACT Background Identifying PD‐specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, variability of collection protocols, and focus on de novo, unmedicated patients. Thus, a platform for biomarker discovery and validation in well‐characterized, clinically typical, moderate to advanced PD cohorts is critically needed. Methods BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease) is a cross‐sectional, multicenter biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva, and urine samples from 118 moderate to advanced PD and 88 healthy control subjects. Inclusion criteria were designed to maximize diagnostic specificity by selecting participants with clinically typical PD symptoms, and clinical data and biospecimen collection utilized standardized procedures to minimize variability across sites. Results We present the study methodology and data on the cohort's clinical characteristics. Motor scores and biospecimen samples including plasma are available for practically defined off and on states and thus enable testing the effects of PD medications on biomarkers. Other biospecimens are available from off state PD assessments and from controls. Conclusion Our cohort provides a valuable resource for biomarker discovery and validation in PD. Clinical data and biospecimens, available through The Michael J. Fox Foundation for Parkinson's Research and the National Institute of Neurological Disorders and Stroke, can serve as a platform for discovering biomarkers in clinically typical PD and comparisons across PD's broad and heterogeneous spectrum. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:27113479

  16. Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu [Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Wang, Qiao; Cheng, Jun [Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Zhang, Jingshun; Xu, Jiaojiao [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang (China); Ren, Yiping, E-mail: renyiping@263.net [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang (China)

    2015-09-24

    Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1–0.3 ng/mL and 0.4–1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%–105.4%, 98.2%–114.0% and 92.2%–108.9%, respectively. Acceptable within-laboratory reproducibility (RSD < 7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive

  17. Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry

    International Nuclear Information System (INIS)

    Zhang, Yu; Wang, Qiao; Cheng, Jun; Zhang, Jingshun; Xu, Jiaojiao; Ren, Yiping

    2015-01-01

    Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1–0.3 ng/mL and 0.4–1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%–105.4%, 98.2%–114.0% and 92.2%–108.9%, respectively. Acceptable within-laboratory reproducibility (RSD < 7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive

  18. NABIR Assessment Element, Expanded Rapid, Comprehensive, Lipid Biomarker Analysis for Subsurface, Community Composition and Nutritional/Physiological Status as Monitors of Remediation and Detoxification Effectiveness

    International Nuclear Information System (INIS)

    David C. White

    2005-01-01

    NABIR funding at the University of Tennessee Center for Biomarker Analysis (CBA) has led to several key contributions to the investigation of bioremediation of metals and radionuclides. This lab has played an integral part in assessing microbial communities at the field scale at the ORNL FRC (Istok et al., 2004) and two UMTRA sites (Anderson et al., 2003, Chang et al., 2001). Our work over the period of the grant has resulted in 42-peer reviewed publications, 62 presentations (14 of which were international), and one patent pending. Currently CBA has 2 papers in press. The main objectives relating to the field portion of this program were to provide comprehensive biomarker analysis for NABIR collaborators to enhance the understanding of microbial geo-bioprocesses involved in the effective immobilization of metals (We have worked with and published or currently are publishing with 10 groups of NAIBR investigators). The laboratory portion of our research centered on methods development and has led to three major innovations that could result in a systematic way of evaluating sites for potential bioremediation. The first of these is the development of an in situ sampling device (Peacock et al., 2004, Anderson et al., 2003, Istok et al., 2004) for the collection and concentration of microbial biomass. The second is the development of expanded lipid analysis based on the significantly greater sensitivity and selectivity of the LC/MS/MS that allows the analysis of respiratory quinones, diglycerides, sterols, intact phospholipids, poly-hydroxyalkonates, and potentially archaeol, and caldarchaeols from archea. These new analyses are accomplished more rapidly and with increased sensitivities and resolution than in the past (Lytle et al., 2000a, 2000b, 2001a, Geyer et al., 2004). The third advance is the coupling of lipid analysis with 13C enrichment experiments (Lytle et al., 2001b, Geyer et al. 2005). With this technique it is now possible to follow the active portion of

  19. Alarmins as biomarkers of gastrointestinal surgical injury - a pilot study.

    Science.gov (United States)

    Maca, Jan; Holub, Michal; Bursa, Filip; Ihnat, Peter; Reimer, Petr; Svagera, Zdenek; Burda, Michal; Sevcik, Pavel

    2018-02-01

    The dysregulation of inflammatory response to surgical injury affects outcomes. Alarmins, the earliest bioactive substances from damaged cells, play a crucial role in initiating the inflammation. We analyzed serum levels of alarmins (S100A8, S100A12, high mobility group box, and heat shock protein 70) after major abdominal surgery (MAS) in surgical (S) (n = 82) and nonsurgical (NS) groups (n = 35). The main objective was determining a role of selected alarmins in host response to MAS. The secondary objectives were (i) evaluation of the relationship among alarmins and selected biomarkers (C-reactive protein, interleukin-6), (ii) influence of the place of gastrointestinal resection, and (iii) role of alarmins in MAS for cancer. Except for HMGB1, the levels of all alarmins were higher in the S group compared with the NS group. In the S group, positive correlations were found between S100A8 and both IL-6 and CRP. Additionally, the S100A8 level was higher (p < 0.01) in patients who underwent upper gastrointestinal tract (GIT) surgery compared to middle and lower GIT resections. Alarmins levels did not differ between cancer and noncancer patients. MAS is able to elicit increase in alarmin levels. S100A8 can be considered a potential biomarker of surgical injury, especially in the upper part of the GIT. © 2018 APMIS. Published by John Wiley & Sons Ltd.

  20. Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome-a prospective multicentre biomarker study conducted in the Netherlands.

    Science.gov (United States)

    Oemrawsingh, Rohit M; Akkerhuis, K Martijn; Umans, Victor A; Kietselaer, Bas; Schotborgh, Carl; Ronner, Eelko; Lenderink, Timo; Liem, Anho; Haitsma, David; van der Harst, Pim; Asselbergs, Folkert W; Maas, Arthur; Oude Ophuis, Anton J; Ilmer, Ben; Dijkgraaf, Rene; de Winter, Robbert-Jan; The, S Hong Kie; Wardeh, Alexander J; Hermans, Walter; Cramer, Etienne; van Schaik, Ron H; Hoefer, Imo E; Doevendans, Pieter A; Simoons, Maarten L; Boersma, Eric

    2016-12-23

    Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such 'vulnerable periods'. BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate 'vulnerable periods' during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case-cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS. Follow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should

  1. The Australian biomarker, imaging and lifestyle study: phase 1 amyloid imaging results

    International Nuclear Information System (INIS)

    Rowe, C. C.; Pike, K.; Villemagne, V. L.; Morandeau, L.; Masters, C. L.; Ames, D.

    2009-01-01

    Full text:Background: Phase 1 of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing, a three-year prospective longitudinal study recruiting 1,112 volunteers from a cross-section of Australia's elderly population, concluded with more than a quarter of the participants undergoing PiB-PET. Methods: 287 participants received PiB PET scans: 177 Healthy controls (HC); 57 Mild Cognitive Impairment (MCI) subjects; and 53 mild Alzheimer's disease (AD) patients. HC were further classified according to their subjective memory complaints and genetic predisposition. All participants underwent a comprehensive neuropsychological examination, a 3D T1 MP-RAGE and T2 FSE MR, and a PiB-PET scan. Regional and global cortical SUVR were calculated using the cerebellar cortex as reference region. A SUVR cut-off of 1.40 was used to define PiB scans as normal or abnormal. Results: Cortical PIB binding was markedly elevated in all AD patients except one. MCI subjects presented either an AD-like (63%) or normal pattern. Cortical PiB retention was abnormal in 34% of HC and the prevalence increased with age. HC with subjective memory complaints carrying an ApoE4 allele had significantly higher A burdens than non ApoE4 carriers. Conclusions: Phase 1 of the AIBL study has set the foundations for the longitudinal assessment of A burden in HC, MCI and AD. This wil assist the development of techniques for early detection of AD providing a cohort suitable for targeted early intervention studies.

  2. Reconstructing exposures from biomarkers using exposure-pharmacokinetic modeling--A case study with carbaryl.

    Science.gov (United States)

    Brown, Kathleen; Phillips, Martin; Grulke, Christopher; Yoon, Miyoung; Young, Bruce; McDougall, Robin; Leonard, Jeremy; Lu, Jingtao; Lefew, William; Tan, Yu-Mei

    2015-12-01

    Sources of uncertainty involved in exposure reconstruction for short half-life chemicals were characterized using computational models that link external exposures to biomarkers. Using carbaryl as an example, an exposure model, the Cumulative and Aggregate Risk Evaluation System (CARES), was used to generate time-concentration profiles for 500 virtual individuals exposed to carbaryl. These exposure profiles were used as inputs into a physiologically based pharmacokinetic (PBPK) model to predict urinary biomarker concentrations. These matching dietary intake levels and biomarker concentrations were used to (1) compare three reverse dosimetry approaches based on their ability to predict the central tendency of the intake dose distribution; and (2) identify parameters necessary for a more accurate exposure reconstruction. This study illustrates the trade-offs between using non-iterative reverse dosimetry methods that are fast, less precise and iterative methods that are slow, more precise. This study also intimates the necessity of including urine flow rate and elapsed time between last dose and urine sampling as part of the biomarker sampling collection for better interpretation of urinary biomarker data of short biological half-life chemicals. Resolution of these critical data gaps can allow exposure reconstruction methods to better predict population-level intake doses from large biomonitoring studies. Published by Elsevier Inc.

  3. Mycotoxin exposure in rural residents in northern Nigeria: a pilot study using multi-urinary biomarkers.

    Science.gov (United States)

    Ezekiel, Chibundu N; Warth, Benedikt; Ogara, Isaac M; Abia, Wilfred A; Ezekiel, Victoria C; Atehnkeng, Joseph; Sulyok, Michael; Turner, Paul C; Tayo, Grace O; Krska, Rudolf; Bandyopadhyay, Ranajit

    2014-05-01

    A pilot, cross-sectional, correlational study was conducted in eight rural communities in northern Nigeria to investigate mycotoxin exposures in 120 volunteers (19 children, 20 adolescents and 81 adults) using a modern LC-MS/MS based multi-biomarker approach. First morning urine samples were analyzed and urinary biomarker levels correlated with mycotoxin levels in foods consumed the day before urine collection. A total of eight analytes were detected in 61/120 (50.8%) of studied urine samples, with ochratoxin A, aflatoxin M1 and fumonisin B1 being the most frequently occurring biomarkers of exposure. These mycotoxin biomarkers were present in samples from all age categories, suggestive of chronic (lifetime) exposures. Rough estimates of mycotoxin intake suggested some exposures were higher than the tolerable daily intake. Overall, rural consumer populations from Nasarawa were more exposed to several mixtures of mycotoxins in their diets relative to those from Kaduna as shown by food and urine biomarker data. This study has shown that mycotoxin co-exposure may be a major public health challenge in rural Nigeria; this calls for urgent intervention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. A comprehensive study of sparse codes on abnormality detection

    DEFF Research Database (Denmark)

    Ren, Huamin; Pan, Hong; Olsen, Søren Ingvor

    2017-01-01

    Sparse representation has been applied successfully in abnor-mal event detection, in which the baseline is to learn a dic-tionary accompanied by sparse codes. While much empha-sis is put on discriminative dictionary construction, there areno comparative studies of sparse codes regarding abnormal-ity...... detection. We comprehensively study two types of sparsecodes solutions - greedy algorithms and convex L1-norm so-lutions - and their impact on abnormality detection perfor-mance. We also propose our framework of combining sparsecodes with different detection methods. Our comparative ex-periments are carried...

  5. A review of the studies on listening comprehension in the second language

    OpenAIRE

    Fukuda, Michiko

    2003-01-01

    Few studies have been done on the listening comprehension processing, especially in second language. However, recent studies show that listening comprehension is considered as an active and cognitive process. This paper overviews studies on listening comprehension in the second language by presenting some models of listening comprehension processing. Then, listening comprehension was studied from cognitive psychology and educational point of view. Finally, the direction of future researches o...

  6. Candidate Biomarkers in Children with Autism Spectrum Disorder: A Review of MRI Studies

    Institute of Scientific and Technical Information of China (English)

    Dongyun Li; Hans-Otto Karnath; Xiu Xu

    2017-01-01

    Searching for effective biomarkers is one of the most challenging tasks in the research field of Autism Spectrum Disorder (ASD).Magnetic resonance imaging (MRI) provides a non-invasive and powerful tool for investigating changes in the structure,function,maturation,connectivity,and metabolism of the brain of children with ASD.Here,we review the more recent MRI studies in young children with ASD,aiming to provide candidate biomarkers for the diagnosis of childhood ASD.The review covers structural imaging methods,diffusion tensor imaging,resting-state functional MRI,and magnetic reso nance spectroscopy.Future advances in neuroimaging techniques,as well as cross-disciplinary studies and largescale collaborations will be needed for an integrated approach linking neuroimaging,genetics,and phenotypic data to allow the discovery of new,effective biomarkers.

  7. Monitoring Progression of Amyotrophic Lateral Sclerosis Using Ultrasound Morpho-Textural Muscle Biomarkers: A Pilot Study.

    Science.gov (United States)

    Martínez-Payá, Jacinto J; Ríos-Díaz, José; Medina-Mirapeix, Francesc; Vázquez-Costa, Juan F; Del Baño-Aledo, María Elena

    2018-01-01

    The need is increasing for progression biomarkers that allow the loss of motor neurons in amyotrophic lateral sclerosis (ALS) to be monitored in clinical trials. In this prospective longitudinal study, muscle thickness, echointensity, echovariation and gray level co-occurrence matrix textural features are examined as possible progression ultrasound biomarkers in ALS patients during a 5-mo follow-up period. We subjected 13 patients to 3 measurements for 20 wk. They showed a significant loss of muscle, an evident tendency to loss of thickness and increased echointensity and echovariation. In regard to textural parameters, muscle heterogeneity tended to increase as a result of the neoformation of non-contractile tissue through denervation. Considering some limitations of the study, the quantitative muscle ultrasound biomarkers evaluated showed a promising ability to monitor patients affected by ALS. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  8. Research strategies and the use of nutrient biomarkers in studies of diet and chronic disease.

    Science.gov (United States)

    Prentice, Ross L; Sugar, Elizabeth; Wang, C Y; Neuhouser, Marian; Patterson, Ruth

    2002-12-01

    To provide an account of the state of diet and chronic disease research designs and methods; to discuss the role and potential of aggregate and analytical observational studies and randomised controlled intervention trials; and to propose strategies for strengthening each type of study, with particular emphasis on the use of nutrient biomarkers in cohort study settings. Observations from diet and disease studies conducted over the past 25 years are used to identify the strengths and weaknesses of various study designs that have been used to associate nutrient consumption with chronic disease risk. It is argued that a varied research programme, employing multiple study designs, is needed in response to the widely different biases and constraints that attend aggregate and analytical epidemiological studies and controlled intervention trials. Study design modifications are considered that may be able to enhance the reliability of aggregate and analytical nutritional epidemiological studies. Specifically, the potential of nutrient biomarker measurements that provide an objective assessment of nutrient consumption to enhance analytical study reliability is emphasised. A statistical model for combining nutrient biomarker data with self-report nutrient consumption estimates is described, and related ongoing work on odds ratio parameter estimation is outlined briefly. Finally, a recently completed nutritional biomarker study among 102 postmenopausal women in Seattle is mentioned. The statistical model will be applied to biomarker data on energy expenditure, urinary nitrogen, selected blood fatty acid measurements and various blood micronutrient concentrations, and food frequency self-report data, to identify study subject characteristics, such as body mass, age or socio-economic status, that may be associated with the measurement properties of food frequency nutrient consumption estimates. This information will be crucial for the design of a potential larger nutrient

  9. Consensus Guidelines for CSF and Blood Biobanking for CNS Biomarker Studies

    Directory of Open Access Journals (Sweden)

    Charlotte E. Teunissen

    2011-01-01

    Full Text Available There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in cerebrospinal fluid (CSF are being used in clinical practice. Anti-aquaporin-4 antibodies in serum are currently useful for the diagnosis of neuromyelitis optica (NMO, but we could expect novel CSF biomarkers that help define prognosis and response to treatment for this disease. One of the most critical factors in biomarker research is the inadequate powering of studies performed by single centers. Collaboration between investigators is needed to establish large biobanks of well-defined samples. A key issue in collaboration is to establish standardized protocols for biobanking to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by pre-analytical factors. Here, consensus guidelines for CSF collection and biobanking are presented, based on the guidelines that have been published by the BioMS-eu network for CSF biomarker research. We focussed on CSF collection procedures, pre-analytical factors and high quality clinical and paraclinical information. Importantly, the biobanking protocols are applicable for CSF biobanks for research targeting any neurological disease.

  10. Prediction of the development of reading comprehension: a longitudinal study

    NARCIS (Netherlands)

    Verhoeven, L.T.W.; Leeuwe, J.F.J. van

    2008-01-01

    Specific effects of word decoding, vocabulary and listening comprehension abilities on the development of reading comprehension were longitudinally examined for a representative sample of 2143 Dutch children throughout the elementary school period. An attempt was made to test two theoretical

  11. Biomarkers in Czech workers exposed to 1,3-butadiene: a transitional epidemiologic study

    NARCIS (Netherlands)

    Albertini, Richard J.; Srám, Radim J.; Vacek, Pamela M.; Lynch, Jeremiah; Nicklas, Janice A.; van Sittert, Nico J.; Boogaard, Peter J.; Henderson, Rogene F.; Swenberg, James A.; Tates, Ad D.; Ward, Jonathan B.; Wright, Michael; Ammenheuser, Marinel M.; Binkova, Blanka; Blackwell, Walter; de Zwart, Franz A.; Krako, Dean; Krone, Jennifer; Megens, Hendricus; Musilová, Petra; Rajská, Gabriela; Ranasinghe, Asoka; Rosenblatt, Judah I.; Rössner, Pavel; Rubes, Jiri; Sullivan, Linda; Upton, Patricia; Zwinderman, Ailko H.

    2003-01-01

    A multiinstitutional, transitional epidemiologic study was conducted with a worker population in the Czech Republic to evaluate the utility of a continuum of non-disease biological responses as biomarkers of exposure to 1,3-butadiene (BD)* in an industrial setting. The study site included two BD

  12. Multicollinearity may lead to artificial interaction: an example from a cross sectional study of biomarkers.

    Science.gov (United States)

    Sithisarankul, P; Weaver, V M; Diener-West, M; Strickland, P T

    1997-06-01

    Collinearity is the situation which arises in multiple regression when some or all of the explanatory variables are so highly correlated with one another that it becomes very difficult, if not impossible, to disentangle their influences and obtain a reasonably precise estimate of their effects. Suppressor variable is one of the extreme situations of collinearity that one variable can substantially increase the multiple correlation when combined with a variable that is only modestly correlated with the response variable. In this study, we describe the process by which we disentangled and discovered multicollinearity and its consequences, namely artificial interaction, using the data from cross-sectional quantification of several biomarkers. We showed how the collinearity between one biomarker (blood lead level) and another (urinary trans, trans-muconic acid) and their interaction (blood lead level* urinary trans, trans-muconic acid) can lead to the observed artificial interaction on the third biomarker (urinary 5-aminolevulinic acid).

  13. Evidence that iron accelerates Alzheimer's pathology: a CSF biomarker study.

    Science.gov (United States)

    Ayton, Scott; Diouf, Ibrahima; Bush, Ashley Ian

    2018-05-01

    To investigate whether cerebrospinal fluid (CSF) ferritin (reporting brain iron) is associated with longitudinal changes in CSF β-amyloid (Aβ) and tau. Mixed-effects models of CSF Aβ 1-42 and tau were constructed using data from 296 participants who had baseline measurement of CSF ferritin and annual measurement of CSF tau and Aβ 1-42 for up to 5 years. In subjects with biomarker-confirmed Alzheimer's pathology, high CSF ferritin (>6.2 ng/mL) was associated with accelerated depreciation of CSF Aβ 1-42 (reporting increased plaque formation; p=0.0001). CSF ferritin was neither associated with changes in CSF tau in the same subjects, nor longitudinal changes in CSF tau or Aβ 1-42 in subjects with low baseline pathology. In simulation modelling of the natural history of Aβ deposition, which we estimated to occur over 31.4 years, we predicted that it would take 12.6 years to reach the pathology threshold value of CSF Aβ from healthy normal levels, and this interval is not affected by CSF ferritin. CSF ferritin influences the fall in CSF Aβ over the next phase, where high CSF ferritin accelerated the transition from threshold preclinical Aβ levels to the average level of Alzheimer's subjects from 18.8 to 10.8 years. Iron might facilitate Aβ deposition in Alzheimer's and accelerate the disease process. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. A Japanese cross-sectional multicentre study of biomarkers associated with cardiovascular disease in smokers and non-smokers

    OpenAIRE

    L?dicke, Frank; Magnette, John; Baker, Gizelle; Weitkunat, Rolf

    2015-01-01

    Abstract We performed a cross-sectional, multicentre study in Japan to detect the differences in biomarkers of exposure and cardiovascular biomarkers between smokers and non-smokers. Several clinically relevant cardiovascular biomarkers differed significantly between smokers and non-smokers, including lipid metabolism (high-density lipoprotein cholesterol concentrations ? lower in smokers), inflammation (fibrinogen and white blood cell count ? both higher in smokers), oxidative stress (8-epi-...

  15. Application of a repeat-measure biomarker measurement error model to 2 validation studies: examination of the effect of within-person variation in biomarker measurements.

    Science.gov (United States)

    Preis, Sarah Rosner; Spiegelman, Donna; Zhao, Barbara Bojuan; Moshfegh, Alanna; Baer, David J; Willett, Walter C

    2011-03-15

    Repeat-biomarker measurement error models accounting for systematic correlated within-person error can be used to estimate the correlation coefficient (ρ) and deattenuation factor (λ), used in measurement error correction. These models account for correlated errors in the food frequency questionnaire (FFQ) and the 24-hour diet recall and random within-person variation in the biomarkers. Failure to account for within-person variation in biomarkers can exaggerate correlated errors between FFQs and 24-hour diet recalls. For 2 validation studies, ρ and λ were calculated for total energy and protein density. In the Automated Multiple-Pass Method Validation Study (n=471), doubly labeled water (DLW) and urinary nitrogen (UN) were measured twice in 52 adults approximately 16 months apart (2002-2003), yielding intraclass correlation coefficients of 0.43 for energy (DLW) and 0.54 for protein density (UN/DLW). The deattenuated correlation coefficient for protein density was 0.51 for correlation between the FFQ and the 24-hour diet recall and 0.49 for correlation between the FFQ and the biomarker. Use of repeat-biomarker measurement error models resulted in a ρ of 0.42. These models were similarly applied to the Observing Protein and Energy Nutrition Study (1999-2000). In conclusion, within-person variation in biomarkers can be substantial, and to adequately assess the impact of correlated subject-specific error, this variation should be assessed in validation studies of FFQs. © The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.

  16. A new approach towards biomarker selection in estimation of human exposure to chiral chemicals: a case study of mephedrone.

    Science.gov (United States)

    Castrignanò, Erika; Mardal, Marie; Rydevik, Axel; Miserez, Bram; Ramsey, John; Shine, Trevor; Pantoș, G Dan; Meyer, Markus R; Kasprzyk-Hordern, Barbara

    2017-11-02

    Wastewater-based epidemiology is an innovative approach to estimate public health status using biomarker analysis in wastewater. A new compound detected in wastewater can be a potential biomarker of an emerging trend in public health. However, it is currently difficult to select new biomarkers mainly due to limited human metabolism data. This manuscript presents a new framework, which enables the identification and selection of new biomarkers of human exposure to drugs with scarce or unknown human metabolism data. Mephedrone was targeted to elucidate the assessment of biomarkers for emerging drugs of abuse using a four-step analytical procedure. This framework consists of: (i) identification of possible metabolic biomarkers present in wastewater using an in-vivo study; (ii) verification of chiral signature of the target compound; (iii) confirmation of human metabolic residues in in-vivo/vitro studies and (iv) verification of stability of biomarkers in wastewater. Mephedrone was selected as a suitable biomarker due to its high stability profile in wastewater. Its enantiomeric profiling was studied for the first time in biological and environmental matrices, showing stereoselective metabolism of mephedrone in humans. Further biomarker candidates were also proposed for future investigation: 4'-carboxy-mephedrone, 4'-carboxy-normephedrone, 1-dihydro-mephedrone, 1-dihydro-normephedrone and 4'-hydroxy-normephedrone.

  17. Comprehensive proteomic analysis of human pancreatic juice

    DEFF Research Database (Denmark)

    Grønborg, Mads; Bunkenborg, Jakob; Kristiansen, Troels Zakarias

    2004-01-01

    Proteomic technologies provide an excellent means for analysis of body fluids for cataloging protein constituents and identifying biomarkers for early detection of cancers. The biomarkers currently available for pancreatic cancer, such as CA19-9, lack adequate sensitivity and specificity...... contributing to late diagnosis of this deadly disease. In this study, we carried out a comprehensive characterization of the "pancreatic juice proteome" in patients with pancreatic adenocarcinoma. Pancreatic juice was first fractionated by 1-dimensional gel electrophoresis and subsequently analyzed by liquid...... in this study could be directly assessed for their potential as biomarkers for pancreatic cancer by quantitative proteomics methods or immunoassays....

  18. Metabolite Profiling in the Pursuit of Biomarkers for IVF Outcome: The Case for Metabolomics Studies

    Directory of Open Access Journals (Sweden)

    C. McRae

    2013-01-01

    Full Text Available Background. This paper presents the literature on biomarkers of in vitro fertilisation (IVF outcome, demonstrating the progression of these studies towards metabolite profiling, specifically metabolomics. The need for more, and improved, metabolomics studies in the field of assisted conception is discussed. Methods. Searches were performed on ISI Web of Knowledge SM for literature associated with biomarkers of oocyte and embryo quality, and biomarkers of IVF outcome in embryo culture medium, follicular fluid (FF, and blood plasma in female mammals. Results. Metabolomics in the field of female reproduction is still in its infancy. Metabolomics investigations of embryo culture medium for embryo selection have been the most common, but only within the last five years. Only in 2012 has the first metabolomics investigation of FF for biomarkers of oocyte quality been reported. The only metabolomics studies of human blood plasma in this context have been aimed at identifying women with polycystic ovary syndrome (PCOS. Conclusions. Metabolomics is becoming more established in the field of assisted conception, but the studies performed so far have been preliminary and not all potential applications have yet been explored. With further improved metabolomics studies, the possibility of identifying a method for predicting IVF outcome may become a reality.

  19. Effect of vitamin levels on biomarkers of exposure and oxidative damage – The EXPAH study

    Czech Academy of Sciences Publication Activity Database

    Šrám, Radim; Farmer, P.; Singh, R.; Garte, S.; Kalina, I.; Popov, T. A.; Binková, Blanka; Ragin, C.; Taioli, E.

    2009-01-01

    Roč. 672, č. 2 (2009), s. 129-134 ISSN 1383-5718 Institutional research plan: CEZ:AV0Z50390512 Keywords : molecular epidemiology * cross-sectional study * biomarkers of exposure Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.552, year: 2009

  20. Metabolism and Biomarkers of Heterocyclic Aromatic Amines in Molecular Epidemiology Studies: Lessons Learned from Aromatic Amines

    Science.gov (United States)

    2011-01-01

    Aromatic amines and heterocyclic aromatic amines (HAAs) are structurally related classes of carcinogens that are formed during the combustion of tobacco or during the high-temperature cooking of meats. Both classes of procarcinogens undergo metabolic activation by N-hydroxylation of the exocyclic amine group, to produce a common proposed intermediate, the arylnitrenium ion, which is the critical metabolite implicated in toxicity and DNA damage. However, the biochemistry and chemical properties of these compounds are distinct and different biomarkers of aromatic amines and HAAs have been developed for human biomonitoring studies. Hemoglobin adducts have been extensively used as biomarkers to monitor occupational and environmental exposures to a number of aromatic amines; however, HAAs do not form hemoglobin adducts at appreciable levels and other biomarkers have been sought. A number of epidemiologic studies that have investigated dietary consumption of well-done meat in relation to various tumor sites reported a positive association between cancer risk and well-done meat consumption, although some studies have shown no associations between well-done meat and cancer risk. A major limiting factor in most epidemiological studies is the uncertainty in quantitative estimates of chronic exposure to HAAs and, thus, the association of HAAs formed in cooked meat and cancer risk has been difficult to establish. There is a critical need to establish long-term biomarkers of HAAs that can be implemented in molecular epidemioIogy studies. In this review article, we highlight and contrast the biochemistry of several prototypical carcinogenic aromatic amines and HAAs to which humans are chronically exposed. The biochemical properties and the impact of polymorphisms of the major xenobiotic-metabolizing enzymes on the biological effects of these chemicals are examined. Lastly, the analytical approaches that have been successfully employed to biomonitor aromatic amines and HAAs, and

  1. Chasing the effects of Pre-analytical Confounders - a Multicentre Study on CSF-AD biomarkers

    Directory of Open Access Journals (Sweden)

    Maria Joao Leitao

    2015-07-01

    Full Text Available Core cerebrospinal fluid (CSF biomarkers-Aβ42, Tau and pTau–have been recently incorporated in the revised criteria for Alzheimer’s disease (AD. However, their widespread clinical application lacks standardization. Pre-analytical sample handling and storage play an important role in the reliable measurement of these biomarkers across laboratories. In this study, we aim to surpass the efforts from previous studies, by employing a multicentre approach to assess the impact of less studied CSF pre-analytical confounders in AD-biomarkers quantification. Four different centres participated in this study and followed the same established protocol. CSF samples were analysed for three biomarkers (Aβ42, Tau and pTau and tested for different spinning conditions (temperature: Room temperature (RT vs. 4oC; speed: 500g vs. 2000g vs. 3000g, storage volume variations (25%, 50% and 75% of tube total volume as well as freezing-thaw cycles (up to 5 cyles. The influence of sample routine parameters, inter-centre variability and relative value of each biomarker (reported as normal/abnormal, was analysed. Centrifugation conditions did not influence biomarkers levels, except for samples with a high CSF total protein content, where either non centrifugation or centrifugation at RT, compared to 4ºC, led to higher Aβ42 levels. Reducing CSF storage volume from 75% to 50% of total tube capacity, decreased Aβ42 concentration (within analytical CV of the assay, whereas no change in Tau or pTau was observed. Moreover, the concentration of Tau and pTau appears to be stable up to 5 freeze-thaw cycles, whereas Aβ42 levels decrease if CSF is freeze-thawed more than 3 times. This systematic study reinforces the need for CSF centrifugation at 4ºC prior to storage and highlights the influence of storage conditions in Aβ42 levels. This study contributes to the establishment of harmonized standard operating procedures that will help reducing inter-lab variability of CSF

  2. Blood-borne biomarkers of mortality risk: systematic review of cohort studies.

    Directory of Open Access Journals (Sweden)

    Evelyn Barron

    Full Text Available Lifespan and the proportion of older people in the population are increasing, with far reaching consequences for the social, political and economic landscape. Unless accompanied by an increase in health span, increases in age-related diseases will increase the burden on health care resources. Intervention studies to enhance healthy ageing need appropriate outcome measures, such as blood-borne biomarkers, which are easily obtainable, cost-effective, and widely accepted. To date there have been no systematic reviews of blood-borne biomarkers of mortality.To conduct a systematic review to identify available blood-borne biomarkers of mortality that can be used to predict healthy ageing post-retirement.Four databases (Medline, Embase, Scopus, Web of Science were searched. We included prospective cohort studies with a minimum of two years follow up and data available for participants with a mean age of 50 to 75 years at baseline.From a total of 11,555 studies identified in initial searches, 23 fulfilled the inclusion criteria. Fifty-one blood borne biomarkers potentially predictive of mortality risk were identified. In total, 20 biomarkers were associated with mortality risk. Meta-analyses of mortality risk showed significant associations with C-reactive protein (Hazard ratios for all-cause mortality 1.42, p<0.001; Cancer-mortality 1.62, p<0.009; CVD-mortality 1.31, p = 0.033, N Terminal-pro brain natriuretic peptide (Hazard ratios for all-cause mortality 1.43, p<0.001; CHD-mortality 1.58, p<0.001; CVD-mortality 1.67, p<0.001 and white blood cell count (Hazard ratios for all-cause mortality 1.36, p = 0.001. There was also evidence that brain natriuretic peptide, cholesterol fractions, erythrocyte sedimentation rate, fibrinogen, granulocytes, homocysteine, intercellular adhesion molecule-1, neutrophils, osteoprotegerin, procollagen type III aminoterminal peptide, serum uric acid, soluble urokinase plasminogen activator receptor, tissue inhibitor of

  3. Plasma soluble prion protein, a potential biomarker for sport-related concussions: a pilot study.

    Science.gov (United States)

    Pham, Nam; Akonasu, Hungbo; Shishkin, Rhonda; Taghibiglou, Changiz

    2015-01-01

    Sport-related mild traumatic brain injury (mTBI) or concussion is a significant health concern to athletes with potential long-term consequences. The diagnosis of sport concussion and return to sport decision making is one of the greatest challenges facing health care clinicians working in sports. Blood biomarkers have recently demonstrated their potential in assisting the detection of brain injury particularly, in those cases with no obvious physical injury. We have recently discovered plasma soluble cellular prion protein (PrP(C)) as a potential reliable biomarker for blast induced TBI (bTBI) in a rodent animal model. In order to explore the application of this novel TBI biomarker to sport-related concussion, we conducted a pilot study at the University of Saskatchewan (U of S) by recruiting athlete and non-athlete 18 to 30 year-old students. Using a modified quantitative ELISA method, we first established normal values for the plasma soluble PrP(C) in male and female students. The measured plasma soluble PrP(C) in confirmed concussion cases demonstrated a significant elevation of this analyte in post-concussion samples. Data collected from our pilot study indicates that the plasma soluble PrP(C) is a potential biomarker for sport-related concussion, which may be further developed into a clinical diagnostic tool to assist clinicians in the assessment of sport concussion and return-to-play decision making.

  4. Inflammatory biomarkers and academic performance in youth. The UP & DOWN Study.

    Science.gov (United States)

    Esteban-Cornejo, Irene; Martinez-Gomez, David; Gómez-Martínez, Sonia; Del Campo-Vecino, Juan; Fernández-Santos, Jorge; Castro-Piñero, Jose; Marcos, Ascensión; Veiga, Oscar L

    2016-05-01

    Inflammation influences cognitive development in infants and older adults, however, how inflammation may affect academic development during childhood and adolescence remains to be elucidated. This study aimed to examine the association between inflammatory biomarkers and academic performance in children and adolescents. A total of 494 youth (238 girls) aged 10.6 ± 3.4 years participated in the study. Four inflammatory biomarkers were selected: C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and white blood cell (WBC) count. An inflammatory index was created using the above mentioned biomarkers. Academic performance was assessed through schools records. Results showed that three of the four inflammatory biomarkers (CRP, IL-6 and WBC) and the inflammatory index were negatively associated with all academic indicators (β values ranging from -0.094 to -0.217, all Pacademic indicators compared with youth in the middle tertile (scores ranging from -0.578 to -0.344) and in the lowest tertile (scores ranging from -0.678 to -0.381). In conclusion, inflammation may impair academic performance independently of body fat levels in youth. Our results are of importance because the consequences of childhood and adolescence inflammation tend to continue into adulthood. Lifestyle interventions in youth may be promising in reducing levels of inflammation beyond the reduction in body fat in order to achieve cognitive benefits. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Plasma soluble prion protein, a potential biomarker for sport-related concussions: a pilot study.

    Directory of Open Access Journals (Sweden)

    Nam Pham

    Full Text Available Sport-related mild traumatic brain injury (mTBI or concussion is a significant health concern to athletes with potential long-term consequences. The diagnosis of sport concussion and return to sport decision making is one of the greatest challenges facing health care clinicians working in sports. Blood biomarkers have recently demonstrated their potential in assisting the detection of brain injury particularly, in those cases with no obvious physical injury. We have recently discovered plasma soluble cellular prion protein (PrP(C as a potential reliable biomarker for blast induced TBI (bTBI in a rodent animal model. In order to explore the application of this novel TBI biomarker to sport-related concussion, we conducted a pilot study at the University of Saskatchewan (U of S by recruiting athlete and non-athlete 18 to 30 year-old students. Using a modified quantitative ELISA method, we first established normal values for the plasma soluble PrP(C in male and female students. The measured plasma soluble PrP(C in confirmed concussion cases demonstrated a significant elevation of this analyte in post-concussion samples. Data collected from our pilot study indicates that the plasma soluble PrP(C is a potential biomarker for sport-related concussion, which may be further developed into a clinical diagnostic tool to assist clinicians in the assessment of sport concussion and return-to-play decision making.

  6. A view of studies on listening comprehension within the theory of working memory

    OpenAIRE

    福田, 倫子

    2004-01-01

    The present paper discusses four aspects : (1) the relation between the process of language comprehension and working memory, (2) overview of studies on working memory model, (3) application of the working memory to studies of listening comprehension in previous studies, (4) potentiality of application of the working memory model to studies of listening comprehension of second language acquisition.

  7. Comprehensive studies on irradiated single-crystal diamond sensors

    Energy Technology Data Exchange (ETDEWEB)

    Stegler, Martin [DESY, Zeuthen (Germany)

    2015-07-01

    Single-crystal diamond sensors are used as part of the Beam and Radiation Instrumentation and Luminosity (BRIL) projects of the CMS experiment. Due to an upgrade of the Fast Beam Conditions Monitor (BCM1F) these diamond sensors are exchanged and the irradiated ones are now used for comprehensive studies. Current over voltage (IV), current over time (CT) and charge collection efficiency (CCE) measurements were performed for a better understanding of the radiation damage incurred during operation and to compensate in the future. The effect of illumination with various light sources on the charge collection efficiency was investigated and led to interesting results. Intensity and wavelength of the light were varied for deeper insight of polarization effects.

  8. Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials.

    Science.gov (United States)

    Suh, James H; Johnson, Adrienne; Albacker, Lee; Wang, Kai; Chmielecki, Juliann; Frampton, Garrett; Gay, Laurie; Elvin, Julia A; Vergilio, Jo-Anne; Ali, Siraj; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S

    2016-06-01

    The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) test, in clinical practice. CGP was performed to a mean coverage depth of 576× on 6,832 consecutive cases of NSCLC (2012-2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes. The median age of the patients was 64 years (range: 13-88 years) and 53% were female. Among the patients studied, 4,876 (71%) harbored at least one GA involving EGFR (20%), ALK (4.1%), BRAF (5.7%), ERBB2 (6.0%), MET (5.6%), ROS1 (1.5%), RET (2.4%), or KRAS (32%). In the remaining cohort of lung AD without these known drivers, 273 cancer-related genes were altered in at least 0.1% of cases, including STK11 (21%), NF1 (13%), MYC (9.8%), RICTOR (6.4%), PIK3CA (5.4%), CDK4 (4.3%), CCND1 (4.0%), BRCA2 (2.5%), NRAS (2.3%), BRCA1 (1.7%), MAP2K1 (1.2%), HRAS (0.7%), NTRK1 (0.7%), and NTRK3 (0.2%). CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS. Furthermore, without additional tissue use or cost, CGP identifies patients with "pan-negative" lung AD who may benefit from enrollment in mechanism-driven clinical trials. National Comprehensive Cancer Network guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma

  9. Urinary collagen IV and πGST: potential biomarkers for detecting localized kidney injury in diabetes--a pilot study.

    LENUS (Irish Health Repository)

    Cawood, T J

    2010-01-01

    Urinary biomarkers can identify damage to specific parts of the nephron. We performed a cross-sectional study to characterise the pattern of diabetic nephropathy using urinary biomarkers of glomerular fibrosis (collagen IV), proximal tubular damage (α-glutathione-S-transferase, GST) and distal tubular damage (πGST).

  10. Circulating Long Noncoding RNAs as Potential Biomarkers of Sepsis: A Preliminary Study.

    Science.gov (United States)

    Dai, Yu; Liang, Zhixin; Li, Yulin; Li, Chunsun; Chen, Liangan

    2017-11-01

    Long noncoding RNAs (lncRNAs) are becoming promising biomarker candidates in various diseases as assessed via sequencing technologies. Sepsis is a life-threatening disease without ideal biomarkers. The aim of this study was to investigate the expression profile of lncRNAs in the peripheral blood of sepsis patients and to find potential biomarkers of sepsis. A lncRNA expression profile was performed using peripheral blood from three sepsis patients and three healthy volunteers using microarray screening. The differentially expressed lncRNAs were validated by real-time quantitative polymerase chain reaction (qRT-PCR) in a further set of 22 sepsis patients and 22 healthy volunteers. Among 1316 differentially expressed lncRNAs, 771 were downregulated and 545 were upregulated. Results of the qRT-PCR were consistent with the microarray data. lncRNA ENST00000452391.1, uc001vji.1, and uc021zxw.1 were significantly differentially expressed between sepsis patients and healthy volunteers. Moreover, lncRNA ENST00000504301.1 and ENST00000452391.1 were significantly differentially expressed between sepsis survivors and nonsurvivors. The lncRNA expression profile in the peripheral blood of sepsis patients significantly differed from that of healthy volunteers. Circulating lncRNAs may be good candidates for sepsis biomarkers.

  11. A simulation study on estimating biomarker-treatment interaction effects in randomized trials with prognostic variables.

    Science.gov (United States)

    Haller, Bernhard; Ulm, Kurt

    2018-02-20

    To individualize treatment decisions based on patient characteristics, identification of an interaction between a biomarker and treatment is necessary. Often such potential interactions are analysed using data from randomized clinical trials intended for comparison of two treatments. Tests of interactions are often lacking statistical power and we investigated if and how a consideration of further prognostic variables can improve power and decrease the bias of estimated biomarker-treatment interactions in randomized clinical trials with time-to-event outcomes. A simulation study was performed to assess how prognostic factors affect the estimate of the biomarker-treatment interaction for a time-to-event outcome, when different approaches, like ignoring other prognostic factors, including all available covariates or using variable selection strategies, are applied. Different scenarios regarding the proportion of censored observations, the correlation structure between the covariate of interest and further potential prognostic variables, and the strength of the interaction were considered. The simulation study revealed that in a regression model for estimating a biomarker-treatment interaction, the probability of detecting a biomarker-treatment interaction can be increased by including prognostic variables that are associated with the outcome, and that the interaction estimate is biased when relevant prognostic variables are not considered. However, the probability of a false-positive finding increases if too many potential predictors are included or if variable selection is performed inadequately. We recommend undertaking an adequate literature search before data analysis to derive information about potential prognostic variables and to gain power for detecting true interaction effects and pre-specifying analyses to avoid selective reporting and increased false-positive rates.

  12. Reading Comprehension and Tolerance against Comprehension Ambiguities: An Empirical Study of Iranian GFL-Learners in Communicative Education

    Science.gov (United States)

    Haghani, Nader; Bahmannejad, Fereshteh

    2018-01-01

    The present study examines the influence of ambiguity tolerance on the performance of Iranian GFL-learners (Note 1) at level B1 in the processing of gap-filling-text tests. It is assumed that learners with more tolerance of ambiguity achieve better results in the reading comprehension or in the contextual guessing of the omitted words. 34 GFL…

  13. Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.

    Science.gov (United States)

    Yee, S W; Giacomini, M M; Hsueh, C-H; Weitz, D; Liang, X; Goswami, S; Kinchen, J M; Coelho, A; Zur, A A; Mertsch, K; Brian, W; Kroetz, D L; Giacomini, K M

    2016-11-01

    Transporter-mediated drug-drug interactions (DDIs) are a major cause of drug toxicities. Using published genome-wide association studies (GWAS) of the human metabolome, we identified 20 metabolites associated with genetic variants in organic anion transporter, OATP1B1 (P acids and fatty acid dicarboxylates were among the metabolites discovered using both GWAS and CSA administration. In vitro studies confirmed tetradecanedioate (TDA) and hexadecanedioate (HDA) were novel substrates of OATP1B1 as well as OAT1 and OAT3. This study highlights the use of multiple datasets for the discovery of endogenous metabolites that represent potential in vivo biomarkers for transporter-mediated DDIs. Future studies are needed to determine whether these metabolites can serve as qualified biomarkers for organic anion transporters. Quantitative relationships between metabolite levels and modulation of transporters should be established. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  14. A comprehensive combustion chemistry study of 2,5-dimethylhexane

    KAUST Repository

    Sarathy, Mani

    2014-06-01

    Iso-paraffinic molecular structures larger than seven carbon atoms in chain length are commonly found in conventional petroleum, Fischer-Tropsch (FT), and other alternative hydrocarbon fuels, but little research has been done on their combustion behavior. Recent studies have focused on either mono-methylated alkanes and/or highly branched compounds (e.g., 2,2,4-trimethylpentane). In order to better understand the combustion characteristics of real fuels, this study presents new experimental data for the oxidation of 2,5-dimethylhexane under a wide variety of temperature, pressure, and equivalence ratio conditions. This new dataset includes jet stirred reactor speciation, shock tube ignition delay, and rapid compression machine ignition delay, which builds upon recently published data for counterflow flame ignition, extinction, and speciation profiles. The low and high temperature oxidation of 2,5-dimethylhexane has been simulated with a comprehensive chemical kinetic model developed using established reaction rate rules. The agreement between the model and data is presented, along with suggestions for improving model predictions. The oxidation behavior of 2,5-dimethylhexane is compared with oxidation of other octane isomers to confirm the effects of branching on low and intermediate temperature fuel reactivity. The model is used to elucidate the structural features and reaction pathways responsible for inhibiting the reactivity of 2,5-dimethylhexane. © 2014 The Combustion Institute.

  15. A comprehensive combustion chemistry study of 2,5-dimethylhexane

    KAUST Repository

    Sarathy, Mani; Javed, Tamour; Karsenty, Florent; Heufer, Alexander; Wang, Weijing; Park, Sungwoo; Elwardani, Ahmed Elsaid; Farooq, Aamir; Westbrook, Charles K.; Pitz, William J.; Oehlschlaeger, Matthew A.; Dayma, Guillaume; Curran, Henry J.; Dagaut, P.

    2014-01-01

    Iso-paraffinic molecular structures larger than seven carbon atoms in chain length are commonly found in conventional petroleum, Fischer-Tropsch (FT), and other alternative hydrocarbon fuels, but little research has been done on their combustion behavior. Recent studies have focused on either mono-methylated alkanes and/or highly branched compounds (e.g., 2,2,4-trimethylpentane). In order to better understand the combustion characteristics of real fuels, this study presents new experimental data for the oxidation of 2,5-dimethylhexane under a wide variety of temperature, pressure, and equivalence ratio conditions. This new dataset includes jet stirred reactor speciation, shock tube ignition delay, and rapid compression machine ignition delay, which builds upon recently published data for counterflow flame ignition, extinction, and speciation profiles. The low and high temperature oxidation of 2,5-dimethylhexane has been simulated with a comprehensive chemical kinetic model developed using established reaction rate rules. The agreement between the model and data is presented, along with suggestions for improving model predictions. The oxidation behavior of 2,5-dimethylhexane is compared with oxidation of other octane isomers to confirm the effects of branching on low and intermediate temperature fuel reactivity. The model is used to elucidate the structural features and reaction pathways responsible for inhibiting the reactivity of 2,5-dimethylhexane. © 2014 The Combustion Institute.

  16. Thermal stability of thiophene biomarkers as studied by hydrous pyrolysis

    NARCIS (Netherlands)

    Sinninghe Damsté, J.S.; Koopmans, M.P.; Lewan, M.D.; Leeuw, J.W. de

    1995-01-01

    An immature (Ro = 0.25%) sulphur-rich calcareous shale from the Gessoso-solfifera Formation (Messinian) in the Vena del Gesso Basin (northern Italy) was artificially matured by hydrous pyrolysis at constant temperatures ranging from 160 to 330°C for 72 h to study the applicability of alkylthiophenes

  17. Sedentary leisure time behavior, snacking habits and cardiovascular biomarkers: the Inter99 Study

    DEFF Research Database (Denmark)

    Frydenlund, Gitte; Jørgensen, Torben; Toft, Ulla

    2011-01-01

    Aim: To explore the association between sedentary leisure time behavior (SLTB) and cardiovascular biomarkers, taking into account snacking habits, alcohol intake and physical activity level. Design: Cross-sectional. Methods: Study participants were recruited from the 5-year follow-up of a populat......Aim: To explore the association between sedentary leisure time behavior (SLTB) and cardiovascular biomarkers, taking into account snacking habits, alcohol intake and physical activity level. Design: Cross-sectional. Methods: Study participants were recruited from the 5-year follow...... non-significant in men (ß = 0.9924, [0.9839; 1.0011]) and women (ß = 0.9932, [0.8605; 1.0014]). Conclusion: SLTB appears to be an independent CVD risk factor, regardless of snacking habits and physical activity....

  18. Deep Panuke offshore gas development comprehensive study report : Executive summary

    International Nuclear Information System (INIS)

    2002-10-01

    A project was proposed by EnCana Corporation (EnCana) for the development of the Deep Panuke Offshore Gas Development Project. Located offshore the Scotian Shelf, approximately 175 kilometres southeast of Goldboro, Nova Scotia and 250 kilometres southeast of Halifax, the development of this natural gas reservoir would allow EnCana to derive economic benefit from licences issued under the Canada-Nova Scotia Offshore Petroleum Resources Accord Implementation Act and the Canada-Nova Scotia Offshore Petroleum Resources Accord Implementation (Nova Scotia) Act. The Canadian Environmental Assessment Act required that a comprehensive study report be prepared, and the results were presented in this document. Consisting of three bottom-founded platforms in a water depth of approximately 40 metres, the wellhead platform would be used for dry wellheads, wellhead control system, and production manifolds. All power generation and processing equipment would be located on the production platform, and the accommodations platform would consist of the utilities, helicopter landing pad, refueling station and crew accommodations. It was determined that the Deep Panuke project was unlikely to result in adverse environmental effects. The offshore oil and gas industry in Atlantic Canada would benefit from this development as a result of the establishment of a viable facility and operation

  19. Building a comprehensive geriatric health care system: a case study.

    Science.gov (United States)

    Bleiweiss, L; Simson, S

    1976-01-01

    This case study focuses on the efforts of three urban medical care institutions--a Health Maintenance Organization, a nursing home, and a university hospital--to form an interorganizational relationship. The purpose of the relationship was to utilize the services of the three organizations in order to respond to the comprehensive health needs of an urban geriatric population. Movements in this triadic organizational relationship are described and analyzed in terms of four conceptual stages--exploration, negotiation, interaction and performance, and termination. Problems arising during these stages were not resolved and the relationship was terminated after approximately two years of existence. A sociological discussion of the case focuses on why the relationship failed. The organizational relationship was disrupted by three stresses that occurred during the four stages of the relationship. Stresses emerged for each organization in the areas of organizational integration, professional coordination, and environmental adaptation, making it difficult for the three to become integrated into an organizational system. As a result, the HMO, the nursing home, and the hospital did not benefit from relationships that could have enabled them to develop the multi-organizational system necessary to sustain an innovative, comprehansive geriatric health project. If, as Whitehead said, the greatest invention of the nineteenth century was the invention of the method of invention, the task of the succedding century has been to organize inventiveness. The difference is not in the nature of invention or of inventors, but in the manner in which the context of social institutions is organized for their support.

  20. The Reading Comprehension Strategies of Second Language Learners: A Spanish-English Study

    Science.gov (United States)

    Acosta Caballero, Karen Anelice

    2012-01-01

    Reading comprehension of school-aged students is an important topic of research; however, research on the reading comprehension of adult foreign/second language learners whose first language is English is limited, especially studies investigating the reading comprehension strategies that readers of different proficiency levels use when they…

  1. Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study

    Science.gov (United States)

    Liu, Kathleen D.; Siew, Edward D.; Reeves, W. Brian; Himmelfarb, Jonathan; Go, Alan S.; Hsu, Chi-yuan; Bennett, Michael R.; Devarajan, Prasad; Ikizler, T. Alp; Kaufman, James S.; Kimmel, Paul L.; Chinchilli, Vernon M.; Parikh, Chirag R.

    2016-01-01

    Background Although stored urine samples are often used in biomarker studies focused on acute and chronic kidney disease, how storage time impacts biomarker levels is not well understood. Methods 866 subjects enrolled in the NIDDK-sponsored ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study were included. Samples were processed under standard conditions and stored at -70°C until analyzed. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and liver fatty acid binding protein (L-FABP) were measured in urine samples collected during the index hospitalization or an outpatient visit 3 months later. Mixed effects models were used to determine the effect of storage time on biomarker levels and stratified by visit. Results Median storage was 17.8 months (25–75% IQR 10.6–23.7) for samples from the index hospitalization and 14.6 months (IQR 7.3–20.4) for outpatient samples. In the mixed effects models, the only significant association between storage time and biomarker concentration was for KIM-1 in outpatient samples, where each month of storage was associated with a 1.7% decrease (95% CI -3% to -0.3%). There was no relationship between storage time and KIM-1 levels in samples from the index hospitalization. Conclusion There was no significant impact of storage time over a median of 18 months on urine KIM-1, NGAL, IL-18 or L-FABP in hospitalized samples; a statistically significant effect towards a decrease over time was noted for KIM-1 in outpatient samples. Additional studies are needed to determine whether longer periods of storage at -70°C systematically impact levels of these analytes. PMID:27788160

  2. Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study.

    Directory of Open Access Journals (Sweden)

    Kathleen D Liu

    Full Text Available Although stored urine samples are often used in biomarker studies focused on acute and chronic kidney disease, how storage time impacts biomarker levels is not well understood.866 subjects enrolled in the NIDDK-sponsored ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI Study were included. Samples were processed under standard conditions and stored at -70°C until analyzed. Kidney injury molecule-1 (KIM-1, neutrophil gelatinase-associated lipocalin (NGAL, interleukin-18 (IL-18, and liver fatty acid binding protein (L-FABP were measured in urine samples collected during the index hospitalization or an outpatient visit 3 months later. Mixed effects models were used to determine the effect of storage time on biomarker levels and stratified by visit.Median storage was 17.8 months (25-75% IQR 10.6-23.7 for samples from the index hospitalization and 14.6 months (IQR 7.3-20.4 for outpatient samples. In the mixed effects models, the only significant association between storage time and biomarker concentration was for KIM-1 in outpatient samples, where each month of storage was associated with a 1.7% decrease (95% CI -3% to -0.3%. There was no relationship between storage time and KIM-1 levels in samples from the index hospitalization.There was no significant impact of storage time over a median of 18 months on urine KIM-1, NGAL, IL-18 or L-FABP in hospitalized samples; a statistically significant effect towards a decrease over time was noted for KIM-1 in outpatient samples. Additional studies are needed to determine whether longer periods of storage at -70°C systematically impact levels of these analytes.

  3. Imaging studies and biomarkers to detect clinically meaningful vesicoureteral reflux

    Directory of Open Access Journals (Sweden)

    Michaella Maloney Prasad

    2017-06-01

    Full Text Available The work-up of a febrile urinary tract infection is generally performed to detect vesicoureteral reflux (VUR and its possible complications. The imaging modalities most commonly used for this purpose are renal-bladder ultrasound, voiding cystourethrogram and dimercapto-succinic acid scan. These studies each contribute valuable information, but carry individual benefits and limitations that may impact their efficacy. Biochemical markers are not commonly used in pediatric urology to diagnose or differentiate high-risk disease, but this is the emerging frontier, which will hopefully change our approach to VUR in the future. As it becomes more apparent that there is tremendous clinical variation within grades of VUR, the need to distinguish clinically significant from insignificant disease grows. The unfortunate truth about VUR is that recommendations for treatment may be inconsistent. Nuances in clinical decision-making will always exist, but opinions for medical versus surgical intervention should be more standardized, based on risk of injury to the kidney.

  4. An exploratory study of inflammatory cytokines as prognostic biomarkers in patients with ductal pancreatic adenocarcinoma.

    Science.gov (United States)

    Dima, Simona O; Tanase, Cristiana; Albulescu, Radu; Herlea, Vlad; Chivu-Economescu, Mihaela; Purnichescu-Purtan, Raluca; Dumitrascu, Traian; Duda, Dan G; Popescu, Irinel

    2012-10-01

    We measured the serum concentration of a panel of inflammatory cytokines and evaluated their association with circulating proangiogenic biomarkers and with outcome in patients with pancreatic ductal adenocarcinoma (PDAC). We collected serum samples from 36 patients with PDAC, 9 patients with chronic pancreatitis, and 22 healthy volunteers as a control. Inflammatory cytokines and proangiogenic biomarkers were measured using the multianalyte xMAP array and carcinoembryonic antigen (CEA) and carbohydrate 19-9 by immunoassay. Patients with PDAC had higher circulating levels of interleukin 6 (IL-6) than those of patients with pancreatitis or healthy individuals and higher levels of IL-10 and tumor necrosis factor α (TNF-α) compared with those of healthy individuals. In patients with PDAC, circulating IL-6, TNF-α, IL-1β, and IL-10 correlated with serum concentrations of vascular endothelial growth factor and basic fibroblast growth factor; circulating IL-6, IL-1β, and TNF-α correlated with carbohydrate 19-9; and IL-8, IL-10, and TNF-α correlated with CEA levels. Circulating IL-8, TNF-α, and CEA; tumor stage; and lymph node metastases were associated with a poor outcome. The results of this exploratory study indicate that inflammatory cytokines should be pursued as potential prognostic biomarkers as well as targets for therapy in larger studies in PDAC.

  5. Serum biomarkers for the early diagnosis of TIA: The MIND-TIA study protocol.

    Science.gov (United States)

    Dolmans, L Servaas; Rutten, Frans H; El Bartelink, Marie-Louise; Seppenwoolde, Gerdien; van Delft, Sanne; Kappelle, L Jaap; Hoes, Arno W

    2015-07-28

    A Transient Ischaemic Attack (TIA) bears a high risk of a subsequent ischaemic stroke. Adequate diagnosis of a TIA should be followed immediately by the start of appropriate preventive therapy, including antiplatelets. The diagnosis of a TIA based on symptoms and signs only is notoriously difficult and biomarkers of brain ischaemia might improve the recognition, and target management and prognosis of TIA patients. Our aim is to quantify the added diagnostic value of serum biomarkers of brain ischaemia in patients suspected of TIA. a cross-sectional diagnostic accuracy study with an additional six month follow-up period. 350 patients suspected of TIA in the primary care setting. Patients suspected of a TIA will be recruited by at least 200 general practitioners (GPs) in the catchment area of seven TIA outpatient clinics willing to participate in the study. In all patients a blood sample will be drawn as soon as possible after the patient has contacted the GP, but at least within 72 h after onset of symptoms. Participants will be referred by the GP to the regional TIA outpatient clinic for additional investigations, including brain imaging. The 'definite' diagnosis (reference standard) will be made by a panel consisting of three experienced neurologists who will use all available diagnostic information and the clinical information obtained during the outpatient clinic assessment, and a six month follow-up period. The diagnostic accuracy, and value in addition to signs and symptoms of candidate serum biomarkers will be assessed in terms of discrimination with C statistics, and calibration with plots. We aim to include 350 suspected cases, with 250 patients with indeed definite TIA (or minor stroke) according to the panel. We hope to find novel biomarkers that will enable a rapid and accurate diagnosis of TIA. This would largely improve the management and prognosis of such patients. ClinicalTrials.gov Identifier NCT01954329.

  6. Biomarkers for acute kidney injury in decompensated cirrhosis: A Prospective Study.

    Science.gov (United States)

    Jaques, David A; Spahr, Laurent; Berra, Gregory; Poffet, Vincent; Lescuyer, Pierre; Gerstel, Eric; Garin, Nicolas; Martin, Pierre-Yves; Ponte, Belen

    2018-01-25

    Acute kidney injury (AKI) is a frequent complication in cirrhotic patients. As serum creatinine is a poor marker of renal function in this population, we aimed to study the utility of several biomarkers in this context. A prospective study was conducted in hospitalized patients with decompensated cirrhosis. Serum creatinine (SCr), Cystatin C (CystC), NGAL and urinary NGAL, KIM-1, protein, albumin and sodium were measured on three separate occasions. Renal resistive index (RRI) was obtained. We analyzed the value of these biomarkers to determine the presence of AKI, its etiology [prerenal, acute tubular necrosis (ATN), or hepatorenal (HRS)], its severity and a composite clinical outcome at 30 days (death, dialysis and intensive care admission). We included 105 patients, of which 55 had AKI. SCr, CystC, NGAL (plasma and urinary), urinary sodium and RRI at inclusion were independently associated with the presence of AKI. SCr, CystC and plasma NGAL were able to predict the subsequent development of AKI. Pre-renal state showed lower levels of SCr, NGAL (plasma and urinary) and RRI. ATN patients had high levels of NGAL (plasma and urinary) as well as urinary protein and sodium. HRS patients presented an intermediate pattern. All biomarkers paralleled the severity of AKI. SCr, CystC and plasma NGAL predicted the development of the composite clinical outcome with the same performance as the MELD score. In patients with decompensated cirrhosis, early measurement of renal biomarkers provides valuable information on AKI etiology. It could also improve AKI diagnosis and prognosis. This article is protected by copyright. All rights reserved.

  7. Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospective study

    Directory of Open Access Journals (Sweden)

    Larsen Claus F

    2011-10-01

    Full Text Available Abstract Background Severe injury induces an acute coagulopathy associated with increased mortality. This study compared the Thrombelastography (TEG and biomarker profiles upon admission in trauma patients. Methods Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry including standard coagulation tests, hematology, transfusions, Injury Severity Score (ISS and TEG were recorded. Retrospective analysis of thawed plasma/serum for biomarkers reflecting tissue injury (histone-complexed DNA fragments, sympathoadrenal activation (adrenaline, noradrenaline, coagulation activation/inhibition and fibrinolysis (sCD40L, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer, prothrombinfragment 1+2, plasmin/α2-antiplasmin complex, thrombin/antithrombin complex, tissue factor pathway inhibitor, antithrombin, von willebrand factor, factor XIII. Comparison of patients stratified according to ISS/TEG maximum clot strength. Linear regression analysis of variables associated with clot strength. Results Trauma patients had normal (86%, hypercoagulable (11% or hypocoagulable (1% TEG clot strength; one had primary hyperfibrinolysis. Hypercoagulable patients had higher age, fibrinogen and platelet count (all p 10 red blood cells the initial 24 h. Patients with normal or hypercoagulable TEG clot strength had comparable biomarker profiles, but the few patients with hypocoagulable TEG clot strength and/or hyperfibrinolysis had very different biomarker profiles. Increasing ISS was associated with higher levels of catecholamines, histone-complexed DNA fragments, sCD40L, activated protein C and D-dimer and reduced levels of non-activated protein C, antithrombin, fibrinogen and factor XIII (all p 26. In patients with ISS > 26, adrenaline and sCD40L were independently negatively associated with clot strength. Conclusions Trauma patients displayed

  8. Study on comprehensive evaluation methods for nuclear fuel cycle

    International Nuclear Information System (INIS)

    Arie, Kazuo

    1999-03-01

    This investigation on comprehensive-evaluation-methods for nuclear fuel cycle has been performed through open-literature search. As the results, no proper comprehensive-evaluation-method has been found which integrate several factors to be considered into only one factor. In the evaluation of future advanced nuclear energy systems, it is required to evaluate from both view points of natural resources and natural environment, in addition to the other factors such as safety, economy, and proliferation resistance. It is recommended that clarification of specific items or targets to be evaluated is most important as the first thing to be done. Second, methodology for the evaluation should be discussed. (author)

  9. Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study.

    Science.gov (United States)

    Nickolas, Thomas L; Schmidt-Ott, Kai M; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C; Barasch, Jonathan

    2012-01-17

    This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg

    2015-01-01

    BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps...... in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

  11. A comprehensive study of benzene concentrations and emissions in Houston

    Science.gov (United States)

    Müller, Markus; Eichler, Philipp; Berk Knighton, W.; Estes, Mark; Crawford, James H.; Mikoviny, Tomas; Wisthaler, Armin

    2014-05-01

    The Houston Metropolitan Area (Greater Houston) has a population of over 6 million people, it ranks among the three fastest growing metropolises in the developed world and population growth scenarios predict it to reach megacity status in the coming two to four decades. Greater Houston is home to the largest petrochemical-manufacturing complex in the world with important consequences for the environment in the region. Direct and fugitive emissions of hydrocarbons adversely affect Houston's air quality which has been subject to intense studies over the past two decades. In 2013, NASA conducted the DISCOVER-AQ field campaign in support of developing a satellite-based capability to assess Houston's air quality in the future. Amongst other measurements, airborne, mobile ground-based and stationary ground-based measurements of benzene were carried out. Benzene is a carcinogenic air toxic with strict exposure regulations in the U.S. and in Europe. We have used the obtained comprehensive dataset to map benzene concentrations in the Houston metropolitan area, locate and identify point sources, compare industrial and traffic emissions and put them in relation to previous measurements and emission inventories. The obtained data will allow a better assessment of health risks associated with benzene exposure in a large metropolitan area that includes both traffic and industrial benzene sources. This work was funded by BMVIT / FFG-ALR in the frame of the Austrian Space Application Programme (ASAP 8, project 833451). PE was funded through the PIMMS ITN (EU-FP7, agreement number 287382). Additional resources were provided through NASA's Earth Venture program (EV-1) and the NASA Postdoctoral Program (NPP). We want to thank Scott Herndon and Aerodyne Research for their support.

  12. Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study.

    Science.gov (United States)

    Daan, Nadine M P; Koster, Maria P H; de Wilde, Marlieke A; Dalmeijer, Gerdien W; Evelein, Annemieke M V; Fauser, Bart C J M; de Jager, Wilco

    2016-01-01

    To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. Cross-sectional comparison of serum biomarkers. University Medical Center Utrecht. Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6-8 years), and a paedriatic reference population (n = 30). Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1), growth factors (PIGF, VEGF, sVEGF-R1), soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106), and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S). Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100). The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219) and adiponectin (R2 = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory biomarkers (MMP-9, S100A8) were increased, suggesting that these children may exhibit increased chronic low-grade inflammation. Additional research is required to confirm results of the current exploratory investigation.

  13. Preliminary Study of Plasma Exosomal Tau as a Potential Biomarker for Chronic Traumatic Encephalopathy.

    Science.gov (United States)

    Stern, Robert A; Tripodis, Yorghos; Baugh, Christine M; Fritts, Nathan G; Martin, Brett M; Chaisson, Christine; Cantu, Robert C; Joyce, James A; Shah, Sahil; Ikezu, Tsuneya; Zhang, Jing; Gercel-Taylor, Cicek; Taylor, Douglas D

    2016-01-01

    Chronic traumatic encephalopathy (CTE) is a tauopathy associated with prior exposure to repetitive head impacts, such as those incurred through American football and other collision sports. Diagnosis is made through neuropathological examination. Many of the clinical features of CTE are common in the general population, with and without a history of head impact exposure, making clinical diagnosis difficult. As is now common in the diagnosis of other neurodegenerative disorders, such as Alzheimer's disease, there is a need for methods to diagnose CTE during life through objective biomarkers. The aim of this study was to examine tau-positive exosomes in plasma as a potential CTE biomarker. Subjects were 78 former National Football League (NFL) players and 16 controls. Extracellular vesicles were isolated from plasma. Fluorescent nanoparticle tracking analysis was used to determine the number of vesicles staining positive for tau. The NFL group had higher exosomal tau than the control group (p <  0.0001). Exosomal tau discriminated between the groups, with 82% sensitivity, 100% specificity, 100% positive predictive value, and 53% negative predictive value. Within the NFL group, higher exosomal tau was associated with worse performance on tests of memory (p = 0.0126) and psychomotor speed (p = 0.0093). These preliminary findings suggest that exosomal tau in plasma may be an accurate, noninvasive CTE biomarker.

  14. Utility of CSF biomarkers in psychiatric disorders: a national multicentre prospective study.

    Science.gov (United States)

    Paquet, Claire; Magnin, Eloi; Wallon, David; Troussière, Anne-Cécile; Dumurgier, Julien; Jager, Alain; Bellivier, Frank; Bouaziz-Amar, Elodie; Blanc, Frédéric; Beaufils, Emilie; Miguet-Alfonsi, Carole; Quillard, Muriel; Schraen, Susanna; Pasquier, Florence; Hannequin, Didier; Robert, Philippe; Hugon, Jacques; Mouton-Liger, François

    2016-06-13

    Affective and psychotic disorders are mental or behavioural patterns resulting in an inability to cope with life's ordinary demands and routines. These conditions can be a prodromal event of Alzheimer's disease (AD). The prevalence of underlying AD lesions in psychiatric diseases is unknown, and it would be helpful to determine them in patients. AD cerebrospinal fluid (CSF) biomarkers (amyloid β, tau and phosphorylated tau) have high diagnostic accuracy, both for AD with dementia and to predict incipient AD (mild cognitive impairment due to AD), and they are sometimes used to discriminate psychiatric diseases from AD. Our objective in the present study was to evaluate the clinical utility of CSF biomarkers in a group of patients with psychiatric disease as the main diagnosis. In a multicentre prospective study, clinicians filled out an anonymous questionnaire about all of their patients who had undergone CSF biomarker evaluation. Before and after CSF biomarker results were obtained, clinicians provided a diagnosis with their level of confidence and information about the treatment. We included patients with a psychiatric disorder as the initial diagnosis. In a second part of the study conducted retrospectively in a followed subgroup, clinicians detailed the psychiatric history and we classified patients into three categories: (1) psychiatric symptoms associated with AD, (2) dual diagnosis and (3) cognitive decline not linked to a neurodegenerative disorder. Of 957 patients, 69 had an initial diagnosis of a psychiatric disorder. Among these 69 patients, 14 (20.2 %) had a CSF AD profile, 5 (7.2 %) presented with an intermediate CSF profile and 50 (72.4 %) had a non-AD CSF profile. Ultimately, 13 (18.8 %) patients were diagnosed with AD. We show that in the AD group psychiatric symptoms occurred later and the delay between the first psychiatric symptoms and the cognitive decline was shorter. This study revealed that about 20 % of patients with a primary

  15. Characterization of regional left ventricular function in nonhuman primates using magnetic resonance imaging biomarkers: a test-retest repeatability and inter-subject variability study.

    Directory of Open Access Journals (Sweden)

    Smita Sampath

    Full Text Available Pre-clinical animal models are important to study the fundamental biological and functional mechanisms involved in the longitudinal evolution of heart failure (HF. Particularly, large animal models, like nonhuman primates (NHPs, that possess greater physiological, biochemical, and phylogenetic similarity to humans are gaining interest. To assess the translatability of these models into human diseases, imaging biomarkers play a significant role in non-invasive phenotyping, prediction of downstream remodeling, and evaluation of novel experimental therapeutics. This paper sheds insight into NHP cardiac function through the quantification of magnetic resonance (MR imaging biomarkers that comprehensively characterize the spatiotemporal dynamics of left ventricular (LV systolic pumping and LV diastolic relaxation. MR tagging and phase contrast (PC imaging were used to quantify NHP cardiac strain and flow. Temporal inter-relationships between rotational mechanics, myocardial strain and LV chamber flow are presented, and functional biomarkers are evaluated through test-retest repeatability and inter subject variability analyses. The temporal trends observed in strain and flow was similar to published data in humans. Our results indicate a dominant dimension based pumping during early systole, followed by a torsion dominant pumping action during late systole. Early diastole is characterized by close to 65% of untwist, the remainder of which likely contributes to efficient filling during atrial kick. Our data reveal that moderate to good intra-subject repeatability was observed for peak strain, strain-rates, E/circumferential strain-rate (CSR ratio, E/longitudinal strain-rate (LSR ratio, and deceleration time. The inter-subject variability was high for strain dyssynchrony, diastolic strain-rates, peak torsion and peak untwist rate. We have successfully characterized cardiac function in NHPs using MR imaging. Peak strain, average systolic strain

  16. Amyloid-β peptides and tau protein as biomarkers in cerebrospinal and interstitial fluid following traumatic brain injury: A review of experimental and clinical studies

    Directory of Open Access Journals (Sweden)

    Parmenion P. Tsitsopoulos

    2013-06-01

    Full Text Available Traumatic brain injury (TBI survivors frequently suffer from life-long deficits in cognitive functions and a reduced quality of life. Axonal injury, observed in most severe TBI patients, results in accumulation of amyloid precursor protein (APP. Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ peptides, a hallmark finding in Alzheimer’s disease (AD. At autopsy, brains of AD and a subset of TBI victims display some similarities including accumulation of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. Most epidemiological evidence suggests a link between TBI and AD, implying that TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as biomarkers in interstitial fluid (ISF using cerebral microdialysis and/or cerebrospinal fluid (CSF following clinical TBI. In the present review, the available clinical and experimental literature on Aβ peptides and tau as potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and ISF tau protein levels have been observed following severe TBI and suggested to correlate with clinical outcome. Although Aβ peptides are produced by normal neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to neuronal activity and/or the presence of axonal injury. The heterogeneity of animal models, clinical cohorts, analytical techniques and the complexity of TBI in available studies make the clinical value of tau and Aβ as biomarkers uncertain at present. Additionally, the link between early post-injury changes in tau and Aβ peptides and the future risk of developing AD remains unclear. Future studies using e.g. rapid biomarker sampling combined with enhanced analytical techniques and/or novel pharmacological tools could provide additional information on the importance of Aβ peptides and tau protein in both the acute pathophysiology and long

  17. Improving the quality of biomarker candidates in untargeted metabolomics via peak table-based alignment of comprehensive two-dimensional gas chromatography-mass spectrometry data

    Science.gov (United States)

    Bean, Heather D.; Hill, Jane E.; Dimandja, Jean-Marie D.

    2015-01-01

    The potential of high-resolution analytical technologies like GC×GC/TOF MS in untargeted metabolomics and biomarker discovery has been limited by the development of fully automated software that can efficiently align and extract information from multiple chromatographic data sets. In this work we report the first investigation on a peak-by-peak basis of the chromatographic factors that impact GC×GC data alignment. A representative set of 16 compounds of different chromatographic characteristics were followed through the alignment of 63 GC×GC chromatograms. We found that varying the mass spectral match parameter had a significant influence on the alignment for poorly- resolved peaks, especially those at the extremes of the detector linear range, and no influence on well- chromatographed peaks. Therefore, optimized chromatography is required for proper GC×GC data alignment. Based on these observations, a workflow is presented for the conservative selection of biomarker candidates from untargeted metabolomics analyses. PMID:25857541

  18. Plasma Nervonic Acid Is a Potential Biomarker for Major Depressive Disorder: A Pilot Study.

    Science.gov (United States)

    Kageyama, Yuki; Kasahara, Takaoki; Nakamura, Takemichi; Hattori, Kotaro; Deguchi, Yasuhiko; Tani, Munehide; Kuroda, Kenji; Yoshida, Sumiko; Goto, Yu-Ichi; Inoue, Koki; Kato, Tadafumi

    2018-03-01

    Diagnostic biomarkers of major depressive disorder, bipolar disorder, and schizophrenia are urgently needed, because none are currently available. We performed a comprehensive metabolome analysis of plasma samples from drug-free patients with major depressive disorder (n=9), bipolar disorder (n=6), schizophrenia (n=17), and matched healthy controls (n=19) (cohort 1) using liquid chromatography time-of-flight mass spectrometry. A significant effect of diagnosis was found for 2 metabolites: nervonic acid and cortisone, with nervonic acid being the most significantly altered. The reproducibility of the results and effects of psychotropic medication on nervonic acid were verified in cohort 2, an independent sample set of medicated patients [major depressive disorder (n=45), bipolar disorder (n=71), schizophrenia (n=115)], and controls (n=90) using gas chromatography time-of-flight mass spectrometry. The increased levels of nervonic acid in patients with major depressive disorder compared with controls and patients with bipolar disorder in cohort 1 were replicated in the independent sample set (cohort 2). In cohort 2, plasma nervonic acid levels were also increased in the patients with major depressive disorder compared with the patients with schizophrenia. In cohort 2, nervonic acid levels were increased in the depressive state in patients with major depressive disorder compared with the levels in the remission state in patients with major depressive disorder and the depressive state in patients with bipolar disorder. These results suggested that plasma nervonic acid is a good candidate biomarker for the depressive state of major depressive disorder. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  19. Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke

    OpenAIRE

    Hecht, S

    2004-01-01

    Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts.

  20. [Self-esteem and giftedness: a Rorschach Comprehensive System study].

    Science.gov (United States)

    Kostogianni, N; Andronikof, A

    2014-02-01

    According to empirical literature, low self-esteem is highly correlated to behavioural and emotional problems in gifted children and adolescents. Since self-esteem is an indicator of social and emotional adjustment, it would be interesting to better understand the meaning of this construct, as it is evaluated explicitly with the use of self-report questionnaires. In order to explore the psychological processes underlying the explicit self-esteem, we studied the relation of a self-report questionnaire and an indirect measure of self and interpersonal perception using the Rorschach Comprehensive System (CS). The participants were 93 children, aged between 9 and 15 years old, with an IQ≥130. They were attending regular classes (no curriculum difference). Self-esteem was evaluated using the Coopersmith Self-Esteem Inventory (SEI). We used the Rorschach CS measures of self and interpersonal perception. The results showed no significant correlation between self-esteem and high IQ. A negative correlation between self-esteem evaluated on the SEI and the Rorschach Vista responses was found, which reflected self-critical introspection and painful self-appraisal. Then a positive correlation was observed between self-esteem and reflection answers on the Rorschach (Fr+rF>0), which are related to narcissistic-like features of personality. We also found a positive correlation between self-esteem and the Rorschach egocentricity index (EGO), which provides an estimate of self-concern. Finally, the strongest correlation was found between self-esteem and the dominance of good over poor human representations (GHR>PHR), which reveals effective interpersonal behaviour. The psychological processes which seem to be related to low self-esteem in gifted children and adolescents are maladaptive interpersonal behaviours, painful experience of introspection focusing on perceived negative aspects of the self, absence of narcissistic-like features of the personality and low self-concern. These

  1. Comprehensive Study of Acute Effects and Recovery After Concussion

    Science.gov (United States)

    2017-10-01

    Prevent Mouthguard sensor system (Cleveland Clinic) demonstrated an ability to collect true positive head impacts, verified using video evidence...comparison of HIT System data to Prevent mouthguard data with comprehensive video analysis of all collected head impacts. • Interim anlaysis of HIM...presentation in both athlete and civilian mTBI patients and (2) test hypotheses regarding sex differences in mTBI phenotypes. The project will 33 be

  2. Comprehensive aerodynamic and dynamic study of independence of ukraine monument

    Directory of Open Access Journals (Sweden)

    I. M. Lebedich

    2003-06-01

    Full Text Available Comprehensive approach for solution the engineering problems o f creation the high-rise extended pillartype Monument in Kiyv is described. The results o f dynamic tests o f 1:25 scale model and aerodynamictests o f 1:8 scale model o f the Monument in TAD-2 wind tunnel are given. The procedures fordetermination o f actual dynamic characteristics and assurance the efficiency o f damping on the siteare described

  3. QRAC-the-Code: a comprehension monitoring strategy for middle school social studies textbooks.

    Science.gov (United States)

    Berkeley, Sheri; Riccomini, Paul J

    2013-01-01

    Requirements for reading and ascertaining information from text increase as students advance through the educational system, especially in content-rich classes; hence, monitoring comprehension is especially important. However, this is a particularly challenging skill for many students who struggle with reading comprehension, including students with learning disabilities. A randomized pre-post experimental design was employed to investigate the effectiveness of a comprehension monitoring strategy (QRAC-the-Code) for improving the reading comprehension of 323 students in grades 6 and 7 in inclusive social studies classes. Findings indicated that both general education students and students with learning disabilities who were taught a simple comprehension monitoring strategy improved their comprehension of textbook content compared to students who read independently and noted important points. In addition, students in the comprehension monitoring condition reported using more reading strategies after the intervention. Implications for research and practice are discussed.

  4. Searching for new biomarkers in ovarian cancer patients: Rationale and design of a retrospective study under the Mermaid III project

    Directory of Open Access Journals (Sweden)

    Julie L. Hentze

    2017-12-01

    A thorough investigation of biomarkers in ovarian cancer, including large numbers of different markers, has never been done before. Besides from improving diagnosis and treatment, other outcomes could be markers for screening, knowledge of the molecular aspects of cancer and the discovery of new drugs. Moreover, biomarkers are a prerequisite for the development of precision medicine. This study will attack the ovarian cancer problem from several angles, thereby increasing the chance of successfully contributing to saving lives.

  5. Building a gold standard to construct search filters: a case study with biomarkers for oral cancer.

    Science.gov (United States)

    Frazier, John J; Stein, Corey D; Tseytlin, Eugene; Bekhuis, Tanja

    2015-01-01

    To support clinical researchers, librarians and informationists may need search filters for particular tasks. Development of filters typically depends on a "gold standard" dataset. This paper describes generalizable methods for creating a gold standard to support future filter development and evaluation using oral squamous cell carcinoma (OSCC) as a case study. OSCC is the most common malignancy affecting the oral cavity. Investigation of biomarkers with potential prognostic utility is an active area of research in OSCC. The methods discussed here should be useful for designing quality search filters in similar domains. The authors searched MEDLINE for prognostic studies of OSCC, developed annotation guidelines for screeners, ran three calibration trials before annotating the remaining body of citations, and measured inter-annotator agreement (IAA). We retrieved 1,818 citations. After calibration, we screened the remaining citations (n = 1,767; 97.2%); IAA was substantial (kappa = 0.76). The dataset has 497 (27.3%) citations representing OSCC studies of potential prognostic biomarkers. The gold standard dataset is likely to be high quality and useful for future development and evaluation of filters for OSCC studies of potential prognostic biomarkers. The methodology we used is generalizable to other domains requiring a reference standard to evaluate the performance of search filters. A gold standard is essential because the labels regarding relevance enable computation of diagnostic metrics, such as sensitivity and specificity. Librarians and informationists with data analysis skills could contribute to developing gold standard datasets and subsequent filters tuned for their patrons' domains of interest.

  6. Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED)

    Science.gov (United States)

    A study to comprehensively assess biomarkers of risk for progressive cervical neoplasia, and thus develop a new set of biomarkers that can distinguish those at highest risk of cervical cancer from those with benign infection

  7. Biomarkers in molecular epidemiology study of oral squamous cell carcinoma in the era of precision medicine

    Directory of Open Access Journals (Sweden)

    Qing-Hao Zhu

    2017-01-01

    Full Text Available Oral cancer, which occurs in the mouth, lips, and tongue, is a multifactorial disease whose etiology involves environment, genetic, and epigenetic factors. Tobacco use and alcohol consumption are regarded as the primary risk factors for oral squamous cell carcinoma (OSCC, and betel use, other chemicals, radiation, environmental, and genetics are reported as relevant risk factors for oral carcinogenesis. The human papillomavirus infection is an independent risk factor. Traditional epidemiology studies have revealed that environmental carcinogens are risk factors for OSCC. Molecular epidemiology studies have revealed that the susceptibility to OSCC is influenced by both environmental and genetic risk factors. However, the details and mechanisms of risk factors involved in OSCC are unclear. Advanced methods and techniques used in human genome studies provide great opportunities for researchers to explore and identify (a the details of such risk factors and (b genetic susceptibility involved in OSCC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era into the era of genome-wide association study. In the era of precision medicine, molecular epidemiology studies should focus on biomarkers for cancer genomics and their potential utility in clinical practice. Here, we briefly reviewed several molecular epidemiology studies of OSCC, focusing on biomarkers as valuable utility in risk assessment, clinical screening, diagnosis, and prognosis prediction of OSCC in the era of precision medicine.

  8. A comprehensive experimental and modeling study of isobutene oxidation

    KAUST Repository

    Zhou, Chong-Wen

    2016-03-17

    Isobutene is an important intermediate in the pyrolysis and oxidation of higher-order branched alkanes, and it is also a component of commercial gasolines. To better understand its combustion characteristics, a series of ignition delay time (IDT) and laminar flame speed (LFS) measurements have been performed. In addition, flow reactor speciation data recorded for the pyrolysis and oxidation of isobutene is also reported. Predictions of an updated kinetic model described herein are compared with each of these data sets, as well as with existing jet-stirred reactor (JSR) species measurements. IDTs of isobutene oxidation were measured in four different shock tubes and in two rapid compression machines (RCMs) under conditions of relevance to practical combustors. The combination of shock tube and RCM data greatly expands the range of available validation data for isobutene oxidation models to pressures of 50 atm and temperatures in the range 666–1715 K. Isobutene flame speeds were measured experimentally at 1 atm and at unburned gas temperatures of 298–398 K over a wide range of equivalence ratios. For the flame speed results, there was good agreement between different facilities and the current model in the fuel-rich region. Ab initio chemical kinetics calculations were carried out to calculate rate constants for important reactions such as H-atom abstraction by hydroxyl and hydroperoxyl radicals and the decomposition of 2-methylallyl radicals. A comprehensive chemical kinetic mechanism has been developed to describe the combustion of isobutene and is validated by comparison to the presently considered experimental measurements. Important reactions, highlighted via flux and sensitivity analyses, include: (a) hydrogen atom abstraction from isobutene by hydroxyl and hydroperoxyl radicals, and molecular oxygen; (b) radical–radical recombination reactions, including 2-methylallyl radical self-recombination, the recombination of 2-methylallyl radicals with

  9. Biomarkers of histone deacetylase inhibitor activity in a phase 1 combined-modality study with radiotherapy.

    Directory of Open Access Journals (Sweden)

    Anne Hansen Ree

    Full Text Available Following the demonstration that histone deacetylase inhibitors enhanced experimental radiation-induced clonogenic suppression, the Pelvic Radiation and Vorinostat (PRAVO phase 1 study, combining fractionated radiotherapy with daily vorinostat for pelvic carcinoma, was designed to evaluate both clinical and novel biomarker endpoints, the latter relating to pharmacodynamic indicators of vorinostat action in clinical radiotherapy.Potential biomarkers of vorinostat radiosensitizing action, not simultaneously manifesting molecular perturbations elicited by the radiation itself, were explored by gene expression array analysis of study patients' peripheral blood mononuclear cells (PBMC, sampled at baseline (T0 and on-treatment two and 24 hours (T2 and T24 after the patients had received vorinostat.This strategy revealed 1,600 array probes that were common for the comparisons T2 versus T0 and T24 versus T2 across all of the patients, and furthermore, that no significantly differential expression was observed between the T0 and T24 groups. Functional annotation analysis of the array data showed that a significant number of identified genes were implicated in gene regulation, the cell cycle, and chromatin biology. Gene expression was validated both in patients' PBMC and in vorinostat-treated human carcinoma xenograft models, and transient repression of MYC was consistently observed.Within the design of the PRAVO study, all of the identified genes showed rapid and transient induction or repression and therefore, in principle, fulfilled the requirement of being pharmacodynamic biomarkers of vorinostat action in fractionated radiotherapy, possibly underscoring the role of MYC in this therapeutic setting.

  10. A Systematic Review of Longitudinal Studies Which Measure Alzheimer's Disease Biomarkers.

    Science.gov (United States)

    Lawrence, Emma; Vegvari, Carolin; Ower, Alison; Hadjichrysanthou, Christoforos; De Wolf, Frank; Anderson, Roy M

    2017-01-01

    Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease, with no effective treatment or cure. A gold standard therapy would be treatment to slow or halt disease progression; however, knowledge of causation in the early stages of AD is very limited. In order to determine effective endpoints for possible therapies, a number of quantitative surrogate markers of disease progression have been suggested, including biochemical and imaging biomarkers. The dynamics of these various surrogate markers over time, particularly in relation to disease development, are, however, not well characterized. We reviewed the literature for studies that measured cerebrospinal fluid or plasma amyloid-β and tau, or took magnetic resonance image or fluorodeoxyglucose/Pittsburgh compound B-positron electron tomography scans, in longitudinal cohort studies. We summarized the properties of the major cohort studies in various countries, commonly used diagnosis methods and study designs. We have concluded that additional studies with repeat measures over time in a representative population cohort are needed to address the gap in knowledge of AD progression. Based on our analysis, we suggest directions in which research could move in order to advance our understanding of this complex disease, including repeat biomarker measurements, standardization and increased sample sizes.

  11. Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and an electrochemiluminescense-based multi-array platform.

    Directory of Open Access Journals (Sweden)

    Bas C T van Bussel

    Full Text Available BACKGROUND: In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. METHODS: We measured, in a large ongoing cohort study (n = 574, by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD and single-biomarker techniques (ELISA or immunoturbidimetric assay, the following biomarkers of low-grade inflammation: C-reactive protein (CRP, serum amyloid A (SAA, soluble intercellular adhesion molecule 1 (sICAM-1 and soluble vascular cell adhesion molecule 1 (sVCAM-1. These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects' cardiovascular risk factors by ANOVA. RESULTS: Despite that both methods ranked individuals' levels of biomarkers very similarly (Pearson's r all≥0.755 absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP, 0.711 (SAA, 0.895 (sICAM-1 and 0.858 (sVCAM-1. Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method. CONCLUSIONS: Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies.

  12. Improving the quality of biomarker candidates in untargeted metabolomics via peak table-based alignment of comprehensive two-dimensional gas chromatography-mass spectrometry data.

    Science.gov (United States)

    Bean, Heather D; Hill, Jane E; Dimandja, Jean-Marie D

    2015-05-15

    The potential of high-resolution analytical technologies like GC×GC/TOF MS in untargeted metabolomics and biomarker discovery has been limited by the development of fully automated software that can efficiently align and extract information from multiple chromatographic data sets. In this work we report the first investigation on a peak-by-peak basis of the chromatographic factors that impact GC×GC data alignment. A representative set of 16 compounds of different chromatographic characteristics were followed through the alignment of 63 GC×GC chromatograms. We found that varying the mass spectral match parameter had a significant influence on the alignment for poorly-resolved peaks, especially those at the extremes of the detector linear range, and no influence on well-chromatographed peaks. Therefore, optimized chromatography is required for proper GC×GC data alignment. Based on these observations, a workflow is presented for the conservative selection of biomarker candidates from untargeted metabolomics analyses. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Lichen biomarkers upon heating: a Raman spectroscopic study with implications for extra-terrestrial exploration

    Science.gov (United States)

    Miralles, I.; Capel Ferrón, C.; Hernández, V.; López-Navarrete, J. T.; Jorge-Villar, S. E.

    2017-01-01

    Lithopanspermia Theory has suggested that life was transferred among planets by meteorites and other rocky bodies. If the planet had an atmosphere, this transfer of life had to survive drastic temperature changes in a very short time in its entry or exit. Only organisms able to endure such a temperature range could colonize a planet from outer space. Many experiments are being carried out by NASA and European Space Agency to understand which organisms were able to survive and how. Among the suite of instruments designed for extraplanetary exploration, particularly for Mars surface exploration, a Raman spectrometer was selected with the main objective of looking for life signals. Among all attributes, Raman spectroscopy is able to identify organic and inorganic compounds, either pure or in admixture, without requiring sample manipulation. In this study, we used Raman spectroscopy to examine the lichen Squamarina lentigera biomarkers. We analyse spectral signature changes after sample heating under different experimental situations, such as (a) laser, (b) analysis accumulations over the same spot and (c) environmental temperature increase. Our goal is to evaluate the capability of Raman spectroscopy to identify unambiguously life markers even if heating has induced spectral changes, reflecting biomolecular transformations. Usnic acid, chlorophyll, carotene and calcium oxalates were identified by the Raman spectra. From our experiments, we have seen that usnic acid, carotene and calcium oxalates (the last two have been suggested to be good biomarkers) respond in a different way to environmental heating. Our main conclusion is that despite their abundance in nature or their inorganic composition the resistance to heat makes some molecules more suitable than others as biomarkers.

  14. Reciprocal Teaching and Emotional Intelligence: A Study of Iranian EFL Learners' Reading Comprehension

    Science.gov (United States)

    Izadi, Mehri; Nowrouzi, Hossein

    2016-01-01

    The present study aimed at exploring the effect of reciprocal reading strategies instruction on reading comprehension of EFL learners. Emotional intelligence, another variable of interest, was assessed to indicate whether it plays a role in learners' comprehension. In a pre- and post-test study, forty-two learners went through a reciprocal reading…

  15. The Effect of Stories for Thinking on Reading and Listening Comprehension: A Case Study in Turkey

    Science.gov (United States)

    Tok, Sükran; Mazl, Aysegül

    2015-01-01

    This study has been conducted in order to examine the effects of the stories for thinking on 5th graders' reading comprehension and listening comprehension. A pretest-post test control group quasi-experimental design was used in the study. The sample of the etstudy was composed of 74 5th graders attending public elementary schools. The data have…

  16. Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Nadine M P Daan

    Full Text Available To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring.Cross-sectional comparison of serum biomarkers.University Medical Center Utrecht.Hyperandrogenic PCOS women (HA-PCOS, n = 34, normoandrogenic PCOS women (NA-PCOS, n = 34, non-PCOS reference population (n = 32, PCOS offspring (n = 14, age 6-8 years, and a paedriatic reference population (n = 30.Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1, growth factors (PIGF, VEGF, sVEGF-R1, soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106, and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S. Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100.The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219 and adiponectin (R2 = 0.182 showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001, DPP-IV (P = 0.005, and adiponectin (P < 0.001. Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001 and S100A8 (P < 0.001 concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing.In this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory biomarkers

  17. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study.

    Science.gov (United States)

    Laskowitz, Daniel T; Kasner, Scott E; Saver, Jeffrey; Remmel, Kerri S; Jauch, Edward C

    2009-01-01

    One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit. A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach. A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform. These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a

  18. Biomarkers of oxidative stress and DNA damage in agricultural workers: A pilot study

    International Nuclear Information System (INIS)

    Muniz, Juan F.; McCauley, Linda; Scherer, J.; Lasarev, M.; Koshy, M.; Kow, Y.W.; Nazar-Stewart, Valle; Kisby, G.E.

    2008-01-01

    Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to health effects such as cancer and neurological diseases. A study of pesticide applicators and farmworkers was conducted to examine the relationship between organophosphate pesticide exposure and biomarkers of oxidative stress and DNA damage. Urine samples were analyzed for OP metabolites and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Lymphocytes were analyzed for oxidative DNA repair activity and DNA damage (Comet assay), and serum was analyzed for lipid peroxides (i.e., malondialdehyde, MDA). Cellular damage in agricultural workers was validated using lymphocyte cell cultures. Urinary OP metabolites were significantly higher in farmworkers and applicators (p < 0.001) when compared to controls. 8-OH-dG levels were 8.5 times and 2.3 times higher in farmworkers or applicators (respectively) than in controls. Serum MDA levels were 4.9 times and 24 times higher in farmworkers or applicators (respectively) than in controls. DNA damage (Comet assay) and oxidative DNA repair were significantly greater in lymphocytes from applicators and farmworkers when compared with controls. Markers of oxidative stress (i.e., increased reactive oxygen species and reduced glutathione levels) and DNA damage were also observed in lymphocyte cell cultures treated with an OP. The findings from these in vivo and in vitro studies indicate that organophosphate pesticides induce oxidative stress and DNA damage in agricultural workers. These biomarkers may be useful for increasing our understanding of the link between pesticides and a number of health effects

  19. Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies

    Science.gov (United States)

    Ostler, Michael W.; Porter, James H.; Buxton, Orfeu M.

    2014-01-01

    Biomarkers are directly-measured biological indicators of disease, health, exposures, or other biological information. In population and social sciences, biomarkers need to be easy to obtain, transport, and analyze. Dried Blood Spots meet this need, and can be collected in the field with high response rates. These elements are particularly important in longitudinal study designs including interventions where attrition is critical to avoid, and high response rates improve the interpretation of results. Dried Blood Spot sample collection is simple, quick, relatively painless, less invasive then venipuncture, and requires minimal field storage requirements (i.e. samples do not need to be immediately frozen and can be stored for a long period of time in a stable freezer environment before assay). The samples can be analyzed for a variety of different analytes, including cholesterol, C-reactive protein, glycosylated hemoglobin, numerous cytokines, and other analytes, as well as provide genetic material. DBS collection is depicted as employed in several recent studies. PMID:24513728

  20. A predictive study of reading comprehension in third-grade Spanish students.

    Science.gov (United States)

    López-Escribano, Carmen; Elosúa de Juan, María Rosa; Gómez-Veiga, Isabel; García-Madruga, Juan Antonio

    2013-01-01

    The study of the contribution of language and cognitive skills to reading comprehension is an important goal of current reading research. However, reading comprehension is not easily assessed by a single instrument, as different comprehension tests vary in the type of tasks used and in the cognitive demands required. This study examines the contribution of basic language and cognitive skills (decoding, word recognition, reading speed, verbal and nonverbal intelligence and working memory) to reading comprehension, assessed by two tests utilizing various tasks that require different skill sets in third-grade Spanish-speaking students. Linguistic and cognitive abilities predicted reading comprehension. A measure of reading speed (the reading time of pseudo-words) was the best predictor of reading comprehension when assessed by the PROLEC-R test. However, measures of word recognition (the orthographic choice task) and verbal working memory were the best predictors of reading comprehension when assessed by means of the DARC test. These results show, on the one hand, that reading speed and word recognition are better predictors of Spanish language comprehension than reading accuracy. On the other, the reading comprehension test applied here serves as a critical variable when analyzing and interpreting results regarding this topic.

  1. 'Omics' biomarkers associated with chronic low back pain: protocol of a retrospective longitudinal study.

    Science.gov (United States)

    Allegri, Massimo; De Gregori, Manuela; Minella, Cristina E; Klersy, Catherine; Wang, Wei; Sim, Moira; Gieger, Christian; Manz, Judith; Pemberton, Iain K; MacDougall, Jane; Williams, Frances Mk; Van Zundert, Jan; Buyse, Klaas; Lauc, Gordan; Gudelj, Ivan; Primorac, Dragan; Skelin, Andrea; Aulchenko, Yurii S; Karssen, Lennart C; Kapural, Leonardo; Rauck, Richard; Fanelli, Guido

    2016-10-19

    Chronic low back pain (CLBP) produces considerable direct costs as well as indirect burdens for society, industry and health systems. CLBP is characterised by heterogeneity, inclusion of several pain syndromes, different underlying molecular pathologies and interaction with psychosocial factors that leads to a range of clinical manifestations. There is still much to understand in the underlying pathological processes and the non-psychosocial factors which account for differences in outcomes. Biomarkers that may be objectively used for diagnosis and personalised, targeted and cost-effective treatment are still lacking. Therefore, any data that may be obtained at the '-omics' level (glycomics, Activomics and genome-wide association studies-GWAS) may be helpful to use as dynamic biomarkers for elucidating CLBP pathogenesis and may ultimately provide prognostic information too. By means of a retrospective, observational, case-cohort, multicentre study, we aim to investigate new promising biomarkers potentially able to solve some of the issues related to CLBP. The study follows a two-phase, 1:2 case-control model. A total of 12 000 individuals (4000 cases and 8000 controls) will be enrolled; clinical data will be registered, with particular attention to pain characteristics and outcomes of pain treatments. Blood samples will be collected to perform -omics studies. The primary objective is to recognise genetic variants associated with CLBP; secondary objectives are to study glycomics and Activomics profiles associated with CLBP. The study is part of the PainOMICS project funded by European Community in the Seventh Framework Programme. The study has been approved from competent ethical bodies and copies of approvals were provided to the European Commission before starting the study. Results of the study will be reviewed by the Scientific Board and Ethical Committee of the PainOMICS Consortium. The scientific results will be disseminated through peer-reviewed journals

  2. Biomarker Detection in Association Studies: Modeling SNPs Simultaneously via Logistic ANOVA

    KAUST Repository

    Jung, Yoonsuh; Huang, Jianhua Z.; Hu, Jianhua

    2014-01-01

    In genome-wide association studies, the primary task is to detect biomarkers in the form of Single Nucleotide Polymorphisms (SNPs) that have nontrivial associations with a disease phenotype and some other important clinical/environmental factors. However, the extremely large number of SNPs comparing to the sample size inhibits application of classical methods such as the multiple logistic regression. Currently the most commonly used approach is still to analyze one SNP at a time. In this paper, we propose to consider the genotypes of the SNPs simultaneously via a logistic analysis of variance (ANOVA) model, which expresses the logit transformed mean of SNP genotypes as the summation of the SNP effects, effects of the disease phenotype and/or other clinical variables, and the interaction effects. We use a reduced-rank representation of the interaction-effect matrix for dimensionality reduction, and employ the L 1-penalty in a penalized likelihood framework to filter out the SNPs that have no associations. We develop a Majorization-Minimization algorithm for computational implementation. In addition, we propose a modified BIC criterion to select the penalty parameters and determine the rank number. The proposed method is applied to a Multiple Sclerosis data set and simulated data sets and shows promise in biomarker detection.

  3. Saliva levels of Abeta1-42 as potential biomarker of Alzheimer's disease: a pilot study

    Directory of Open Access Journals (Sweden)

    Antequera Desiree

    2010-11-01

    Full Text Available Abstract Background Simple, non-invasive tests for early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers for the early diagnosis of Alzheimer disease (AD are available. The clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. A biochemical marker that would support the clinical diagnosis and distinguish AD from other causes of dementia would therefore be of great value as a screening test. A total of 126 samples were obtained from subjects with AD, and age-sex-matched controls. Additionally, 51 Parkinson's disease (PD patients were used as an example of another neurodegenerative disorder. We analyzed saliva and plasma levels of β amyloid (Aβ using a highly sensitive ELISA kit. Results We found a small but statistically significant increase in saliva Aβ42 levels in mild AD patients. In addition, there were not differences in saliva concentration of Aβ42 between patients with PD and healthy controls. Saliva Aβ40 expression was unchanged within all the studied sample. The association between saliva Aβ42 levels and AD was independent of established risk factors, including age or Apo E, but was dependent on sex and functional capacity. Conclusions We suggest that saliva Aβ42 levels could be considered a potential peripheral marker of AD and help discrimination from other types of neurodegenerative disorders. We propose a new and promising biomarker for early AD.

  4. Urinary metabonomics study on toxicity biomarker discovery in rats treated with Xanthii Fructus.

    Science.gov (United States)

    Lu, Fang; Cao, Min; Wu, Bin; Li, Xu-zhao; Liu, Hong-yu; Chen, Da-zhong; Liu, Shu-min

    2013-08-26

    Xanthii Fructus (XF) is commonly called "Cang-Erzi" in traditional Chinese medicine (TCM) and widely used for the treatment of sinusitis, headache, rheumatism, and skin itching. However, the clinical utilization of XF is relatively restricted owing to its toxicity. To discover the characteristic potential biomarkers in rats treated with XF by urinary metabonomics. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was applied in the study. The total ion chromatograms obtained from control and different dosage groups were distinguishable by a multivariate statistical analysis method. The greatest difference in metabolic profile was observed between high dosage group and control group, and the metabolic characters in rats treated with XF were perturbed in a dose-dependent manner. The metabolic changes in response for XF treatment were observed in urinary samples, which were revealed by orthogonal projection to latent structures discriminate analysis (OPLS-DA), and 10 metabolites could be served as the potential toxicity biomarkers. In addition, the mechanism associated with the damages of lipid per-oxidation and the metabolic disturbances of fatty acid oxidation were investigated. These results indicate that metabonomics analysis in urinary samples may be useful for predicting the toxicity induced by XF. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Biomarker Detection in Association Studies: Modeling SNPs Simultaneously via Logistic ANOVA

    KAUST Repository

    Jung, Yoonsuh

    2014-10-02

    In genome-wide association studies, the primary task is to detect biomarkers in the form of Single Nucleotide Polymorphisms (SNPs) that have nontrivial associations with a disease phenotype and some other important clinical/environmental factors. However, the extremely large number of SNPs comparing to the sample size inhibits application of classical methods such as the multiple logistic regression. Currently the most commonly used approach is still to analyze one SNP at a time. In this paper, we propose to consider the genotypes of the SNPs simultaneously via a logistic analysis of variance (ANOVA) model, which expresses the logit transformed mean of SNP genotypes as the summation of the SNP effects, effects of the disease phenotype and/or other clinical variables, and the interaction effects. We use a reduced-rank representation of the interaction-effect matrix for dimensionality reduction, and employ the L 1-penalty in a penalized likelihood framework to filter out the SNPs that have no associations. We develop a Majorization-Minimization algorithm for computational implementation. In addition, we propose a modified BIC criterion to select the penalty parameters and determine the rank number. The proposed method is applied to a Multiple Sclerosis data set and simulated data sets and shows promise in biomarker detection.

  6. A study on some enzymes in rice field fish as biomarkers for pesticide exposure

    International Nuclear Information System (INIS)

    Juzu Hayati Arshad; Mazlina Muhammad; Salmijah Surif; Abdul Manan Mat Jais

    2002-01-01

    A study was carried out on three enzymes in rice field fish which can be used as possible biomarkers for pesticide exposure. The results obtained showed that the activity of the enzyme EROD (ethoxyresorufin-o-deethylase) increased between 1.5-2.2 fold in snakehead or haruan (Channa striata) sampled from the pesticide polluted areas, particularly the recycled areas and only a slight increase in EROD activity in climbing perch or puyu (Anabas testudineus). Increase in the activity of carboxylesterase was also noted. The percentage inhibition of acety1cholinesterase ranges from 18.4%-57.4% and 2.5%-34.2% for Channa striata and Anabas testudineus, respectively. Generally, a higher percentage of acety1cholinesterase inhibition was noted for those fish sampled from the recycled areas. The noted changes in the activity of these enzymes suggest exposure of rice field fish to foreign compounds, possibly pesticides, which are known to induce EROD activity and inhibit acety1cholinesterase activity. Therefore it may be possible to use these enzymes as biomarkers for pesticide exposure. (Author)

  7. Effects of Audiovisual Media on L2 Listening Comprehension: A Preliminary Study in French

    Science.gov (United States)

    Becker, Shannon R.; Sturm, Jessica L.

    2017-01-01

    The purpose of the present study was to determine whether integrating online audiovisual materials into the listening instruction of L2 French learners would have a measurable impact on their listening comprehension development. Students from two intact sections of second-semester French were tested on their listening comprehension before and…

  8. Study on supporting system for operator's comprehensive understanding

    International Nuclear Information System (INIS)

    Yoshikawa, Shinji

    1996-01-01

    Power Reactor and Nuclear Fuel Development Corp. has participated in the development of a system to support the process of operator's plant understanding by the use of information processing techniques such as artificial intelligence since 1994. Analysis and model formation of the process leading to operator's comprehensive understanding of plant (mental model) are undertaken attempting to determine the basic structure of the mental model available for the description of knowledge using the precedent survey and to observe how to utilize operator's own knowledge. After consideration of the way by which plant operators utilize their physical knowledges and the knowledges of physical observation in practice, a basic structure composed of 3 components a qualitative causal network, a hierarchical function model and 3 links joining the two was proposed for the mental model. A questionnaire survey on operator's statements was made and the contents were assigned in several categories for objective analysis. An unified form usable to make a data base was established. Further, we have a plan to develop the first proto-type system to promote operator's understanding by 1998. (M.N.)

  9. Comprehensive Study on Lexicon-based Ensemble Classification Sentiment Analysis

    Directory of Open Access Journals (Sweden)

    Łukasz Augustyniak

    2015-12-01

    Full Text Available We propose a novel method for counting sentiment orientation that outperforms supervised learning approaches in time and memory complexity and is not statistically significantly different from them in accuracy. Our method consists of a novel approach to generating unigram, bigram and trigram lexicons. The proposed method, called frequentiment, is based on calculating the frequency of features (words in the document and averaging their impact on the sentiment score as opposed to documents that do not contain these features. Afterwards, we use ensemble classification to improve the overall accuracy of the method. What is important is that the frequentiment-based lexicons with sentiment threshold selection outperform other popular lexicons and some supervised learners, while being 3–5 times faster than the supervised approach. We compare 37 methods (lexicons, ensembles with lexicon’s predictions as input and supervised learners applied to 10 Amazon review data sets and provide the first statistical comparison of the sentiment annotation methods that include ensemble approaches. It is one of the most comprehensive comparisons of domain sentiment analysis in the literature.

  10. Comprehensive study of tartrazine/cationic surfactant interaction.

    Science.gov (United States)

    Shahir, Afshin Asadzadeh; Javadian, Soheila; Razavizadeh, Bi Bi Marzieh; Gharibi, Hussein

    2011-12-15

    Interaction of a food dye, tartrazine, with some cationic conventional and gemini surfactants, tetradecyltrimethylammonium bromide (TTAB), N,N'-ditetradecyl-N,N,N',N'-tetramethyl-N,N'-butanediyl-diammonium dibromide (14,4,14), and N,N'-didodecyl-N,N,N',N'-tetramethyl-N,N'-butanediyl-diammonium dibromide (12,4,12), were first investigated comprehensively employing conductometry, tensiometry, and UV-visible spectroscopy. Tartrazine was found to behave in the same manner as aromatic counterions. The formation of ion pairs reflected as a considerable increase of the surfactant efficiency in tensiometry plots and their stoichiometry were determined by Job's method of continuous variations. For the tartrazine/TTAB system, nonionic DS(3), ionic DS(2-), and/or DS(2)(-) ion pairs, their small premicelles, and tartrazine-rich micelles were constituted as well as dye-containing TTAB-rich micelles. Insoluble J-aggregates of DS(-) ion pairs and cylindrical surfactant-rich micelles were also formed in tartrazine/gemini surfactant systems and recognized by transmission electron microscopy. The zeta potential and the size of the aggregates were determined using dynamic light scattering and confirmed the suggested models for the processes happening in each system. Cyclic voltammetry was applied successfully to track all of these species using tartrazine's own reduction peak current for the first time.

  11. Simulation of complex data structures for planning of studies with focus on biomarker comparison.

    Science.gov (United States)

    Schulz, Andreas; Zöller, Daniela; Nickels, Stefan; Beutel, Manfred E; Blettner, Maria; Wild, Philipp S; Binder, Harald

    2017-06-13

    There are a growing number of observational studies that do not only focus on single biomarkers for predicting an outcome event, but address questions in a multivariable setting. For example, when quantifying the added value of new biomarkers in addition to established risk factors, the aim might be to rank several new markers with respect to their prediction performance. This makes it important to consider the marker correlation structure for planning such a study. Because of the complexity, a simulation approach may be required to adequately assess sample size or other aspects, such as the choice of a performance measure. In a simulation study based on real data, we investigated how to generate covariates with realistic distributions and what generating model should be used for the outcome, aiming to determine the least amount of information and complexity needed to obtain realistic results. As a basis for the simulation a large epidemiological cohort study, the Gutenberg Health Study was used. The added value of markers was quantified and ranked in subsampling data sets of this population data, and simulation approaches were judged by the quality of the ranking. One of the evaluated approaches, the random forest, requires original data at the individual level. Therefore, also the effect of the size of a pilot study for random forest based simulation was investigated. We found that simple logistic regression models failed to adequately generate realistic data, even with extensions such as interaction terms or non-linear effects. The random forest approach was seen to be more appropriate for simulation of complex data structures. Pilot studies starting at about 250 observations were seen to provide a reasonable level of information for this approach. We advise to avoid oversimplified regression models for simulation, in particular when focusing on multivariable research questions. More generally, a simulation should be based on real data for adequately reflecting

  12. Ethics and data protection in human biomarker studies in environmental health.

    Science.gov (United States)

    Casteleyn, Ludwine; Dumez, Birgit; Van Damme, Karel; Anwar, Wagida A

    2013-08-01

    Human biomarker studies in environmental health are essential tools to study the relationship between health and environment. They should ultimately contribute to a better understanding of environmentally induced adverse health effects and to appropriate preventive actions. To ensure the protection of the rights and dignity of study participants a complex legal and ethical framework is applied, consisting of several international directives, conventions, and guidelines, whether or not translated in domestic laws. Main characteristics of ethics and data protection in studies using biomarkers in the field of environmental health are summarized and current discussions on related questions and bottlenecks highlighted. In the current regulatory context, dominated by the protection of the individual study participant, difficulties are reported due to the different interpretation and implementation of the regulations of concern within and across borders. Advancement of consistency and compatibility is recommended and efforts are ongoing. An increasing demand for secondary use of data and samples poses additional challenges in finding a right balance between the individual rights of the study participants on the one hand and the common interest of, and potential benefit for the public or community at large on the other. Ethics committees could play a key role in assessing problems originating from the sometimes competing needs at individual and societal level. Building trust in science amongst (potential) study participants and within the community allows the inclusion of arguments from the societal perspective. This requires increased attention for respectful communication efforts. Striving for public participation in decision making processes may promote policy relevant research and the related translation of study results into action. Copyright © 2013 Elsevier GmbH. All rights reserved.

  13. Simulation of complex data structures for planning of studies with focus on biomarker comparison

    Directory of Open Access Journals (Sweden)

    Andreas Schulz

    2017-06-01

    Full Text Available Abstract Background There are a growing number of observational studies that do not only focus on single biomarkers for predicting an outcome event, but address questions in a multivariable setting. For example, when quantifying the added value of new biomarkers in addition to established risk factors, the aim might be to rank several new markers with respect to their prediction performance. This makes it important to consider the marker correlation structure for planning such a study. Because of the complexity, a simulation approach may be required to adequately assess sample size or other aspects, such as the choice of a performance measure. Methods In a simulation study based on real data, we investigated how to generate covariates with realistic distributions and what generating model should be used for the outcome, aiming to determine the least amount of information and complexity needed to obtain realistic results. As a basis for the simulation a large epidemiological cohort study, the Gutenberg Health Study was used. The added value of markers was quantified and ranked in subsampling data sets of this population data, and simulation approaches were judged by the quality of the ranking. One of the evaluated approaches, the random forest, requires original data at the individual level. Therefore, also the effect of the size of a pilot study for random forest based simulation was investigated. Results We found that simple logistic regression models failed to adequately generate realistic data, even with extensions such as interaction terms or non-linear effects. The random forest approach was seen to be more appropriate for simulation of complex data structures. Pilot studies starting at about 250 observations were seen to provide a reasonable level of information for this approach. Conclusions We advise to avoid oversimplified regression models for simulation, in particular when focusing on multivariable research questions. More generally

  14. The study of protein biomarkers to understand the biochemical processes underlying beef color development in young bulls.

    Science.gov (United States)

    Gagaoua, Mohammed; Terlouw, E M Claudia; Picard, Brigitte

    2017-12-01

    This study investigates relationships between 21 biomarkers and meat color traits of Longissimus thoracis muscles of young Aberdeen Angus and Limousin bulls. The relationships found allowed to propose metabolic processes underlying meat color. The color coordinates were related with several biomarkers. The relationships were in some cases breed-dependent and the variability explained in the regression models varied between 31 and 56%. The correlations between biomarkers and color parameters were sometimes opposite between breeds. The PCA using the 21 biomarkers and the instrumental color coordinates showed that these variables discriminated efficiently between the two studied breeds. Results are coherent with earlier studies on other beef breeds showing that several proteins belonging to different but partly related biological pathways involved in muscle contraction, metabolism, heat stress and apoptosis are related to beef color. The results suggest that in future, biomarkers may be used to classify meat cuts sampled early post-mortem according to their forthcoming color. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Mitochondrial Biomarkers Reflect Semen Quality: Results from the MARCHS Study in Chongqing, China.

    Science.gov (United States)

    Zhang, Guowei; Wang, Zhi; Ling, Xi; Zou, Peng; Yang, Huan; Chen, Qing; Zhou, Niya; Sun, Lei; Gao, Jianfang; Zhou, Ziyuan; Cao, Jia; Ao, Lin

    2016-01-01

    Unexplained infertility requires that more sensitive and mechanism-based biomarkers should be developed and used independently of or in addition to conventional semen parameters for an infertility diagnosis. In the present study, semen samples were collected from young men participating in the Male Reproductive Health in Chongqing College students (MARCHS) cohort study in the follow-up stage in 2014. Conventional semen parameters were measured in all 656 participants, whereas sperm mitochondrial membrane potential (MMP), mitochondrial DNA copy number (mtDNAcn), mtDNA integrity and apoptotic parameters were measured among 627, 386, 362, and 628 participants, respectively. We found that sperm MMP was significantly positively correlated with all of conventional semen parameters including semen volume (r = 0.090, p = 0.025), sperm concentration (r = 0.301, psemen quality in a general population, and the study provides a baseline for the effects of population characteristics and lifestyles on such mitochondrial markers.

  16. Biomarkers in patients with Chronic Obstructive Pulmonary Disease in general practice: A prospective cohort study

    DEFF Research Database (Denmark)

    Waldorff, Frans Boch; Halling, Anders; Ledderer, Loni

    Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a common chronic disease primarily treated in primary care. It is a complex and heterogeneous disease and the trajectory is difficult to predict. The overall aim of this study is to investigate predictors of the trajectory of COPD...... were a diagnosis of COPD (ICPC code R95-), age ≥ 40 years, Danish language speaking, no severe psychiatric or cognitive disease and ability to visit the GP surgery. Prevalent as well as incident patients diagnosed with COPD were eligible. Baseline data included a patient questionnaire and validated...... treated in primary care and to determine the added value of selected biomarkers such as microfibrillar-associated protein 4 (MFAP4) and surfactant protein D (SP-D). Methods: Prospective cohort study comprising COPD patients. A total of 38 Danish practices were included in the study. Criteria for inclusion...

  17. Network-based identification of biomarkers coexpressed with multiple pathways.

    Science.gov (United States)

    Guo, Nancy Lan; Wan, Ying-Wooi

    2014-01-01

    Unraveling complex molecular interactions and networks and incorporating clinical information in modeling will present a paradigm shift in molecular medicine. Embedding biological relevance via modeling molecular networks and pathways has become increasingly important for biomarker identification in cancer susceptibility and metastasis studies. Here, we give a comprehensive overview of computational methods used for biomarker identification, and provide a performance comparison of several network models used in studies of cancer susceptibility, disease progression, and prognostication. Specifically, we evaluated implication networks, Boolean networks, Bayesian networks, and Pearson's correlation networks in constructing gene coexpression networks for identifying lung cancer diagnostic and prognostic biomarkers. The results show that implication networks, implemented in Genet package, identified sets of biomarkers that generated an accurate prediction of lung cancer risk and metastases; meanwhile, implication networks revealed more biologically relevant molecular interactions than Boolean networks, Bayesian networks, and Pearson's correlation networks when evaluated with MSigDB database.

  18. Comprehensive study on nuclear weapons. Summary of a United Nations study

    International Nuclear Information System (INIS)

    1991-01-01

    In December 1988, by resolution 43/75N, the United Nations General Assembly requested the Secretary-General to carry out a comprehensive update of a 1980 study on nuclear weapons. The study was to take into account recent relevant studies, and consider the political, legal and security aspects of: (a) nuclear arsenals and pertinent technological developments; (b) doctrines concerning nuclear weapons; (c) efforts to reduce nuclear weapons; (d) physical, environmental, medical and other effects of the use of nuclear weapons and of nuclear testing; (e) efforts to achieve a comprehensive nuclear-test ban; (f) efforts to prevent the use of nuclear weapons and their horizontal and vertical proliferation; and (g) the question of verification of compliance with nuclear-arms limitation agreements. The Group's report is presented in nine chapters, eight of which are summarized here; chapter 9, entitled ''Conclusions'', is included in its entirety. In his foreword to the report, the Secretary-General observes that the study represents the most comprehensive review of the relevant developments in the field over the last decade and was carried out during a period of ''far-reaching changes in international relations'' and an ''unprecedented evolution in the relationship between East and West''. This period experienced for the first time the initiation of an effective process of reduction of nuclear weapon stockpiles

  19. Alterations in inflammatory biomarkers and energy intake in cancer cachexia: a prospective study in patients with inoperable pancreatic cancer.

    Science.gov (United States)

    Bye, Asta; Wesseltoft-Rao, Nima; Iversen, Per Ole; Skjegstad, Grete; Holven, Kirsten B; Ulven, Stine; Hjermstad, Marianne J

    2016-06-01

    Chronic systemic inflammatory response is proposed as an underlying mechanism for development of cancer cachexia. We conducted a prospective study to examine changes in inflammatory biomarkers during the disease course and the relationship between inflammatory biomarkers and cachexia in patients with inoperable pancreatic cancer. Twenty patients, median (range) age 67.5 (35-79) years, 5 females, were followed for median 5.5 (1-12) months. Cachexia was diagnosed according to the 2011 consensus-based classification system (weight loss >5 % past six months, BMI 2 %, or sarcopenia) and the modified Glasgow Prognostic score (mGPS) that combines CRP and albumin levels. Inflammatory biomarkers were measured by enzyme immunoassays. The patients had increased levels of most inflammatory biomarkers, albeit not all statistically significant, both at study entry and close to death, indicating ongoing inflammation. According to the consensus-based classification system, eleven (55 %) patients were classified as cachectic upon inclusion. They did not differ from non-cachectic patients with regard to inflammatory biomarkers or energy intake. According to the mGPS, seven (35 %) were defined as cachectic and had a higher IL-6 (p cachexia.

  20. Serum Sclerostin as a Possible Biomarker in Ankylosing Spondylitis: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Fabio Massimo Perrotta

    2018-01-01

    Full Text Available Objective. Several molecules are involved in the pathogenesis of a new bone formation in ankylosing spondylitis (AS. The aim of this study was to evaluate the serum levels of sclerostin in patients with AS as a possible biomarker and to investigate any correlations with radiographic damage, disease activity, and function. Methods. AS patients fulfilled the modified New York criteria, and healthy controls were enrolled for this study. BASDAI, ASDAS-CRP, BASMI, BASFI, patient and physician VAS, and C-reactive protein were evaluated at baseline visit. Spinal damage was assessed using the mSASSS on radiographs performed within 3 months from baseline. Serum concentrations of sclerostin were assessed at baseline and after four months of therapy in patients who started an anti-TNF. Results. Twenty healthy subjects and 40 AS patients were enrolled in the study. In our group, serum sclerostin levels (median (25th–75th percentile were significantly higher in healthy controls (18.04 (13.6–24 pg/ml than in AS patients (6.46 (4.5–11.1 pg/ml; P value < 0.01. However, no significant correlations were found between serum sclerostin levels and radiographic damage, assessed by mSASSS, and between serum sclerostin levels and clinical indices of activity and disability or with laboratory parameters. Sclerostin levels did not show significant changes after 4 months of anti-TNF therapy. Conclusions. The results of our study suggest a possible role of sclerostin in the identification of AS patients. Further studies are needed to prove the role of sclerostin as a disease activity biomarker and progression of disease in AS.

  1. Biomarkers of Exposure to Toxic Substances. Volume 5: Biomarker Pre-validation Studies Prevalidation of Urine and Serum Biomarkers Indicative of Subclinical Kidney Damage in a Nephrotoxin Model

    Science.gov (United States)

    2009-05-01

    patients on chronic hemodialysis versus controls (Ziegelmeier et al., 2007). This study indicates that RBP4 levels correlate with c- reactive protein in...kidney injury, as well as cancer, rheumatoid arthritis , viral infections, and other chronic inflammatory diseases (Beorchia et al., 1981; Schuster...increase in plasma in dialysis patients , thought to be caused by an inflammatory response stimulated in the kidney due to interactions with hemodialysis

  2. Association of SNCA with Parkinson: replication in the Harvard NeuroDiscovery Center Biomarker Study

    Science.gov (United States)

    Ding, Hongliu; Sarokhan, Alison K.; Roderick, Sarah S.; Bakshi, Rachit; Maher, Nancy E.; Ashourian, Paymon; Kan, Caroline G.; Chang, Sunny; Santarlasci, Andrea; Swords, Kyleen E.; Ravina, Bernard M.; Hayes, Michael T.; Sohur, U. Shivraj; Wills, Anne-Marie; Flaherty, Alice W.; Unni, Vivek K.; Hung, Albert Y.; Selkoe, Dennis J.; Schwarzschild, Michael A.; Schlossmacher, Michael G.; Sudarsky, Lewis R.; Growdon, John H.; Ivinson, Adrian J.; Hyman, Bradley T.; Scherzer, Clemens R.

    2011-01-01

    Background Mutations in the α-synuclein gene (SNCA) cause autosomal dominant forms of Parkinson’s disease, but the substantial risk conferred by this locus to the common sporadic disease has only recently emerged from genome-wide association studies. Methods Here we genotyped a prioritized non-coding variant in SNCA intron-4 in 344 patients with Parkinson’s and 275 controls from the longitudinal Harvard NeuroDiscovery Center Biomarker Study. Results The common minor allele of rs2736990 was associated with elevated disease susceptibility (odds ratio = 1.40, P value = 0.0032). Conclusions This result increases confidence in the notion that in many clinically well-characterized patients genetic variation in SNCA contributes to “sporadic” disease. PMID:21953863

  3. Topic model-based mass spectrometric data analysis in cancer biomarker discovery studies.

    Science.gov (United States)

    Wang, Minkun; Tsai, Tsung-Heng; Di Poto, Cristina; Ferrarini, Alessia; Yu, Guoqiang; Ressom, Habtom W

    2016-08-18

    A fundamental challenge in quantitation of biomolecules for cancer biomarker discovery is owing to the heterogeneous nature of human biospecimens. Although this issue has been a subject of discussion in cancer genomic studies, it has not yet been rigorously investigated in mass spectrometry based proteomic and metabolomic studies. Purification of mass spectometric data is highly desired prior to subsequent analysis, e.g., quantitative comparison of the abundance of biomolecules in biological samples. We investigated topic models to computationally analyze mass spectrometric data considering both integrated peak intensities and scan-level features, i.e., extracted ion chromatograms (EICs). Probabilistic generative models enable flexible representation in data structure and infer sample-specific pure resources. Scan-level modeling helps alleviate information loss during data preprocessing. We evaluated the capability of the proposed models in capturing mixture proportions of contaminants and cancer profiles on LC-MS based serum proteomic and GC-MS based tissue metabolomic datasets acquired from patients with hepatocellular carcinoma (HCC) and liver cirrhosis as well as synthetic data we generated based on the serum proteomic data. The results we obtained by analysis of the synthetic data demonstrated that both intensity-level and scan-level purification models can accurately infer the mixture proportions and the underlying true cancerous sources with small average error ratios (data, we found more proteins and metabolites with significant changes between HCC cases and cirrhotic controls. Candidate biomarkers selected after purification yielded biologically meaningful pathway analysis results and improved disease discrimination power in terms of the area under ROC curve compared to the results found prior to purification. We investigated topic model-based inference methods to computationally address the heterogeneity issue in samples analyzed by LC/GC-MS. We observed

  4. Blood arsenic as a biomarker of arsenic exposure: Results from a prospective study

    International Nuclear Information System (INIS)

    Hall, Marni; Chen Yu; Ahsan, Habibul; Slavkovich, Vesna; Geen, Alexander van; Parvez, Faruque; Graziano, Joseph

    2006-01-01

    Exposure to arsenic (As)-contaminated drinking water affects millions of people worldwide. Arsenic exposure is associated with skin lesions, skin, lung, kidney and liver cancers, neurologic and cardiovascular effects. Past studies involving biomarkers of As exposure have typically examined urinary As (UAs) (adjusted for urinary creatinine), hair or toenail As, but not blood As (BAs) since blood concentrations are exceedingly low and are not detectable by conventional atomic absorption spectrophotometric techniques. In a case-cohort analysis of 303 newly diagnosed cases of skin lesions, and 849 subcohort members randomly selected from 8092 participants in the health effects of as longitudinal study (HEALS) in Araihazar, Bangladesh, we measured blood, urine and water As concentrations, and examined their associations with each other, and with the risk for skin lesions. BAs concentrations were highly correlated with creatinine-adjusted UAs concentrations (r = 0.85) and with water As (WAs) (r = 0.75). We observed consistent dose-response relationships between the risk of skin lesions and all the measures of As exposure. Rate ratios (RRs) for skin lesions by quintile of As exposure, adjusted for age and gender, revealed that the two highest quintiles were significantly related to an increased risk of skin lesions for each measure of exposure: BAs, UAs, WAs and a time-weighted water As variable. This prospective study confirms the increased risk of skin lesions in relation to As concentrations in blood, urine and water and also establishes that BAs is a useful biomarker of As exposure in this study population

  5. Storybook Read-Alouds to Enhance Students’ Comprehension Skills in ESL Classrooms: A Case Study

    Directory of Open Access Journals (Sweden)

    Ainon Omar

    2015-06-01

    Full Text Available The effectiveness of using storybooks during read-alouds to develop children’s comprehension skills as well as in understanding the story has been widely studied. The reading aloud strategy has also been proven through numerous researches to be the most highly recommended activity for encouraging language and literacy. The study identified the comprehension strategies used by the teachers during their read-aloud sessions, matched teachers’ current practices using the comprehension strategies to the identified practices for the approach, and obtained the teachers’ perceptions of their current practices of the comprehension strategies during reading aloud in their English language classrooms. The teachers’ comprehension strategies were matched with a research-based strategy for comprehending texts during read-alouds proposed by Whitehurst et al (1994. Three primary school English language teachers teaching in the rural schools participated in this study. Qualitative research methods were used in this study. Primary data was obtained through observations using an observation protocol; while secondary data was obtained through interviews from teachers. Findings from the study revealed that the three teachers employed a few of the comprehension strategies that were proposed by researchers in the field. The findings also indicate that the teachers utilized only the strategies that they thought were relevant to their teaching context and as such, proposed the need to provide teachers with knowledge on the best practices for conducting reading aloud to develop ESL students’ comprehension skills

  6. Atacama Rover Astrobiology Drilling Studies: Roving to Find Subsurface Preserved Biomarkers

    Science.gov (United States)

    Glass, B.; Davila, A.; Parro, V.; Quinn, R.; Willis, P.; Brinckerhoff, W.; DiRuggiero, J.; Williams, M.; Bergman, D.; Stoker, C.

    2016-05-01

    The ARADS project is a NASA PSTAR that will drill into a Mars analog site in search of biomarkers. Leading to a field test of an integrated rover-drill system with four prototype in-situ instruments for biomarker detection and analysis.

  7. Risk stratification after paracetamol overdose using mechanistic biomarkers: results from two prospective cohort studies.

    Science.gov (United States)

    Dear, James W; Clarke, Joanna I; Francis, Ben; Allen, Lowri; Wraight, Jonathan; Shen, Jasmine; Dargan, Paul I; Wood, David; Cooper, Jamie; Thomas, Simon H L; Jorgensen, Andrea L; Pirmohamed, Munir; Park, B Kevin; Antoine, Daniel J

    2018-02-01

    Paracetamol overdose is common but patient stratification is suboptimal. We investigated the usefulness of new biomarkers that have either enhanced liver specificity (microRNA-122 [miR-122]) or provide mechanistic insights (keratin-18 [K18], high mobility group box-1 [HMGB1], and glutamate dehydrogenase [GLDH]). The use of these biomarkers could help stratify patients for their risk of liver injury at hospital presentation. Using data from two prospective cohort studies, we assessed the potential for biomarkers to stratify patients who overdose with paracetamol. We completed two independent prospective studies: a derivation study (MAPP) in eight UK hospitals and a validation study (BIOPAR) in ten UK hospitals. Patients in both cohorts were adults (≥18 years in England, ≥16 years in Scotland), were diagnosed with paracetamol overdose, and gave written informed consent. Patients who needed intravenous acetylcysteine treatment for paracetamol overdose had circulating biomarkers measured at hospital presentation. The primary endpoint was acute liver injury indicating need for continued acetylcysteine treatment beyond the standard course (alanine aminotransferase [ALT] activity >100 U/L). Receiver operating characteristic (ROC) curves, category-free net reclassification index (cfNRI), and integrated discrimination index (IDI) were applied to assess endpoint prediction. Between June 2, 2010, and May 29, 2014, 1187 patients who required acetylcysteine treatment for paracetamol overdose were recruited (985 in the MAPP cohort; 202 in the BIOPAR cohort). In the derivation and validation cohorts, acute liver injury was predicted at hospital presentation by miR-122 (derivation cohort ROC-area under the curve [AUC] 0·97 [95% CI 0·95-0·98]), HMGB1 (0·95 [0·93-0·98]), and full-length K18 (0·95 [0·92-0·97]). Results were similar in the validation cohort (miR-122 AUC 0·97 [95% CI 0·95-0·99], HMGB1 0·98 [0·96-0·99], and full-length K18 0·93 [0·86-0·99]). A

  8. Novel biomarkers of mercury-induced autoimmune dysfunction: a Cross-sectional study in Amazonian Brazil

    Science.gov (United States)

    Motts, Jonathan A.; Shirley, Devon L.; Silbergeld, Ellen K.; Nyland, Jennifer F.

    2014-01-01

    Mercury is an ubiquitous environmental contaminant, causing both neurotoxicity and immunotoxicity. Given its ability to amalgamate gold, mercury is frequently used in small-scale artisanal gold mining. We have previously reported that elevated serum titers of antinuclear autoantibodies (ANA) are associated with mercury exposures of miners in gold mining. The goal of this project was to identify novel serum biomarkers of mercury-induced immunotoxicity and autoimmune dysregulation. We conducted an analysis of serum samples from a cross-sectional epidemiological study on miners working in Amazonian Brazil. In proteomic screening analyses, samples were stratified based on mercury concentrations and ANA titer and a subset of serum samples (N=12) were profiled using Immune Response Biomarker Profiling ProtoArray protein microarray for elevated autoantibodies. Of the up-regulated autoantibodies in the mercury-exposed cohort, potential target autoantibodies were selected based on relevance to pro-inflammatory and macrophage activation pathways. ELISAs were developed to test the entire sample cohort (N=371) for serum titers to the highest of these autoantibodies (anti-glutathione S-transferase alpha, GSTA1) identified in the high mercury/high ANA group. We found positive associations between elevated mercury exposure and up-regulated serum titers of 3760 autoantibodies as identified by ProtoArray. Autoantibodies identified as potential novel biomarkers of mercury-induced immunotoxicity include antibodies to the following proteins: GSTA1, tumor necrosis factor ligand superfamily member 13, linker for activation of T cells, signal peptide peptidase like 2B, stimulated by retinoic acid 13, and interferon induced transmembrane protein. ELISA analyses confirmed that mercury-exposed gold miners had significantly higher serum titers of anti-GSTA1 autoantibody [unadjusted odds ratio = 89.6; 95% confidence interval: 27.2, 294.6] compared to emerald miners (referent population

  9. Pooled results from 5 validation studies of dietary self-report instruments using recovery biomarkers for energy and protein intake

    Science.gov (United States)

    We pooled data from 5 large validation studies of dietary self-report instruments that used recovery biomarkers as references to clarify the measurement properties of food frequency questionnaires (FFQs) and 24-hour recalls. The studies were conducted in widely differing U.S. adult populations from...

  10. Identification of biomarkers for intake of protein from meat, dairy products and grains: A controlled dietary intervention study

    NARCIS (Netherlands)

    Altorf-van der Kuil, W.; Brink, E.J.; Boetje, M.; Siebelink, E.; Bijlsma, S.; Engberink, M.F.; Veer, P.V.'.; Tomé, D.; Bakker, S.J.L.; Baak, M.A. van; Geleijnse, J.M.

    2013-01-01

    In the present controlled, randomised, multiple cross-over dietary intervention study, we aimed to identify potential biomarkers for dietary protein from dairy products, meat and grain, which could be useful to estimate intake of these protein types in epidemiological studies. After 9 d run-in,

  11. Identification of biomarkers for intake of protein from meat, dairy products and grains : a controlled dietary intervention study

    NARCIS (Netherlands)

    Altorf-van der Kuil, Wieke; Brink, Elizabeth J.; Boetje, Martine; Siebelink, Els; Bijlsma, Sabina; Engberink, Marielle F.; van 't Veer, Pieter; Tome, Daniel; Bakker, Stephan J. L.; van Baak, Marleen A.; Geleijnse, Johanna M.

    2013-01-01

    In the present controlled, randomised, multiple cross-over dietary intervention study, we aimed to identify potential biomarkers for dietary protein from dairy products, meat and grain, which could be useful to estimate intake of these protein types in epidemiological studies. After 9 d run-in,

  12. [Tetra-saccharide glucose as a diagnostic biomarker for Pompe disease: a study with 35 patients].

    Science.gov (United States)

    Bobillo Lobato, Joaquín; Durán Parejo, Pilar; Tejero Díez, Pedro; Jiménez Jiménez, Luis M

    2013-08-04

    Pompe disease is a disorder originating from an acid alpha-glycosidase (AAG) enzyme deficiency. This disease produces an accumulation of lysosomal glycogen in different tissues, whereby the skeletal and heart muscles are especially involved. The established diagnosis is achieved through the identification of the AAG deficiency. There are also other secondary diagnostic biomarkers, such as tetra-saccharide glucose (Glc4), which shows high levels in the urine of these patients. In this study it is highlighted the usefulness of Glc4 as a diagnostic biomarker for Pompe disease in its different forms of presentation, using a high-performance liquid chromatography with ultraviolet detection (HPLC/UV) adapted to the study. A total of 75 individuals have been analyzed: 40 healthy controls and 35 patients diagnosed with Pompe disease. Twenty-four hour samples of urine were collected from all of the patients and their Glc4 levels were determined by means of HPLC/UV. The evaluation of the urinary Glc4 shows a high discrimination ability between healthy/sick individuals. In addition, the results obtained have allowed to establish the most appropriate level of decision or cut-off point for the identification of sick people. Glc4 urinary levels are found to be high in patients suffering from Pompe disease and even though increased levels are also found in other conditions, the existence of a AAG deficiency together with a compatible clinical symptoms, prove very helpful for a correct diagnosis of this serious disease. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  13. Flow Injection/Sequential Injection Analysis Systems: Potential Use as Tools for Rapid Liver Diseases Biomarker Study

    Directory of Open Access Journals (Sweden)

    Supaporn Kradtap Hartwell

    2012-01-01

    Full Text Available Flow injection/sequential injection analysis (FIA/SIA systems are suitable for carrying out automatic wet chemical/biochemical reactions with reduced volume and time consumption. Various parts of the system such as pump, valve, and reactor may be built or adapted from available materials. Therefore the systems can be at lower cost as compared to other instrumentation-based analysis systems. Their applications for determination of biomarkers for liver diseases have been demonstrated in various formats of operation but only a few and limited types of biomarkers have been used as model analytes. This paper summarizes these applications for different types of reactions as a guide for using flow-based systems in more biomarker and/or multibiomarker studies.

  14. A Study of Holistic and Subskill Instructional Approaches to Reading Comprehension.

    Science.gov (United States)

    Vacca, Richard T.

    1980-01-01

    In a six-week study involving seventh- to ninth-grade students in a summer corrective reading program, neither the holistic nor the subskill treatment had a significant advantage in improving student reading comprehension or attitude toward reading. (JT)

  15. Diagnostic and economic evaluation of new biomarkers for Alzheimer’s disease: the research protocol of a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Handels Ron LH

    2012-08-01

    Full Text Available Abstract Background New research criteria for the diagnosis of Alzheimer’s disease (AD have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1 assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2 perform a cost-consequence analysis and 3 assess long-term cost-effectiveness by an economic model. Methods/design In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers. The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results

  16. A comparative study of biological and metabolic biomarkers between healthy individuals and patients with acne vulgaris: A cross-sectional study protocol.

    Science.gov (United States)

    Kim, Kyuseok; Ha, Injin; Kim, Eunok; Kim, Kyunglee

    2017-11-01

    Acne is a multifactorial dermatosis, which is influenced not only by hormones but also by the biochemical relationship between them and the pilosebaceous unit. Inflammatory cytokines, chemokines, active oxygen, and zinc are known to be associated with the development of acne. Further, steroid metabolism is known as one of the important factors related to sebum secretion and comedone formation in acne. However, there is a lack of studies comparing these human biomarkers between healthy individuals and patients with acne. In particular, no study has investigated the relationship between human biomarkers and patterns of acne yet.The purpose of this study is to investigate diagnostic human biomarkers in acne by comparing the biological and metabolic biomarkers between healthy individuals and patients with acne and identify the relationship between human biomarkers and patterns of acne.This study is a protocol for a cross-sectional study. Forty healthy participants and 60 patients with acne will be recruited at 1 center. We will collect their blood samples and analyze the molecular biological and metabolic biomarkers (cytokines, chemokines, reactive oxygen species, corticotropin-releasing hormone, zinc, amino acid, 1-carbon metabolite, lipid metabolite, etc.). Further, we will administer questionnaires regarding their diet, sleep, stress, and other factors relating to acne and measure their skin elasticity.The study protocol was approved by the Institutional Review Board of Oriental Medical Hospital at Kyung Hee Medical Center (KOMCIRB-161118-HR-062). Written informed consent will be obtained from all the participants. The trial was registered in the Clinical Research Information Service, Republic of Korea: KCT0002212.This trial will provide evidence regarding diagnostic human biomarkers in acne and the relationship between the human biomarkers and patterns of acne.

  17. Biomarkers in Autism

    Directory of Open Access Journals (Sweden)

    Robert eHendren

    2014-08-01

    Full Text Available Autism spectrum disorders (ASD are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

  18. A Study on Strategies for Teaching Speaking and Reading Comprehension Skills

    OpenAIRE

    AHMAD; Prof. Dr.I Ketut Seken,MA; Dra. Luh Putu Artini, MA., Ph.D

    2013-01-01

    The central intention of this study was to analyze the English teachers’ strategies in teaching speaking and reading comprehension skills in SMPN 1 Selong. It was conducted to get detailed information about the students’ responses toward their teachers’ strategies in teaching speaking and reading comprehension skills. This study employed a qualitative research design. Necessary data were gathered using open-ended question, classroom observation, interview, and questionnaire. The result ...

  19. Aspects of open-flavour mesons in a comprehensive DSBSE study

    Energy Technology Data Exchange (ETDEWEB)

    Hilger, T. [University of Graz, NAWI Graz, Institute of Physics, Graz (Austria); Austrian Academy of Sciences, Institute of High Energy Physics, Vienna (Austria); Gomez-Rocha, M. [ECT*, Villazzano (Trento) (Italy); Krassnigg, A. [University of Graz, NAWI Graz, Institute of Physics, Graz (Austria); Lucha, W. [Austrian Academy of Sciences, Institute of High Energy Physics, Vienna (Austria)

    2017-10-15

    Open-flavour meson studies are the necessary completion to any comprehensive investigation of quarkonia. We extend recent studies of quarkonia in the Dyson-Schwinger-Bethe-Salpeter equation approach to explore their results for all possible flavour combinations. Within the inherent limitations of the setup, we present the most comprehensive results for meson masses and leptonic decay constants currently available and put them in perspective with respect to experiment and other approaches. (orig.)

  20. Theory of mind in emerging reading comprehension: A longitudinal study of early indirect and direct effects.

    Science.gov (United States)

    Atkinson, Lynette; Slade, Lance; Powell, Daisy; Levy, Joseph P

    2017-12-01

    The relation between children's theory of mind (ToM) and emerging reading comprehension was investigated in a longitudinal study over 2.5years. A total of 80 children were tested for ToM, decoding, language skills, and executive function (EF) at Time 1 (mean age=3;10 [years;months]). At Time 2 (mean age=6;03), children's word reading efficiency, language skills, and reading comprehension were measured. Mediation analysis showed that ToM at Time 1, when children were around 4years old, indirectly predicted Time 2 reading comprehension, when children were 6years old, via language ability after controlling for age, nonverbal ability, decoding, EF, and earlier language ability. Importantly, ToM at 4years also directly predicted reading comprehension 2.5years later at 6years. This is the first longitudinal study to show a direct contribution of ToM to reading comprehension in typical development. Findings are discussed in terms of the simple view of reading (SVR); ToM not only supports reading comprehension indirectly by facilitating language but also contributes to it directly over and above the SVR. The potential role of metacognition is considered when accounting for the direct contribution of early ToM to later reading comprehension. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Screening for biomarkers of liver injury induced by Polygonum multiflorum: a targeted metabolomic study

    Directory of Open Access Journals (Sweden)

    Qin eDong

    2015-10-01

    Full Text Available Heshouwu (HSW, the dry roots of Polygonum multiflorum, a classical traditional Chinese medicine is used as a tonic for a wide range of conditions,particularly those associated with aging. However, it tends to be taken overdose or long term in these years, which has resulted in liver damage reported in many countries. In this study, the indicative roles of nine bile acids (BAs were evaluated to offer potential biomarkers for HSW induced liver injury. Nine BAs including cholic acid (CA and chenodeoxycholic acid (CDCA, taurocholic acid (TCA, glycocholic acid (GCA, glycochenodeoxycholic acid (GCDCA, deoxycholic acid (DCA, glycodeoxycholic acid (GDCA, ursodeoxycholic acid (UDCA and hyodeoxycholic acid (HDCA in rat bile and serum were detected by a developed LC-MS method after 42 days treatment. Partial least square-discriminate analysis (PLS-DA was applied to evaluate the indicative roles of the nine BAs, and metabolism of the nine BAs was summarized. Significant change was observed for the concentrations of nine BAs in treatment groups compared with normal control; In the PLS-DA plots of nine BAs in bile, normal control and raw HSW groups were separately clustered and could be clearly distinguished, GDCA was selected as the distinguished components for raw HSW overdose treatment group. In the PLS-DA plots of nine BAs in serum, the normal control and raw HSW overdose treatment group were separately clustered and could be clearly distinguished, and HDCA was selected as the distinguished components for raw HSW overdose treatment group. The results indicated the perturbation of nine BAs was associated with HSW induced liver injury; GDCA in bile, as well as HDCA in serum could be selected as potential biomarkers for HSW induced liver injury; it also laid the foundation for the further search on the mechanisms of liver injury induced by HSW .

  2. Short-Term Exposure to Air Pollution and Biomarkers of Oxidative Stress: The Framingham Heart Study.

    Science.gov (United States)

    Li, Wenyuan; Wilker, Elissa H; Dorans, Kirsten S; Rice, Mary B; Schwartz, Joel; Coull, Brent A; Koutrakis, Petros; Gold, Diane R; Keaney, John F; Lin, Honghuang; Vasan, Ramachandran S; Benjamin, Emelia J; Mittleman, Murray A

    2016-04-28

    Short-term exposure to elevated air pollution has been associated with higher risk of acute cardiovascular diseases, with systemic oxidative stress induced by air pollution hypothesized as an important underlying mechanism. However, few community-based studies have assessed this association. Two thousand thirty-five Framingham Offspring Cohort participants living within 50 km of the Harvard Boston Supersite who were not current smokers were included. We assessed circulating biomarkers of oxidative stress including blood myeloperoxidase at the seventh examination (1998-2001) and urinary creatinine-indexed 8-epi-prostaglandin F2α (8-epi-PGF2α) at the seventh and eighth (2005-2008) examinations. We measured fine particulate matter (PM2.5), black carbon, sulfate, nitrogen oxides, and ozone at the Supersite and calculated 1-, 2-, 3-, 5-, and 7-day moving averages of each pollutant. Measured myeloperoxidase and 8-epi-PGF2α were loge transformed. We used linear regression models and linear mixed-effects models with random intercepts for myeloperoxidase and indexed 8-epi-PGF2α, respectively. Models were adjusted for demographic variables, individual- and area-level measures of socioeconomic position, clinical and lifestyle factors, weather, and temporal trend. We found positive associations of PM2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2- to 7-day moving averages of PM2.5 and sulfate were consistently positively associated with 8-epi-PGF2α. Stronger positive associations of black carbon and sulfate with myeloperoxidase were observed among participants with diabetes than in those without. Our community-based investigation supports an association of select markers of ambient air pollution with circulating biomarkers of oxidative stress. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  3. Novel Stool-Based Protein Biomarkers for Improved Colorectal Cancer Screening: A Case-Control Study.

    Science.gov (United States)

    Bosch, Linda J W; de Wit, Meike; Pham, Thang V; Coupé, Veerle M H; Hiemstra, Annemieke C; Piersma, Sander R; Oudgenoeg, Gideon; Scheffer, George L; Mongera, Sandra; Sive Droste, Jochim Terhaar; Oort, Frank A; van Turenhout, Sietze T; Larbi, Ilhame Ben; Louwagie, Joost; van Criekinge, Wim; van der Hulst, Rene W M; Mulder, Chris J J; Carvalho, Beatriz; Fijneman, Remond J A; Jimenez, Connie R; Meijer, Gerrit A

    2017-12-19

    The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement. To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas. Case-control study. Colonoscopy-controlled referral population from several centers. 315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples). Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples. In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P control samples (P control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening. Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU

  4. A brief review and evaluation of earthworm biomarkers in soil pollution assessment.

    Science.gov (United States)

    Shi, Zhiming; Tang, Zhiwen; Wang, Congying

    2017-05-01

    Earthworm biomarker response to pollutants has been widely investigated in the assessment of soil pollution. However, whether and how the earthworm biomarker-approach can be actually applied to soil pollution assessment is still a controversial issue. This review is concerned about the following points: 1. Despite much debate, biomarker is valuable to ecotoxicology and biomarker approach has been properly used in different fields. Earthworm biomarker might be used in different scenarios such as large-scale soil pollution survey and soil pollution risk assessment. Compared with physicochemical analysis, they can provide more comprehensive and straightforward information about soil pollution at low cost. 2. Although many earthworm species from different ecological categories have been tested, Eisenia fetida/andrei is commonly used. Many earthworm biomarkers have been screened from the molecular to the individual level, while only a few biomarkers, such as avoidance behavior and lysosomal membrane stability, have been focused on. Other aspects of the experimental design were critically reviewed. 3. More studies should focus on determining the reliability of various earthworm biomarkers in soil pollution assessment in future research. Besides, establishing a database of a basal level of each biomarker, exploring biomarker response in different region/section/part of earthworm, and other issues are also proposed. 4. A set of research guideline for earthworm biomarker studies was recommended, and the suitability of several earthworm biomarkers was briefly evaluated with respect to their application in soil pollution assessment. This review will help to promote further studies and practical application of earthworm biomarker in soil pollution assessment.

  5. Terrestrial ecology. Comprehensive study of the grassland biome

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Terrestrial ecology and grassland biome studies are designed to characterize the biota of the Hanford Reservation, elucidate seasonal dynamics of plant productivity, decomposition and mineral behavior patterns of important plant communities, and, to study the response of these communities to important natural environmental stresses, such as weather, wildfire and man-induced alterations of communities (influenced by grazing cattle and severe mechanical disturbance of the soil, such as affected by plowing or burial of waste materials or construction activities). A detailed account of the important findings of a 5-yr study is currently being prepared by the terrestrial ecology section staff for publication as a contribution to the International Biological Program Grassland Biome project

  6. A COMPREHENSIVE STUDY OF DEPRESSION IN ADOLESCENT GIRLS

    Directory of Open Access Journals (Sweden)

    Preeti

    2015-06-01

    Full Text Available Depressive disorders in adolescents are a major cause of concern. As these disorders are subject to high recurrences in adulthood. The risk factors have to be identified and prompt treatment should be initiated. 15% have depression and 56% have depressive symptoms. The causes ranged from financ ial, broken homes, or death in the family, chronic illness. Symptoms of depression were unhappiness, restlessness, agitation, anger, dis interest in a pleasurable job. In the schools failure, in academics, in 47% girls lead to depression, partiality, abuse , was also contributing factors. Several studies, in particular, a study from Delhi showed depression to be the 3rd leading cause of death. Our study showed 6% , 12% had problems at home, 73% had clear idea about future plans. The problem should be identified and a team of psychiatrics, psychologists, pediatrician should bring down the problem.

  7. A comprehensive family-based replication study of schizophrenia genes

    DEFF Research Database (Denmark)

    Aberg, Karolina A; Liu, Youfang; Bukszár, Jozsef

    2013-01-01

     768 control subjects from 6 databases and, after quality control 6298 individuals (including 3286 cases) from 1811 nuclear families. MAIN OUTCOMES AND MEASURES Case-control status for SCZ. RESULTS Replication results showed a highly significant enrichment of SNPs with small P values. Of the SNPs...... in an independent family-based replication study that, after quality control, consisted of 8107 SNPs. SETTING Linkage meta-analysis, brain transcriptome meta-analysis, candidate gene database, OMIM, relevant mouse studies, and expression quantitative trait locus databases. PATIENTS We included 11 185 cases and 10...

  8. Contribution to comprehensive study of aluminium alloy Aa 5083 ...

    African Journals Online (AJOL)

    PROMOTING ACCESS TO AFRICAN RESEARCH ... Corrosion induced by elemental mercury in aqueous media of industrial Aluminium alloys AA5083 used in heat exchanger industries of natural gas liquefaction has been studied by linear sweep voltammétry on ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  9. Developing a Comprehensive Housing Strategy: A Case Study

    Science.gov (United States)

    Marsters, Tim; Bliss, Kelly

    2007-01-01

    In the current highly competitive higher education market in North America, many colleges have identified the importance of upgrading their existing residential housing facilities as part of their strategy to attract and retain students. The case study discussed in this article describes the successful planning process used by Perkins+Will and…

  10. Reading Comprehension and Translation Performance of English Linguistics Students of Hung Vuong University: A Correlational Study

    Directory of Open Access Journals (Sweden)

    Cuc Thi Kim Pham

    2017-09-01

    Full Text Available The study aimed to correlate the reading comprehension and translation performance of English linguistic students, then inform some pedagogical implications for the teaching of reading comprehension in translation classes in order to enhance the translation quality performed by the students. To this end, 45 junior students of English linguistics specialization of Hung Vuong University, including 5 males and 40 females, aged from 20 to 22, were subject to a TOEFL reading comprehension test and a translation performance test (ATA guidelines, 2011. Data were analyzed using the Pearson Correlation, SPSS version 20.0. The coefficient correlation of students’ reading comprehension and their translation performance was noted 0.721 at the significant level of 0.01. It was found that the Reading comprehension was closely related to translation performance. Along the reading comprehension question types, translation performance was affected by the ability to determine gist and main ideas of the text, identify the vocabulary, infer the implied meanings and identify the writer’s style and attitudes. The results were discussed, and implications for teaching reading comprehension to enhance translation performance were presented.

  11. Integration of ¹H NMR and UPLC-Q-TOF/MS for a comprehensive urinary metabonomics study on a rat model of depression induced by chronic unpredictable mild stress.

    Directory of Open Access Journals (Sweden)

    Hong-Mei Jia

    Full Text Available Depression is a type of complex psychiatric disorder with long-term, recurrent bouts, and its etiology remains largely unknown. Here, an integrated approach utilizing (1H NMR and UPLC-Q-TOF/MS together was firstly used for a comprehensive urinary metabonomics study on chronic unpredictable mild stress (CUMS treated rats. More than twenty-nine metabolic pathways were disturbed after CUMS treatment and thirty-six potential biomarkers were identified by using two complementary analytical technologies. Among the identified biomarkers, nineteen (10, 11, 16, 17, 21-25, and 27-36 were firstly reported as potential biomarkers of CUMS-induced depression. Obviously, this paper presented a comprehensive map of the metabolic pathways perturbed by CUMS and expanded on the multitude of potential biomarkers that have been previously reported in the CUMS model. Four metabolic pathways, including valine, leucine and isoleucine biosynthesis; phenylalanine, tyrosine and tryptophan biosynthesis; tryptophan metabolism; synthesis and degradation of ketone bodies had the deepest influence in the pathophysiologic process of depression. Fifteen potential biomarkers (1-2, 4-6, 15, 18, 20-23, 27, 32, 35-36 involved in the above four metabolic pathways might become the screening criteria in clinical diagnosis and predict the development of depression. Moreover, the results of Western blot analysis of aromatic L-amino acid decarboxylase (DDC and indoleamine 2, 3-dioxygenase (IDO in the hippocampus of CUMS-treated rats indicated that depletion of 5-HT and tryptophan, production of 5-MT and altered expression of DDC and IDO together played a key role in the initiation and progression of depression. In addition, none of the potential biomarkers were detected by NMR and LC-MS simultaneously which indicated the complementary of the two kinds of detection technologies. Therefore, the integration of (1H NMR and UPLC-Q-TOF/MS in metabonomics study provided an approach to identify

  12. Prediction of fruit and vegetable intake from biomarkers using individual participant data of diet-controlled intervention studies

    NARCIS (Netherlands)

    Souverein, O.W.; Vries, J.H.M. de; Freese, R.; Watzl, B.; Bub, A.; Miller, E.R., III; Castenmiller, J.J.M.; Pasman, W.J.; Hof, K. van het; Chopra, M.; Karlsen, A.; Dragsted, L.O.; Winkels, R.; Itsiopoulos, C.; Brazionis, L.; O'Dea, K.; Loo-Bouwman, C.A. van; Naber, T.H.J.; Voet, H. van der; Boshuizen, H.C.

    2015-01-01

    Fruit and vegetable consumption produces changes in several biomarkers in blood. The present study aimed to examine the dose-response curve between fruit and vegetable consumption and carotenoid (α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C

  13. Prediction of fruit and vegetable intake from biomarkers using individual participant data of diet-controlled intervention studies

    DEFF Research Database (Denmark)

    Souverein, Olga W; de Vries, Jeanne H M; Freese, Riitta

    2015-01-01

    concentrations. Furthermore, a prediction model of fruit and vegetable intake based on these biomarkers and subject characteristics (i.e. age, sex, BMI and smoking status) was established. Data from twelve diet-controlled intervention studies were obtained to develop a prediction model for fruit and vegetable...

  14. Evaluation of C-reactive protein as an inflammatory biomarker in rabbits for vaccine nonclinical safety studies

    NARCIS (Netherlands)

    Destexhe, E.; Prinsen, M.K.; Schöll, I. van; Kuper, C.F.; Garçon, N.; Veenstra, S.; Segal, L.

    2013-01-01

    Introduction: Inflammatory reactions are one of the potential safety concerns that are evaluated in the framework of vaccine safety testing. In nonclinical studies, the assessment of the inflammation relies notably on the measurement of biomarkers. C-reactive protein (CRP) is an acute-phase plasma

  15. Pooled results from five validation studies of dietary self-report instruments using recovery biomarkers for potassium and sodium intake

    Science.gov (United States)

    We have pooled data from five large validation studies of dietary self-report instruments that used recovery biomarkers as referents to assess food frequency questionnaires (FFQs) and 24-hour recalls. We reported on total potassium and sodium intakes, their densities, and their ratio. Results were...

  16. Biomarkers kinetics in the assessment of ventilator-associated pneumonia response to antibiotics - results from the BioVAP study

    NARCIS (Netherlands)

    Póvoa, Pedro; Martin-Loeches, Ignacio; Ramirez, Paula; Bos, Lieuwe D.; Esperatti, Mariano; Silvestre, Joana; Gili, Gisela; Goma, Gemma; Berlanga, Eugenio; Espasa, Mateu; Gonçalves, Elsa; Torres, Antoni; Artigas, Antonio

    2017-01-01

    Purpose: Our aim was to evaluate the role of biomarker kinetics in the assessment of ventilator-associated pneumonia (VAP) response to antibiotics. Materials and methods: We performed a prospective, multicenter, observational study to evaluate in 37 microbiologically documented VAP, the kinetics of

  17. Correlation of serum MMP3 and other biomarkers with clinical outcomes in patients with ankylosing spondylitis: A pilot study

    Science.gov (United States)

    The studies aimed to assess a set of biomarkers for their correlations with disease activity/severity of patients with ankylosing spondylitis (AS). A total of 24 AS patients were treated with etanercept and prospectively followed for 12 weeks. Serum levels of TNF-alpha, IFN-gamma, TGF-beta, IL6, IL1...

  18. Biomarkers of Dairy Fatty Acids and Risk of Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis

    NARCIS (Netherlands)

    Oliveira Otto, de M.C.; Nettleton, J.A.; Lemaitre, R.N.; Steffen, L.M.; Kromhout, D.; Rich, R.L.; Tsai, M.Y.; Jacobs, D.R.; Mozaffarian, D.

    2013-01-01

    Background Evidence regarding the role of dairy fat intake in cardiovascular disease (CVD) has been mixed and inconclusive. Most earlier studies have used self-reported measures of dietary intake and focused on relatively racially homogeneous populations. Circulating biomarkers of dairy fat in a

  19. Comprehensive Study of Acute Effects and Recovery After Concussion

    Science.gov (United States)

    2015-10-01

    MCW IRB regarding personality questionnaire changes and head impact sensor company changes • Amendment under review as of Sept 29, 2015 regarding...a large (3Tb) memory system, and four general purpose graphical processing unit (GPU) systems, each with four Nvidia K40 GPUs. Each of these... company changed prior to study implementation and MCW IRB provided oversight for Banyan Biomarkers’ research activities. Approved by MCW IRB Aug 24

  20. Comprehensive Study of Plasma-Wall Sheath Transport Phenomena

    Science.gov (United States)

    2016-10-26

    the floating potential of wall material samples immersed in a low-temperature plasma were studied. Hysteresis is found to be due to secondary electron...continued research into plasma sheath physics. Hysteresis effects observed in the floating potential of wall material samples immersed in a low... Journal of Applied Physics, Volume 119, March 2016, pp. 113305 1-5. DISTRIBUTION A: Distribution approved for public release. 8 Figure 2

  1. Comprehensive studies on regulatory issues of spent fuel pools

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-08-15

    An existence of safety issues in the spent fuel pool (SFP) was recognized by the nuclear accident at the Fukushima Daiichi Nuclear Power Station, and many reports on the accident describe needs of countermeasures for SFP under sever accidents. For research planning, thermal hydraulic behaviors of SFP and possibility of occurrence of re-criticality conditions in SFP were studied by computational approaches. In the studies on thermal hydraulic behaviors, possibilities of adiabatic conditions in a spent fuel bundle were identified because natural circulation cooling of air could be terminated due to flow path blockage by pool water and steam cooling could be terminated due to reduction of pool water evaporation originated from cold water injection by emergency water supply. In the re-criticality study, in the case of the un-borated lack, it was shown that the neutron multiplication factor became larger than unity when the difference of water levels inside and outside the channel box larger than some values. (author)

  2. The Videofluorographic Swallowing Study in Rheumatologic Diseases: A Comprehensive Review

    Science.gov (United States)

    Di Piazza, Ambra; Costanzo, Massimo; Scopelliti, Laura; Salvaggi, Francesco; Cupido, Francesco; Salerno, Sergio; Lo Casto, Antonio; Midiri, Massimo; Lo Re, Giuseppe; Lagalla, Roberto

    2017-01-01

    Autoimmune connective tissue diseases are a heterogeneous group of pathologies that affect about 10% of world population with chronic evolution in 20%–80%. Inflammation in autoimmune diseases may lead to serious damage to other organs including the gastrointestinal tract. Gastrointestinal tract involvement in these patients may also due to both a direct action of antibodies against organs and pharmacological therapies. Dysphagia is one of the most important symptom, and it is caused by failure of the swallowing function and may lead to aspiration pneumonia, malnutrition, dehydration, weight loss, and airway obstruction. The videofluorographic swallowing study is a key diagnostic tool in the detection of swallowing disorders, allowing to make an early diagnosis and to reduce the risk of gastrointestinal and pulmonary complications. This technique helps to identify both functional and structural anomalies of the anatomic chain involved in swallowing function. The aim of this review is to systematically analyze the basis of the pathological involvement of the swallowing function for each rheumatological disease and to show the main features of the videofluorographic study that may be encountered in these patients. PMID:28706536

  3. A comprehensive review of metal-induced cellular transformation studies.

    Science.gov (United States)

    Chen, Qiao Yi; Costa, Max

    2017-09-15

    In vitro transformation assays not only serve practical purposes in screening for potential carcinogenic substances in food, drug, and cosmetic industries, but more importantly, they provide a means of understanding the critical biological processes behind in vivo cancer development. In resemblance to cancer cells in vivo, successfully transformed cells display loss of contact inhibition, gain of anchorage independent growth, resistant to proper cell cycle regulation such as apoptosis, faster proliferation rate, potential for cellular invasion, and ability to form tumors in experimental animals. Cells purposely transformed using metal exposures enable researchers to examine molecular changes, dissect various stages of tumor formation, and ultimately elucidate metal induced cancer mode of action. For practical purposes, this review specifically focuses on studies incorporating As-, Cd-, Cr-, and Ni-induced cell transformation. Through investigating and comparing an extensive list of studies using various methods of metal-induced transformation, this review serves to bridge an information gap and provide a guide for avoiding procedural discrepancies as well as maximizing experimental efficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. The Effect of Question Position on Listening Comprehension: A Case Study

    OpenAIRE

    Naci Yildiz; Nikoloz Parjanadze; Mustafa Albay

    2015-01-01

    Though speaking has been considered as the most important skill in foreign language learning process, listening has a fundamental value because learning does not occur without comprehensible input. Listening is a complex process in which learners must do analysis to accurately interpret. In listening learners need to interpret with a speaker to construct meaning. This study tries to find out whether listening strategies are effective to influence listening comprehension and the major goal of ...

  5. CD64 on monocytes and granulocytes in severe acute bronchiolitis: Pilot study on its usefulness as a bacterial infection biomarker.

    Science.gov (United States)

    García-Salido, Alberto; Serrano-González, Ana; Casado-Flores, Juan; Sierra-Colomina, Montserrat; de Azagra-Garde, Amelia Martínez; García-Teresa, María Ángeles; Melen, Gustavo J; Ramírez-Orellana, Manuel

    2018-02-27

    The CD64 receptor has been described as a biomarker of bacterial infection. We speculated that CD64 surface expression on monocytes and granulocytes of children with severe acute bronchiolitis (SAB) could be altered in cases of probable bacterial infection (PBI) determined using classical biomarkers (procalcitonin and C-reactive protein, leukocyte count, and radiographic findings). A prospective observational pilot study was conducted from October 2015 to February 2016 in children admitted for pediatric critical care. A blood sample was taken in the first 24 hours of admission, and CD64 was measured by flow cytometry. The values obtained were analyzed and correlated with traditional biomarkers of PBI. Thirty-two children were included; a correlation was found between CD64 expression and the PBI criteria. CD64 surface expression was higher in children with PBI (area under the receiver operating characteristic curve of 0.73; P = 0.042) and the percentage of CD64 + granulocytes was higher in children with PBI. This is the first study to describe CD64 surface expression on monocytes and granulocytes in SAB, finding CD64 values to be higher in children with PBI. Larger clinical studies are needed to elucidate the real accuracy of CD64 as a biomarker of bacterial infection. ©2018 Society for Leukocyte Biology.

  6. Can we better predict the biologic behavior of incidental IPMN? A comprehensive analysis of molecular diagnostics and biomarkers in intraductal papillary mucinous neoplasms of the pancreas.

    Science.gov (United States)

    Tulla, Kiara A; Maker, Ajay V

    2018-03-01

    Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging characteristics to determine appropriate surgical candidates. However, the majority of resected cysts remain low-risk lesions, many of which may be feasible to have under surveillance. We herein characterize the most promising and up-to-date molecular diagnostics in order to identify optimal components of a molecular signature to distinguish levels of IPMN dysplasia. A comprehensive systematic review of pertinent literature, including our own experience, was conducted based on the PRISMA guidelines. Molecular diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and serum were evaluated and organized into the following categories: oncogenes, tumor suppressor genes, glycoproteins, markers of the immune response, proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific targets in each of these categories, and in aggregate, were identified by their ability to both characterize a cyst as an IPMN and determine the level of cyst dysplasia. Combining molecular signatures with clinical and imaging features in this era of next-generation sequencing and advanced computational analysis will enable enhanced sensitivity and specificity of current models to predict the biologic behavior of IPMN.

  7. 1,2-Propanediol. Comprehensive experimental and theoretical study

    International Nuclear Information System (INIS)

    Verevkin, Sergey P.; Emel'yanenko, Vladimir N.; Nell, Gernot

    2009-01-01

    The standard (p 0 =0.1MPa) molar enthalpy of formation at the temperature 298.15 K of the liquid 1,2-propanediol was measured using combustion calorimetry. Molar enthalpies of vaporization of isomeric 1,2-propanediols were obtained from the temperature dependence of the vapor pressure measured by the transpiration method. Thermochemical investigations of 1,2-ethanediol and 1,2-propanediol available in the literature were collected and combined with own experimental results. This collection together with the new experimental results reported here has helped to resolve contradictions in the available sublimation enthalpies data and to recommend consistent and reliable set of vaporization and formation enthalpies for both diols under study. Ab initio calculations of gaseous molar enthalpy of formation of 1,2-ethanediol and 1,2-propanediol have been performed using the G3MP2 method and results are in excellent agreement with the selected experimental data.

  8. A comprehensive review of oil spill combustion studies

    International Nuclear Information System (INIS)

    Walavalkar, A.Y.; Kulkarni, A.K.

    1996-01-01

    The complex process of in-situ burning of oil or a water-in-oil emulsion floating on top of a water-base, such as the ocean, was discussed. The process was examined before, during and after actual combustion. In general, the success of oil spill combustion is measured in terms of the fraction of the spilled oil or emulsion that is burned away. However, the air and aquatic pollution caused by the combustion should also be considered. The physical conditions such as wind velocity, waves and the presence or absence of a containment device, such as a fire boom, could determine the continuation of the combustion process. An overview of the oil spill combustion techniques was provided. There still remains a need for fundamental studies, especially in mathematical modeling, to understand the basic mechanisms and predict the applicability of the in-situ combustion. 74 refs., 7 tabs., 3 figs

  9. Wuskwatim generation project : Canadian Environmental Assessment Act comprehensive study report

    International Nuclear Information System (INIS)

    2005-10-01

    This study report described the plan by Manitoba Hydro and the Nisichawayasihk Cree Nation (NCN) to construct a new 200- megawatt (MW) generating station at Taskinigup Falls on the Burntwood River, near the outlet of Wuskwatim Lake. This hydroelectric power project will allow Manitoba Hydro to meet its projected energy needs within the next two decades as identified in its 2002/03 Power Resource Plan. It will also allow Manitoba Hydro and NCN to obtain additional export revenues and profits by advancing the in-service date of the Project from 2020 to 2009. A formal environmental assessment is required under the Canadian Environmental Assessment Act (CEAA) because Fisheries and Oceans Canada (DFO) has determined that the Project would cause fish habitat losses requiring an authorization under the Fisheries Act. Many of the structures to be built in navigable waters would also require formal approval under the Navigable Waters Protection Act (NWPA), which has prompted this application of the CEAA. This environmental assessment report has been prepared by DFO in consultation with Transport Canada and other federal authorities concerned. It provides a summary of the Wuskwatim Generation Project and the environment in which it will be built and operated. In addition, the results of public consultations are discussed. It presents an assessment of the Project's influence on fish and fish habitat, birds, species at risk, human health (local air quality, quality of drinking water and consumption of fishery products), navigation, use of renewable resources, and current use of lands and resources for traditional purposes by Aboriginal persons (hunting, trapping, gathering, subsistence fishing and heritage sites). It was concluded that the proposed Project, as defined by the scope of the study, is not likely to cause significant adverse environmental effects. 45 refs., 5 tabs., 13 figs., 3 appendices

  10. Comprehensive study of psi meson production. Progress report

    International Nuclear Information System (INIS)

    Jones, S.T.; Harms, B.C.

    1985-01-01

    Our first paper under this grant is a calculation of prompt lepton production in upsilon and toponium decay. The results should prove useful in identifying signals for charm or bottom production. Our work has led to some improvement in our understanding of psi production in hadronic interactions, although further work is needed. Attempts to explain the difference between experimental and theoretical rates of psi hadroproduction led to a study of quark-gluon scattering, which proved to have a negative impact on the theoretical cross section once a leading mass singularity was absorbed into the gluon distribution function. Our study of psi production in B meson decays has led to an improvement in the leading-log calculation of this rate, which gives a much more precise prediction of the decay rate. We have also calculated all first-order QCD corrections to this weak process. We are now completing a companion calculation of n/sub c/ production, for which there is presently no data. Dr. Harms and Dr. Cox have collaborated on an attempt to determine the dominant contribution to the difference sigma(pN → psi x) - sigma(anti pN → psi x). The lowest order process contributing to this difference (q anti q → psi GG) has been shown previously to be small. They have calculated the next order process (q anti q → G*G* → psi G) and have apparently uncovered a new example of the violation of the Bloch-Nordsieck mechanism in QCD. Our work outside the realm of QCD has included a new fit to the total pp and anti pp cross sections. Dr. Cox has also been pursuing the question of representations of extended (especially N=8) supersymmetry

  11. Validation of biomarkers for the study of environmental carcinogens: a review

    DEFF Research Database (Denmark)

    Gallo, Valentina; Khan, Aneire; Gonzales, Carlos

    2008-01-01

    There is a need for validation of biomarkers. Our aim is to review published work on the validation of selected biomarkers: bulky DNA adducts, N-nitroso compounds, 1-hydroxypyrene, and oxidative damage to DNA. A systematic literature search in PubMed was performed. Information on the variability...... and reliability of the laboratory tests used for biomarkers measurements was collected. For the evaluation of the evidence on validation we referred to the ACCE criteria. Little is known about intraindividual variation of DNA adduct measurements, but measurements have a good repeatability irrespective...... of the technique used for their identification; reproducibility improved after the correction for a laboratory factor. A high-sensitivity method is available for the measurement of 1-hydroxypyrene in urine. There is consensus on validation of biomarkers of oxidative damage DNA based on the comet assay...

  12. Guidelines for uniform reporting of body fluid biomarker studies in neurologic disorders

    DEFF Research Database (Denmark)

    Gnanapavan, Sharmilee; Hegen, Harald; Khalil, Michael

    2014-01-01

    , there are concerns over the high attrition rate of promising candidate biomarkers at later phases of development. METHODS: BioMS-eu consortium, a collaborative network working toward improving the quality of biomarker research in neurologic disorders, discussed the merits of standardizing the reporting of body fluid...... biomarker research. A checklist of items integrating the results of other published guidances, literature, conferences, regulatory opinion, and personal expertise was created to ultimately form a structured summary guidance incorporating the key features. RESULTS: The summary guidance is comprised of a 10......-point uniform reporting format ranging from introduction, materials and methods, through to results and discussion. Each item is discussed in detail in the guidance report. CONCLUSIONS: To enhance the future development of body fluid biomarkers, it will be important to standardize the reporting...

  13. Household air pollution: a call for studies into biomarkers of exposure and predictors of respiratory disease.

    Science.gov (United States)

    Rylance, Jamie; Gordon, Stephen B; Naeher, Luke P; Patel, Archana; Balmes, John R; Adetona, Olorunfemi; Rogalsky, Derek K; Martin, William J

    2013-05-01

    Household air pollution (HAP) from indoor burning of biomass or coal is a leading global cause of morbidity and mortality, mostly due to its association with acute respiratory infection in children and chronic respiratory and cardiovascular diseases in adults. Interventions that have significantly reduced exposure to HAP improve health outcomes and may reduce mortality. However, we lack robust, specific, and field-ready biomarkers to identify populations at greatest risk and to monitor the effectiveness of interventions. New scientific approaches are urgently needed to develop biomarkers of human exposure that accurately reflect exposure or effect. In this Perspective, we describe the global need for such biomarkers, the aims of biomarker development, and the state of development of tests that have the potential for rapid transition from laboratory bench to field use.

  14. Comprehensive Study of the Model Mercury-Based Cuprate Superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Greven, Martin [Univ. of Minnesota, Minneapolis, MN (United States)

    2017-11-13

    This is the Final Report on DE-SC0006858, which opened 15 August 2011 and closed 14 August 2017. The Principal Investigator is Martin Greven, School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 555455 (email: greven@umn.edu). The Administrative Point of Contact is Patricia Jondahl, phone: 612-624-5599, email: awards@umn.edu. The DOE Program is the Office of Basic Energy Sciences, Program manager is Dr. P. Thiyagarajan, Neutron Scattering SC-22.2/ Germantown Bldg. (email: Thiyagarajan@science.doe.gov). The chief activity was the crystal growth, characterization, neutron and X-ray scattering study of the mercury-based cuprates, arguably the most desirable high-Tc superconductors for experimental study due to their record values of Tc and their relatively simple crystal structures. It is thought that the unusual magnetic and charge degrees of freedom of the copper-oxygen sheets that form the fundamental building block of all cuprate superconductors give rise to the high Tc and to many other unusual properties exhibited by the class of quantum materials. Neutron scattering experiments were performed to reveal the nature of the magnetic degrees of freedom of the copper-oxygen sheets, whereas X-ray scattering experiments and complementary charge-transport experiments were performed to reveal the nature of the charge degrees of freedom. In addition, collaborations were initiated with experts in the use of complementary experimental techniques. The primary products are (i) scientific articles published in peer-reviewed scientific journals, (ii) scientific presentations at national and international conferences, and (iii) education of postdoctoral researchers, PhD graduate students and undergraduate researchers by providing a research experience in crystal growth, characterization and scattering. Twenty scientific papers were published in peer-reviewed journals, thirty-one invited talks were presented at national or international conferences, or as

  15. Big Data in HEP: A comprehensive use case study

    Science.gov (United States)

    Gutsche, Oliver; Cremonesi, Matteo; Elmer, Peter; Jayatilaka, Bo; Kowalkowski, Jim; Pivarski, Jim; Sehrish, Saba; Mantilla Surez, Cristina; Svyatkovskiy, Alexey; Tran, Nhan

    2017-10-01

    Experimental Particle Physics has been at the forefront of analyzing the worlds largest datasets for decades. The HEP community was the first to develop suitable software and computing tools for this task. In recent times, new toolkits and systems collectively called Big Data technologies have emerged to support the analysis of Petabyte and Exabyte datasets in industry. While the principles of data analysis in HEP have not changed (filtering and transforming experiment-specific data formats), these new technologies use different approaches and promise a fresh look at analysis of very large datasets and could potentially reduce the time-to-physics with increased interactivity. In this talk, we present an active LHC Run 2 analysis, searching for dark matter with the CMS detector, as a testbed for Big Data technologies. We directly compare the traditional NTuple-based analysis with an equivalent analysis using Apache Spark on the Hadoop ecosystem and beyond. In both cases, we start the analysis with the official experiment data formats and produce publication physics plots. We will discuss advantages and disadvantages of each approach and give an outlook on further studies needed.

  16. A comprehensive experimental and modeling study of isobutene oxidation

    KAUST Repository

    Zhou, Chong-Wen; Li, Yang; O'Connor, Eoin; Somers, Kieran P.; Thion, Sé bastien; Keesee, Charles; Mathieu, Olivier; Petersen, Eric L.; DeVerter, Trent A.; Oehlschlaeger, Matthew A.; Kukkadapu, Goutham; Sung, Chih-Jen; Alrefae, Majed; Khaled, Fathi; Farooq, Aamir; Dirrenberger, Patricia; Glaude, Pierre-Alexandre; Battin-Leclerc, Fré dé rique; Santner, Jeffrey; Ju, Yiguang; Held, Timothy; Haas, Francis M.; Dryer, Frederick L.; Curran, Henry J.

    2016-01-01

    The differences in low-temperature chemistry between alkanes and alkenes are also highlighted in this work. In normal alkanes, the fuel radical Ṙ adds to molecular oxygen forming alkylperoxyl (RȮ2) radicals followed by isomerization and chain branching reactions which promote low-temperature fuel reactivity. However, in alkenes, because of the relatively shallow well (∼20 kcal mol–1) for RȮ2 formation compared to ∼35 kcal mol–1 in alkanes, the Ṙ + O2 ⇌ RȮ2 equilibrium lies more to the left favoring Ṙ + O2 rather than RȮ2 radical stabilization. Based on this work, and related studies of allylic systems, it is apparent that reactivity for alkene components at very low temperatures (<800 K) emanates from hydroxyl radical addition followed by addition of molecular oxygen to radical. At intermediate temperatures (800–1300 K), alkene reactivity is controlled by hydrogen abstraction by molecular oxygen and the reactions between resonantly stabilized radicals and hydroperoxyl radicals which results in chain branching. At higher temperatures (>1300 K), the reactivity is mainly governed by the competition between hydrogen abstractions by molecular oxygen and ȮH radicals.

  17. A comprehensive experimental and modeling study of 2-methylbutanol combustion

    KAUST Repository

    Park, Sungwoo

    2015-05-01

    2-Methylbutanol (2-methyl-1-butanol) is one of several next-generation biofuels that can be used as an alternative fuel or blending component for combustion engines. This paper presents new experimental data for 2-methylbutanol, including ignition delay times in a high-pressure shock tube and premixed laminar flame speeds in a constant volume combustion vessel. Shock tube ignition delay times were measured for 2-methylbutanol/air mixtures at three equivalence ratios, temperatures ranging from 750 to 1250. K, and at nominal pressures near 20 and 40. bar. Laminar flame speed data were obtained using the spherically propagating premixed flame configuration at pressures of 1, 2, and 5. bar. A detailed chemical kinetic model for 2-methylbutanol oxidation was developed including high- and low-temperature chemistry based on previous modeling studies on butanol and pentanol isomers. The proposed model was tested against new and existing experimental data at pressures of 1-40. atm, temperatures of 740-1636. K, equivalence ratios of 0.25-2.0. Reaction path and sensitivity analyses were conducted for identifying key reactions at various combustion conditions, and to obtain better understanding of the combustion characteristics of larger alcohols.

  18. Saint John lateral pipeline project: comprehensive study report

    International Nuclear Information System (INIS)

    1999-02-01

    A descripion is given of the results of an environmental impact assessment of the construction of a natural gas pipeline that will bring gas from Maritimes and Northeast Pipeline Management Ltd.'s (M and NP) main transmission pipeline to clients in Lake Utopia and Saint John, NB. It will be 110 km long, and the Saint John lateral will join the mainline approximately 2 km south of Big Kedron Lake, NB. Various institutional, industrial, commercial and residential clients will be able to access the pipeline in the future, and it is intended to be capable of future expansion for markets along its route and for markets that become economically feasible in the future. A matrix was developed that relates environmental resources to Environmental Components of Concern (ECCs), and to the rationale for exclusion/inclusion of the ECC as a Valued Environmental Component (VECs). The positive benefits of the pipeline to clients in the Saint John area include: reduced dependence on foreign oil, fuel switching and price competition, lower air emission pollution, increased energy efficiency, and a source of energy that is secure and reliable. VECs were selected based on: concerns of various stakeholders including the public, community groups, scientific parties, Aboriginal groups, government officials and agencies, relevant regulations; relevant literature; and past evaluation experiences, including future developments of the proposed study area. Further selection of the VECs required an examination of the issues picked out via scoping to determine the ways in which the overall project could affect the ECCs, and included construction, operation, decommissioning/abandonment, malfunctions and accidents of the pipeline. The phases of the project as they impacted residually and cumulatively on the VECs were evaluated, and impacts on Valued Socio-Economic Components (VSCs) were assessed also. The mitigation efforts taken will minimize the potential effects of the project on VECs and VSCs

  19. Performance Demands in Softball Pitching: A Comprehensive Muscle Fatigue Study.

    Science.gov (United States)

    Corben, Jeffrey S; Cerrone, Sara A; Soviero, Julie E; Kwiecien, Susan Y; Nicholas, Stephen J; McHugh, Malachy P

    2015-08-01

    Monitoring pitch count is standard practice in minor league baseball but not in softball because of the perception that fast-pitch softball pitching is a less stressful motion. To examine muscle fatigue after fast-pitch softball performances to provide an assessment of performance demand. Descriptive laboratory study. Bilateral strength measurements (handheld dynamometer) were made on 19 female softball pitchers (mean age [±SD], 15.2 ± 1.2 years) before and after pitching a game (mean number of pitches, 99 ± 21; mean innings pitched, 5 ± 1). A total of 20 tests were performed on the dominant and nondominant sides: forearm (grip, wrist flexion/extension, pronation/supination, elbow flexion/extension), shoulder (flexion, abduction/adduction, external/internal rotation, empty can test), scapula (middle/lower trapezius, rhomboid), and hip (hip flexion/extension, abduction/adduction). Fatigue (percentage strength loss) was categorized based on bilateral versus unilateral presentation using paired t tests: bilateral symmetric (significant on dominant and nondominant and not different between sides), bilateral asymmetric (significant on dominant and nondominant but significantly greater on dominant), unilateral asymmetric (significant on dominant only and significantly greater than nondominant), or unilateral equivocal (significant on dominant only but not different from nondominant). Bilateral symmetric fatigue was evident for all hip (dominant, 19.3%; nondominant, 15.2%) and scapular tests (dominant, 19.2%; nondominant, 19.3%). In general, shoulder tests exhibited bilateral asymmetric fatigue (dominant, 16.9%; nondominant, 11.6%). Forearm tests were more variable, with bilateral symmetric fatigue in the elbow flexors (dominant, 22.5%; nondominant, 19.2%), and wrist flexors (dominant, 21.6%; nondominant, 19.0%), bilateral asymmetric fatigue in the supinators (dominant, 21.8%; nondominant, 15.5%), unilateral asymmetric fatigue in the elbow extensors (dominant, 22

  20. A Study on the Comprehensive and Integrated Workplace Safety and Health Services in Singapore.

    Science.gov (United States)

    Chia, Sin Eng; Wah, Lim John; Khim, Judy Sng Gek; Yoong, Joanne; Lim, Raymond Boon Tar; Seng, Chia Kee

    2015-09-01

    The aim of this study was to evaluate the level of comprehensiveness and integration of workplace safety and health (WSH) services (safety, occupational health, and well-being) in Singapore. Thirty workplaces from five different sectors comprising more than 28,000 workers were assessed using three custom-developed tools. One quarter of the workplaces have applied the principles of comprehensive and integrated WSH. Among those that managed WSH comprehensively, workers were 4.4 times (95% confidence interval [CI], 2.33 to 8.25) more likely to be proud to work for their company, 7.4 times (95% CI, 3.96 to 13.90) more likely to be satisfied with their current job, and 1.7 times (95% CI, 1.21 to 2.32) more likely to balance the demands of work and home. There is a need to enhance awareness and education on comprehensive and integrated WSH in Singapore companies.

  1. Traumatic brain injury produced by exposure to blasts, a critical problem in current wars: biomarkers, clinical studies, and animal models

    Science.gov (United States)

    Dixon, C. Edward

    2011-06-01

    Traumatic brain injury (TBI) resulting from exposure to blast energy released by Improvised Explosive Devices (IEDs) has been recognized as the "signature injury" of Operation Iraqi Freedom and Operation Enduring Freedom. Repeated exposure to mild blasts may produce subtle deficits that are difficult to detect and quantify. Several techniques have been used to detect subtle brain dysfunction including neuropsychological assessments, computerized function testing and neuroimaging. Another approach is based on measurement of biologic substances (e.g. proteins) that are released into the body after a TBI. Recent studies measuring biomarkers in CSF and serum from patients with severe TBI have demonstrated the diagnostic, prognostic, and monitoring potential. Advancement of the field will require 1) biochemical mining for new biomarker candidates, 2) clinical validation of utility, 3) technical advances for more sensitive, portable detectors, 4) novel statistical approach to evaluate multiple biomarkers, and 5) commercialization. Animal models have been developed to simulate elements of blast-relevant TBI including gas-driven shock tubes to generate pressure waves similar to those produced by explosives. These models can reproduce hallmark clinical neuropathological responses such as neuronal degeneration and inflammation, as well as behavioral impairments. An important application of these models is to screen novel therapies and conduct proteomic, genomic, and lipodomic studies to mine for new biomarker candidates specific to blast relevant TBI.

  2. Towards a better understanding of biomarker response in field survey: a case study in eight populations of zebra mussels.

    Science.gov (United States)

    Pain-Devin, S; Cossu-Leguille, C; Geffard, A; Giambérini, L; Jouenne, T; Minguez, L; Naudin, B; Parant, M; Rodius, F; Rousselle, P; Tarnowska, K; Daguin-Thiébaut, C; Viard, F; Devin, S

    2014-10-01

    In order to provide reliable information about responsiveness of biomarkers during environmental monitoring, there is a need to improve the understanding of inter-population differences. The present study focused on eight populations of zebra mussels and aimed to describe how variable are biomarkers in different sampling locations. Biomarkers were investigated and summarised through the Integrated Biomarker Response (IBR index). Inter-site differences in IBR index were analysed through comparisons with morphological data, proteomic profiles and genetic background of the studied populations. We found that the IBR index was a good tool to inform about the status of sites. It revealed higher stress in more polluted sites than in cleaner ones. It was neither correlated to proteomic profiles nor to genetic background, suggesting a stronger influence of environment than genes. Meanwhile, morphological traits were related to both environment and genetic background influence. Together these results attest the benefit of using biological tools to better illustrate the status of a population and highlight the need of consider inter-population difference in their baselines. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. The utility of collateral student drinking reports: Evidence from a biomarker study.

    Science.gov (United States)

    Fendrich, Michael; Fuhrmann, Daniel; Berger, Lisa; Plate, Charles; Lewis, Douglas; Jones, Joseph

    2015-11-01

    Researchers have increasingly used collateral informants to validate the reports provided by primary research subjects. We assessed the utility of collateral informants for college students in a study that incorporates biomarkers to validate student reports of recent drinking behavior. Students from a Midwestern university were randomly selected for a study in which they provided 90-day Timeline Followback data, hair and fingernail specimens for ethylglucuronide (EtG) testing, and information about collateral (friends or peers) informants who were familiar with their drinking behavior. We compared summary measures of recent drinking to collateral informant reports for the subset of 72 students who were selected to participate in the collateral validation process who had complete measures. Kappa, weighted kappa, and McNemar tests were performed to evaluate levels of agreement. We compared levels of use indicated by each informant within the context of EtG findings. We also compared respondent and collateral reports with respect to heavy drinking directly to EtG test results. There was considerable overlap between the reports provided by the student participants and their collateral informants. Within the context of EtG-informed analyses, collaterals rarely provided new information about heavy use beyond that provided by the study subjects. Collateral informants have limited utility in non-clinical studies of heavy drinking in randomly selected college students. Copyright © 2015. Published by Elsevier Ltd.

  4. Elastin: a possible genetic biomarker for more severe ligament injuries in elite soccer. A pilot study

    Science.gov (United States)

    Artells, Rosa; Pruna, Ricard; Dellal, Alexandre; Maffulli, Nicola

    2016-01-01

    Summary Background The study of new genetic biomarkers in genes related to connective tissue repair and regeneration may help to identify individuals with greater predisposition to injury, who may benefit from targeted preventive measures, and those who require longer recovery time following a muscle, ligament or tendon injury. The present study investigated whether single nucleotide polymorphisms of the Elastin gene could be related to MCL injury. Methods 60 top class football players were studied to identify single nucleotide polymorphisms for the Elastin (ELN) gene using Allelic Discrimination analysis. Each player was followed for 7 seasons, and each MCL injury was noted. Results Ligament injury rate, severity and recovery time are related to specific genotypes observed in the elastin gene, especially the ELN-AA (16 MCL) and the ELN-AG (3 MCL). Players with the ELN-GG genotype sustained no MCL injury during the 7 seasons of the study. Conclusions The identification of polymorphisms in the ELN gene may be used as a novel tool to better define an athlete’s genotype, and help to plan training and rehabilitation programmes to prevent or minimize MCL ligament injuries, and optimize the therapeutic and rehabilitation process after soft tissue injuries, and manage the workloads during trainings and matches. PMID:27900291

  5. Evaluation of miR-122 as a Serum Biomarker for Hepatotoxicity in Investigative Rat Toxicology Studies.

    Science.gov (United States)

    Sharapova, T; Devanarayan, V; LeRoy, B; Liguori, M J; Blomme, E; Buck, W; Maher, J

    2016-01-01

    MicroRNAs are short noncoding RNAs involved in regulation of gene expression. Certain microRNAs, including miR-122, seem to have ideal properties as biomarkers due to good stability, high tissue specificity, and ease of detection across multiple species. Recent reports have indicated that miR-122 is a highly liver-specific marker detectable in serum after liver injury. The purpose of the current study was to assess the performance of miR-122 as a serum biomarker for hepatotoxicity in short-term (5-28 days) repeat-dose rat toxicology studies when benchmarked against routine clinical chemistry and histopathology. A total of 23 studies with multiple dose levels of experimental compounds were examined, and they included animals with or without liver injury and with various hepatic histopathologic changes. Serum miR-122 levels were quantified by reverse transcription quantitative polymerase chain reaction. Increases in circulating miR-122 levels highly correlated with serum elevations of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Statistical analysis showed that miR-122 outperformed ALT as a biomarker for histopathologically confirmed liver toxicity and was equivalent in performance to AST and GLDH. Additionally, an increase of 4% in predictive accuracy was obtained using a multiparameter approach incorporating miR-122 with ALT, AST, and GLDH. In conclusion, serum miR-122 levels can be utilized as a biomarker of hepatotoxicity in acute and subacute rat toxicology studies, and its performance can rival or exceed those of standard enzyme biomarkers such as the liver transaminases. © The Author(s) 2015.

  6. The use of biomarkers to assess the health of aquatic ecosystems in Brazil: a review

    Directory of Open Access Journals (Sweden)

    Thaís Dalzochio

    2016-11-01

    Full Text Available Abstract Organisms in polluted environments are typically exposed to a complex mixture of chemical contaminants. The great concern about the health of aquatic ecosystems has led to the increased use of biomarkers over the past years. The aim of this work was to review the papers published from 2000 to 2015, which used biomarkers to assess the health of aquatic ecosystems in Brazil. A research resulted in 99 eligible papers. More than 80% of studies were conducted in the states of São Paulo and Rio Grande do Sul. Approximately 63% of studies used fish as bioindicator, whereas the micronucleus test and biochemical analyses were the most used biomarkers. A multibiomarker approach was used by 60.6% of studies, while 39.4% used one single biomarker. Furthermore, 68% were field studies and more than 75% of these used control animals sampled at reference sites. A relationship between the biomarker responses and pollution was reported by 87% of studies; however, 43.4% of studies analyzed only one sampling period, limiting comparisons and comprehension about possible seasonal variations. This review evidenced some weak points in studies using biomarkers in Brazil, especially related to the lack of studies in two important biomes (the Pantanal and the Amazon Rainforest and experimental designs (small sample size, sampling in one single period, use of one single biomarker. Thus, future studies should consider mainly the use of multiple biomarkers, greater sample size, seasonal sampling and water physicochemical parameters to better diagnose the health of aquatic ecosystems.

  7. A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas

    Directory of Open Access Journals (Sweden)

    Kampf Caroline

    2012-09-01

    Full Text Available Abstract The complexity of tissue and the alterations that distinguish normal from cancer remain a challenge for translating results from tumor biological studies into clinical medicine. This has generated an unmet need to exploit the findings from studies based on cell lines and model organisms to develop, validate and clinically apply novel diagnostic, prognostic and treatment predictive markers. As one step to meet this challenge, the Human Protein Atlas project has been set up to produce antibodies towards human protein targets corresponding to all human protein coding genes and to map protein expression in normal human tissues, cancer and cells. Here, we present a dictionary based on microscopy images created as an amendment to the Human Protein Atlas. The aim of the dictionary is to facilitate the interpretation and use of the image-based data available in the Human Protein Atlas, but also to serve as a tool for training and understanding tissue histology, pathology and cell biology. The dictionary contains three main parts, normal tissues, cancer tissues and cells, and is based on high-resolution images at different magnifications of full tissue sections stained with H & E. The cell atlas is centered on immunofluorescence and confocal microscopy images, using different color channels to highlight the organelle structure of a cell. Here, we explain how this dictionary can be used as a tool to aid clinicians and scientists in understanding the use of tissue histology and cancer pathology in diagnostics and biomarker studies.

  8. Biomarkers of Pediatric Brain Tumors

    Directory of Open Access Journals (Sweden)

    Mark D Russell

    2013-03-01

    Full Text Available Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as CA 19-9 and CA 125 facilitate early diagnosis and treatment. Aim: The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. Methods: A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type (serum, cerebrospinal fluid or urine, biomarkers analyzed, methodology, tumor type and statistical significance were recorded. Results: A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from cerebrospinal fluid, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups.Conclusions: This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered.

  9. Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.

    Science.gov (United States)

    de Almeida, Sergio M; Rotta, Indianara; Ribeiro, Clea E; Oliveira, Michelli F; Chaillon, Antoine; de Pereira, Ana Paula; Cunha, Ana Paula; Zonta, Marise; Bents, Joao França; Raboni, Sonia M; Smith, Davey; Letendre, Scott; Ellis, Ronald J

    2017-06-01

    Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

  10. Do classic blood biomarkers of JSLE identify active lupus nephritis? Evidence from the UK JSLE Cohort Study.

    Science.gov (United States)

    Smith, E M D; Jorgensen, A L; Beresford, M W

    2017-10-01

    Background Lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus (JSLE) patients. The value of commonly available biomarkers, such as anti-dsDNA antibodies, complement (C3/C4), ESR and full blood count parameters in the identification of active LN remains uncertain. Methods Participants from the UK JSLE Cohort Study, aged modeling, with stepAIC function applied to select a final model. Receiver-operating curve analysis was used to assess diagnostic accuracy. Results A total of 370 patients were recruited; 191 (52%) had active LN and 179 (48%) had inactive LN. Binary logistic regression modeling demonstrated a combination of ESR, C3, white cell count, neutrophils, lymphocytes and IgG to be best for the identification of active LN (area under the curve 0.724). Conclusions At best, combining common classic blood biomarkers of lupus activity using multivariate analysis provides a 'fair' ability to identify active LN. Urine biomarkers were not included in these analyses. These results add to the concern that classic blood biomarkers are limited in monitoring discrete JSLE manifestations such as LN.

  11. Prognostic biomarkers in osteoarthritis

    Science.gov (United States)

    Attur, Mukundan; Krasnokutsky-Samuels, Svetlana; Samuels, Jonathan; Abramson, Steven B.

    2013-01-01

    Purpose of review Identification of patients at risk for incident disease or disease progression in osteoarthritis remains challenging, as radiography is an insensitive reflection of molecular changes that presage cartilage and bone abnormalities. Thus there is a widely appreciated need for biochemical and imaging biomarkers. We describe recent developments with such biomarkers to identify osteoarthritis patients who are at risk for disease progression. Recent findings The biochemical markers currently under evaluation include anabolic, catabolic, and inflammatory molecules representing diverse biological pathways. A few promising cartilage and bone degradation and synthesis biomarkers are in various stages of development, awaiting further validation in larger populations. A number of studies have shown elevated expression levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma). These chemical biomarkers are under evaluation in combination with imaging biomarkers to predict early onset and the burden of disease. Summary Prognostic biomarkers may be used in clinical knee osteoarthritis to identify subgroups in whom the disease progresses at different rates. This could facilitate our understanding of the pathogenesis and allow us to differentiate phenotypes within a heterogeneous knee osteoarthritis population. Ultimately, such findings may help facilitate the development of disease-modifying osteoarthritis drugs (DMOADs). PMID:23169101

  12. CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

    Science.gov (United States)

    Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S.; Toledo, Jon B.; Weintraub, Daniel; Galasko, Douglas R.; Irwin, David J.; Van Deerlin, Vivianna; Chen-Plotkin, Alice S.; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M.; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Trojanowski, John Q.; Shaw, Leslie M.

    2016-01-01

    The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1–42 (Aβ1–42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1–42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1–42, or highest t-tau/Aβ1–42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1–42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

  13. Candidate proteins, metabolites and transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA clinical study.

    Directory of Open Access Journals (Sweden)

    Richard S Finkel

    Full Text Available Spinal Muscular Atrophy (SMA is a neurodegenerative motor neuron disorder resulting from a homozygous mutation of the survival of motor neuron 1 (SMN1 gene. The gene product, SMN protein, functions in RNA biosynthesis in all tissues. In humans, a nearly identical gene, SMN2, rescues an otherwise lethal phenotype by producing a small amount of full-length SMN protein. SMN2 copy number inversely correlates with disease severity. Identifying other novel biomarkers could inform clinical trial design and identify novel therapeutic targets.To identify novel candidate biomarkers associated with disease severity in SMA using unbiased proteomic, metabolomic and transcriptomic approaches.A cross-sectional single evaluation was performed in 108 children with genetically confirmed SMA, aged 2-12 years, manifesting a broad range of disease severity and selected to distinguish factors associated with SMA type and present functional ability independent of age. Blood and urine specimens from these and 22 age-matched healthy controls were interrogated using proteomic, metabolomic and transcriptomic discovery platforms. Analyte associations were evaluated against a primary measure of disease severity, the Modified Hammersmith Functional Motor Scale (MHFMS and to a number of secondary clinical measures.A total of 200 candidate biomarkers correlate with MHFMS scores: 97 plasma proteins, 59 plasma metabolites (9 amino acids, 10 free fatty acids, 12 lipids and 28 GC/MS metabolites and 44 urine metabolites. No transcripts correlated with MHFMS.In this cross-sectional study, "BforSMA" (Biomarkers for SMA, candidate protein and metabolite markers were identified. No transcript biomarker candidates were identified. Additional mining of this rich dataset may yield important insights into relevant SMA-related pathophysiology and biological network associations. Additional prospective studies are needed to confirm these findings, demonstrate sensitivity to change with

  14. Metabolic and inflammatory profiles of biomarkers in obesity, metabolic syndrome, and diabetes in a Mediterranean population. DARIOS Inflammatory study.

    Science.gov (United States)

    Fernández-Bergés, Daniel; Consuegra-Sánchez, Luciano; Peñafiel, Judith; Cabrera de León, Antonio; Vila, Joan; Félix-Redondo, Francisco Javier; Segura-Fragoso, Antonio; Lapetra, José; Guembe, María Jesús; Vega, Tomás; Fitó, Montse; Elosua, Roberto; Díaz, Oscar; Marrugat, Jaume

    2014-08-01

    There is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus. We performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus. A total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated. There are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  15. Zinc Status Biomarkers and Cardiometabolic Risk Factors in Metabolic Syndrome: A Case Control Study

    Directory of Open Access Journals (Sweden)

    Erika P. S. Freitas

    2017-02-01

    Full Text Available Metabolic syndrome (MS involves pathophysiological alterations that might compromise zinc status. The aim of this study was to evaluate zinc status biomarkers and their associations with cardiometabolic factors in patients with MS. Our case control study included 88 patients with MS and 37 controls. We performed clinical and anthropometric assessments and obtained lipid, glycemic, and inflammatory profiles. We also evaluated zinc intake, plasma zinc, erythrocyte zinc, and 24-h urinary zinc excretion. The average zinc intake was significantly lower in the MS group (p < 0.001. Regression models indicated no significant differences in plasma zinc concentration (all p > 0.05 between the two groups. We found significantly higher erythrocyte zinc concentration in the MS group (p < 0.001 independent from co-variable adjustments. Twenty-four hour urinary zinc excretion was significantly higher in the MS group (p = 0.008, and adjustments for age and sex explained 21% of the difference (R2 = 0.21, p < 0.001. There were significant associations between zincuria and fasting blood glucose concentration (r = 0.479, waist circumference (r = 0.253, triglyceride concentration (r = 0.360, glycated hemoglobin concentration (r = 0.250, homeostatic model assessment—insulin resistance (r = 0.223, and high-sensitivity C-reactive protein concentration (r = 0.427 (all p < 0.05 in the MS group. Patients with MS had alterations in zinc metabolism mainly characterized by an increase in erythrocyte zinc and higher zincuria.

  16. Sensitivity analysis for publication bias in meta-analysis of diagnostic studies for a continuous biomarker.

    Science.gov (United States)

    Hattori, Satoshi; Zhou, Xiao-Hua

    2018-02-10

    Publication bias is one of the most important issues in meta-analysis. For standard meta-analyses to examine intervention effects, the funnel plot and the trim-and-fill method are simple and widely used techniques for assessing and adjusting for the influence of publication bias, respectively. However, their use may be subjective and can then produce misleading insights. To make a more objective inference for publication bias, various sensitivity analysis methods have been proposed, including the Copas selection model. For meta-analysis of diagnostic studies evaluating a continuous biomarker, the summary receiver operating characteristic (sROC) curve is a very useful method in the presence of heterogeneous cutoff values. To our best knowledge, no methods are available for evaluation of influence of publication bias on estimation of the sROC curve. In this paper, we introduce a Copas-type selection model for meta-analysis of diagnostic studies and propose a sensitivity analysis method for publication bias. Our method enables us to assess the influence of publication bias on the estimation of the sROC curve and then judge whether the result of the meta-analysis is sufficiently confident or should be interpreted with much caution. We illustrate our proposed method with real data. Copyright © 2017 John Wiley & Sons, Ltd.

  17. The use of genotoxicity biomarkers in molecular epidemiology: applications in environmental, occupational and dietary studies

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2017-08-01

    Full Text Available Molecular epidemiology is an approach increasingly used in the establishment of associations between exposure to hazardous substances and development of disease, including the possible modulation by genetic susceptibility factors. Environmental chemicals and contaminants from anthropogenic pollution of air, water and soil, but also originating specifically in occupational contexts, are potential sources of risk of development of disease. Also, diet presents an important role in this process, with some well characterized associations existing between nutrition and some types of cancer. Genotoxicity biomarkers allow the detection of early effects that result from the interaction between the individual and the environment; they are therefore important tools in cancer epidemiology and are extensively used in human biomonitoring studies. This work intends to give an overview of the potential for genotoxic effects assessment, specifically with the cytokinesis blocked micronucleus assay and comet assay in environmental and occupational scenarios, including diet. The plasticity of these techniques allows their inclusion in human biomonitoring studies, adding important information with the ultimate aim of disease prevention, in particular cancer, and so it is important that they be included as genotoxicity assays in molecular epidemiology.

  18. Lipid biomarkers for bacterial ecosystems: studies of cultured organisms, hydrothermal environments and ancient sediments

    Science.gov (United States)

    Summons, R. E.; Jahnke, L. L.; Simoneit, B. R.

    1996-01-01

    This paper forms part of our long-term goal of using molecular structure and carbon isotopic signals preserved as hydrocarbons in ancient sediments to improve understanding of the early evolution of Earth's surface environment. We are particularly concerned with biomarkers which are informative about aerobiosis. Here, we combine bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems to construct models for the nature, behaviour and preservation potential of primitive microbial communities. We use a combined molecular and isotopic approach to characterize lipids produced by cultured bacteria and test a variety of culture conditions which affect their biosynthesis. This information is then compared with lipid mixtures isolated from contemporary hot springs and evaluated for the kinds of chemical change that would accompany burial and incorporation into the sedimentary record. In this study we have shown that growth temperature does not appear to alter isotopic fractionation within the lipid classes produced by a methanotropic bacterium. We also found that cultured cyanobacteria biosynthesize diagnostic methylalkanes and dimethylalkanes with the latter only made when growing under low pCO2. In an examination of a microbial mat sample from Octopus Spring, Yellowstone National Park (USA), we could readily identify chemical structures with 13C contents which were diagnostic for the phototrophic organisms such as cyanobacteria and Chloroflexus. We could not, however, find molecular evidence for operation of a methane cycle in the particular mat samples we studied.

  19. [A surveillance study on CRISPR/Cas molecular biomarker in Escherichia coli].

    Science.gov (United States)

    Liang, W J; Zhang, R G; Duan, G C; Hong, L J; Zhang, B; Xi, Y L; Yang, H Y; Chen, S Y; Lou, T Y; Zhao, Y X

    2016-08-10

    A new method related to molecular biomarker with CRISPR/Cas (clustered regularly interspaced short palindromic repeats-cas) in Escherichia (E.) coli was developed and used for surveillance programs. CRISPR/Cas sequence that containing 135 strains with complete sequence and 203 strains with whole genome shotgun sequence of E. coli in GenBank by BLAST and 361 strains of E. coli (including 38 strains of E. coli O157∶H7) in laboratory were identified by PCR and analyzed with the CRISPR Finder. Spacers were compared with DANMAN and the phylogenetic trees of cas gene were constructed under Clustal Ⅹ and Mega 5.1. With new perspective, a descriptive method was developed targeting on the position of CRISPR/cas in E. coli. The CRISPR1 was detected in 77.04%, 100.00% and 75.62% and the CRISPR2 was detected in 74.81%, 100.00% and 92.24% and the CRISPR3 and CRISPR4 were detected in 11.85%, 0 and 1.39% for 135 strains with complete sequence, 203 strains with whole genome shotgun sequence and 361 strains in the laboratory, respectively. One strain downloaded in GenBank with whole genome sequencing and 2 strains in the our laboratory were identified that containing four CRISPR locus. The other E. coli strain was with insertion sequence in downstream of the non-cas CRISPR1. The unique CRISPR was found in 8 strains of O55∶H7, in 180 strains of O157∶H7, in 8 strains of O157∶HNM, in 40 strains of O104∶H4, in 4 strains of O145∶H28, in all the 699 E. coli strains. The phylogenetic tree could be divided into two groups-cas with type I-E or type I-F. CRISPR/Cas might be used as a valuable molecular biomarker in epidemiological surveillance studies to identify the high virulent strains or new strains of E. coli. Phage night be related to the missing or obtaining of spacers.

  20. A Case Study of the Impact of Guided Reading Groups in Second Grade on Comprehension Improvement

    Science.gov (United States)

    Lorent Deegan, Chanin E.

    2010-01-01

    This study combined both qualitative and quantitative research to determine the impact of instructional practices on comprehension improvement in second grade Guided Reading groups. Four second grade teachers and their 73 students ages seven through eight years old participated in this study. Additionally, the study examined the effects of Guided…

  1. Diagnostic accuracy for apical and chronic periodontitis biomarkers in gingival crevicular fluid: an exploratory study.

    Science.gov (United States)

    Baeza, Mauricio; Garrido, Mauricio; Hernández-Ríos, Patricia; Dezerega, Andrea; García-Sesnich, Jocelyn; Strauss, Franz; Aitken, Juan Pablo; Lesaffre, Emmanuel; Vanbelle, Sophie; Gamonal, Jorge; Brignardello-Petersen, Romina; Tervahartiala, Taina; Sorsa, Timo; Hernández, Marcela

    2016-01-01

    The aim of this study was to assess the levels and diagnostic accuracy of a set of potential biomarkers of periodontal tissue metabolism in gingival crevicular fluid (GCF) from patients with chronic periodontitis (CP) and asymptomatic apical periodontitis ( AAP). Thirty one GCF samples from 11 CP patients, 44 GCF samples from 38 AAP patients and 31 GCF samples from 13 healthy volunteers were obtained (N = 106). Matrix metalloproteinases (MMPs) -2 and -9 were determined by zymography; levels of MMP-8 by ELISA and IFMA and MPO by ELISA. IL-1, IL-6, TNFα, DKK-1, Osteonectin, Periostin, TRAP-5 and OPG were determined by a multiplex quantitative panel. Statistical analysis was performed using linear mixed-effects models. The MMP-9 and MMP-8 were higher in CP, followed by AAP, versus healthy individuals (p 0.97) in CP, and for the active form of MMP-9 and MMP-8 (AUC > 0.90) in AAP. Gingival crevicular fluid composition is modified by CP and AAP. MMP-9 and MMP-8 show diagnostic potential for CP and AAP, whereas MMP-2 and TRAP-5 are useful only for CP. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Proverb comprehension in context: a developmental study with children and adolescents.

    Science.gov (United States)

    Nippold, M A; Martin, S A; Erskine, B J

    1988-03-01

    Although previous studies have reported that proverb comprehension remains quite literal before adolescence, the results of the present study indicated that fourth graders performed well on a proverb comprehension task involving contextual information and a written multiple choice format. It was also found that performance on the proverb task steadily improved at least through the eighth grade and was significantly correlated to performance on a perceptual analogical reasoning task. The study contributes to the small but growing body of information concerning language development during the preadolescent and adolescent years and may have some important implications for the assessment of youngsters of this age range who have comprehension deficits that are troublesome, yet difficult to document.

  3. Getting the Joke: Insight during Humor Comprehension - Evidence from an fMRI Study.

    Science.gov (United States)

    Tian, Fang; Hou, Yuling; Zhu, Wenfeng; Dietrich, Arne; Zhang, Qinglin; Yang, Wenjing; Chen, Qunlin; Sun, Jiangzhou; Jiang, Qiu; Cao, Guikang

    2017-01-01

    As a high-level cognitive activity, humor comprehension requires incongruity detection and incongruity resolution, which then elicits an insight moment. The purpose of the study was to explore the neural basis of humor comprehension, particularly the moment of insight, by using both characters and language-free cartoons in a functional magnetic resonance imaging study. The results showed that insight involving jokes elicited greater activation in language and semantic-related brain regions as well as a variety of additional regions, such as the superior frontal gyrus (SFG), the inferior frontal gyrus (IFG), the middle temporal gyrus (MTG), the superior temporal gyrus (STG), the temporoparietal junctions (TPJ), the hippocampus and visual areas. These findings indicate that the MTG might play a role in incongruity detection, while the SFG, IFG and the TPJ might be involved in incongruity detection. The passive insight event elicited by jokes appears to be mediated by a limited number of brain areas. Our study showed that the brain regions associated with humor comprehension were not affected by the type of stimuli and that humor and insight shared common brain areas. These results indicate that one experiences a feeling of insight during humor comprehension, which contributes to the understanding of humor comprehension.

  4. Biomarkers of exposure in environment-wide association studies - Opportunities to decode the exposome using human biomonitoring data.

    Science.gov (United States)

    Steckling, Nadine; Gotti, Alberto; Bose-O'Reilly, Stephan; Chapizanis, Dimitris; Costopoulou, Danae; De Vocht, Frank; Garí, Mercè; Grimalt, Joan O; Heath, Ester; Hiscock, Rosemary; Jagodic, Marta; Karakitsios, Spyros P; Kedikoglou, Kleopatra; Kosjek, Tina; Leondiadis, Leondios; Maggos, Thomas; Mazej, Darja; Polańska, Kinga; Povey, Andrew; Rovira, Joaquim; Schoierer, Julia; Schuhmacher, Marta; Špirić, Zdravko; Stajnko, Anja; Stierum, Rob; Tratnik, Janja Snoj; Vassiliadou, Irene; Annesi-Maesano, Isabella; Horvat, Milena; Sarigiannis, Dimosthenis A

    2018-07-01

    The European Union's 7th Framework Programme (EU's FP7) project HEALS - Health and Environment-wide Associations based on Large Population Surveys - aims a refinement of the methodology to elucidate the human exposome. Human biomonitoring (HBM) provides a valuable tool for understanding the magnitude of human exposure from all pathways and sources. However, availability of specific biomarkers of exposure (BoE) is limited. The objective was to summarize the availability of BoEs for a broad range of environmental stressors and exposure determinants and corresponding reference and exposure limit values and biomonitoring equivalents useful for unraveling the exposome using the framework of environment-wide association studies (EWAS). In a face-to-face group discussion, scope, content, and structure of the HEALS deliverable "Guidelines for appropriate BoE selection for EWAS studies" were determined. An expert-driven, distributed, narrative review process involving around 30 individuals of the HEALS consortium made it possible to include extensive information targeted towards the specific characteristics of various environmental stressors and exposure determinants. From the resulting 265 page report, targeted information about BoE, corresponding reference values (e.g., 95th percentile or measures of central tendency), exposure limit values (e.g., the German HBM I and II values) and biomonitoring equivalents (BEs) were summarized and updated. 64 individual biological, chemical, physical, psychological and social environmental stressors or exposure determinants were included to fulfil the requirements of EWAS. The list of available BoEs is extensive with a number of 135; however, 12 of the stressors and exposure determinants considered do not leave any measurable specific substance in accessible body specimens. Opportunities to estimate the internal exposure stressors not (yet) detectable in human specimens were discussed. Data about internal exposures are useful to decode

  5. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs. A report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

    Energy Technology Data Exchange (ETDEWEB)

    Hagmar, Lars; Stroemberg, Ulf; Mikoczy, Zoli; Tinnerberg, Hakan; Skerfving, Staffan [Department of Occupational and Environmental Medicine, Lund University, S-221 85 Lund (Sweden); Bonassi, Stefano; Lando, Cecilia [Department of Environmental Epidemiology, Istituto Nazionale per la Ricerca sul Cancro, Viale Benedetto XV, I-1016132 Genoa (Italy); Hansteen, Inger-Lise [Department of Occupational Medicine, Telemark Central Hospital, N-3710 Skien (Norway); Montagud, Alicia Huici [Centro Nacional de Condiciones de Trabajo, Instituto Nacional de Seguridad e Higiene en el Trabajo, Dulcet 2-10, ES-08034 Barcelona (Spain); Knudsen, Lisbeth [National Institute of Occupational Health, Lersoe Parkalle 105, DK-2100 Copenhagen (Denmark); Norppa, Hannu [Finnish Institute of Occupational Health, Topeliuksekatu 41 aA, FIN-00250 Helsinki (Finland); Reuterwall, Christina [National Institute of Work Life, S-171 84 Solna (Sweden); Broegger, Anton [Norwegian Radium Hospital, Oslo (Norway); Forni, Alessandra [Istituto di Medicina del Lavoro Clinica del Lavoro `L. Devoto`, Milan (Italy); Hoegstedt, Benkt [Department of Occupational Medicine, Central Hospital, Halmstad (Sweden); Lambert, Bo [Department of Environmental Medicine, Centre for Nutrition and Toxicology, Karolinska Institute, Stockholm (Sweden); Mitelman, Felix [Department of Clinical Genetics, Lund University, Lund (Sweden); Nordenson, Ingrid [National Institute of Work Life, Umea (Sweden); Salomaa, Sisko [Finnish Center for Radiation and Nuclear Safety, Helsinki (Finland)

    1998-09-20

    The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base

  6. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs. A report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

    International Nuclear Information System (INIS)

    Hagmar, Lars; Stroemberg, Ulf; Mikoczy, Zoli; Tinnerberg, Hakan; Skerfving, Staffan; Bonassi, Stefano; Lando, Cecilia; Hansteen, Inger-Lise; Montagud, Alicia Huici; Knudsen, Lisbeth; Norppa, Hannu; Reuterwall, Christina; Broegger, Anton; Forni, Alessandra; Hoegstedt, Benkt; Lambert, Bo; Mitelman, Felix; Nordenson, Ingrid; Salomaa, Sisko

    1998-01-01

    The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base

  7. Metabolites as Biomarkers of Adverse Reactions Following Vaccination: A Pilot Study using Nuclear Magnetic Resonance Metabolomics

    Science.gov (United States)

    McClenathan, Bruce M.; Stewart, Delisha A.; Spooner, Christina E.; Pathmasiri, Wimal W.; Burgess, Jason P.; McRitchie, Susan L.; Choi, Y. Sammy; Sumner, Susan C.J.

    2017-01-01

    An Adverse Event Following Immunization (AEFI) is an adverse reaction to a vaccination that goes above and beyond the usual side effects associated with vaccinations. One serious AEFI related to the smallpox vaccine is myopericarditis. Metabolomics involves the study of the low molecular weight metabolite profile of cells, tissues, and biological fluids, and provides a functional readout of the phenotype. Metabolomics may help identify a particular metabolic signature in serum of subjects who are predisposed to developing AEFIs. The goal of this study was to identify metabolic markers that may predict the development of adverse events following smallpox vaccination. Serum samples were collected from military personnel prior to and following receipt of smallpox vaccine. The study population included five subjects who were clinically diagnosed with myopericarditis, 30 subjects with asymptomatic elevation of troponins, and 31 subjects with systemic symptoms following immunization, and 34 subjects with no AEFI, serving as controls. Two-hundred pre- and post-smallpox vaccination sera were analyzed by untargeted metabolomics using 1H nuclear magnetic resonance (NMR) spectroscopy. Baseline (pre-) and post-vaccination samples from individuals who experienced clinically verified myocarditis or asymptomatic elevation of troponins were more metabolically distinguishable pre- and post-vaccination compared to individuals who only experienced systemic symptoms, or controls. Metabolomics profiles pre- and post-receipt of vaccine differed substantially when an AEFI resulted. This study is the first to describe pre- and post-vaccination metabolic profiles of subjects who developed an adverse event following immunization. The study demonstrates the promise of metabolites for determining mechanisms associated with subjects who develop AEFI and the potential to develop predictive biomarkers. PMID:28169076

  8. Urinary Proteomics Pilot Study for Biomarker Discovery and Diagnosis in Heart Failure with Reduced Ejection Fraction

    DEFF Research Database (Denmark)

    Rossing, Kasper; Bosselmann, Helle Skovmand; Gustafsson, Finn

    2016-01-01

    and Results Urine samples were analyzed by on-line capillary electrophoresis coupled to electrospray ionization micro time-of-flight mass spectrometry (CE-MS) to generate individual urinary proteome profiles. In an initial biomarker discovery cohort, analysis of urinary proteome profiles from 33 HFr......Background Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF) may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF. Methods.......6%) in individuals with diastolic left ventricular dysfunction (N = 176). The HFrEF-related peptide biomarkers mainly included fragments of fibrillar type I and III collagen but also, e.g., of fibrinogen beta and alpha-1-antitrypsin. Conclusion CE-MS based urine proteome analysis served as a sensitive tool...

  9. Bias in emerging biomarkers for bipolar disorder

    DEFF Research Database (Denmark)

    Carvalho, A F; Köhler, C A; Fernandes, B S

    2016-01-01

    BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed/Medline, E...

  10. A Selected Reaction Monitoring Mass Spectrometry Protocol for Validation of Proteomic Biomarker Candidates in Studies of Psychiatric Disorders.

    Science.gov (United States)

    Reis-de-Oliveira, Guilherme; Garcia, Sheila; Guest, Paul C; Cassoli, Juliana S; Martins-de-Souza, Daniel

    2017-01-01

    Most biomarker candidates arising from proteomic studies of psychiatric disorders have not progressed for use in clinical studies due to insufficient validation steps. Here we describe a selective reaction monitoring mass spectrometry (SRM-MS) approach that could be used as a follow-up validation tool of proteins identified in blood serum or plasma. This protocol specifically covers the stages of peptide selection and optimization. The increasing application of SRM-MS should enable fast, sensitive, and robust methods with the potential for use in clinical studies involving sampling of serum or plasma. Understanding the molecular mechanisms and identifying potential biomarkers for risk assessment, diagnosis, prognosis, and prediction of drug response goes toward the implementation of translational medicine strategies for improved treatment of patients with psychiatric disorders and other debilitating diseases.

  11. Protein biomarkers on tissue as imaged via MALDI mass spectrometry: A systematic approach to study the limits of detection.

    Science.gov (United States)

    van de Ven, Stephanie M W Y; Bemis, Kyle D; Lau, Kenneth; Adusumilli, Ravali; Kota, Uma; Stolowitz, Mark; Vitek, Olga; Mallick, Parag; Gambhir, Sanjiv S

    2016-06-01

    MALDI mass spectrometry imaging (MSI) is emerging as a tool for protein and peptide imaging across tissue sections. Despite extensive study, there does not yet exist a baseline study evaluating the potential capabilities for this technique to detect diverse proteins in tissue sections. In this study, we developed a systematic approach for characterizing MALDI-MSI workflows in terms of limits of detection, coefficients of variation, spatial resolution, and the identification of endogenous tissue proteins. Our goal was to quantify these figures of merit for a number of different proteins and peptides, in order to gain more insight in the feasibility of protein biomarker discovery efforts using this technique. Control proteins and peptides were deposited in serial dilutions on thinly sectioned mouse xenograft tissue. Using our experimental setup, coefficients of variation were biomarkers and a new benchmarking strategy that can be used for comparing diverse MALDI-MSI workflows. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. A Correlation Study between EFL Strategic Listening and Listening Comprehension Skills among Secondary School Students

    Science.gov (United States)

    Amin, Iman Abdul-Reheem; Amin, Magdy Mohammad; Aly, Mahsoub Abdul-Sadeq

    2011-01-01

    The present study was undertaken to investigate the correlation between EFL students strategic listening and their listening comprehension skills. Eighty secondary school students participated in this study. Participants' strategic listening was measured by a Strategic Listening Interview (SLI), a Strategic Listening Questionnaire (SLQ) and a…

  13. Promoting Acceleration of Comprehension and Content through Text in High School Social Studies Classes

    Science.gov (United States)

    Wanzek, Jeanne; Swanson, Elizabeth A.; Roberts, Greg; Vaughn, Sharon; Kent, Shawn C.

    2015-01-01

    The purpose of this study was to evaluate the efficacy of Promoting Acceleration of Comprehension and Content Through Text intervention implemented with 11th-grade students enrolled in U.S. History classes. Using a within-teacher randomized design, the study was conducted in 41 classes (23 treatment classes) with 14 teachers providing the…

  14. An Exploratory Study of NNES Graduate Students' Reading Comprehension of English Journal Articles

    Science.gov (United States)

    Chen, Kate Tzu-Ching

    2017-01-01

    The academic success of non-native English speaker (NNES) graduate students greatly relies on their ability to read and comprehend English journal articles (EJA). The purpose of this study was to identify NNES graduate students' comprehension difficulties and reading strategies when reading EJA. In addition, the study explored how the relationship…

  15. Exploring the Causes of Listening Comprehension Anxiety from EFL Saudi Learners’ Perspectives: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Ibrahim Otair

    2017-08-01

    Full Text Available Anxiety is an important factor in foreign language learning. Very few studies have been done on English as a Foreign Language (EFL Saudi students in listening classes. Therefore, this pilot study was aimed at exploring the causes of listening comprehension anxiety from EFL Saudi learners’ perspectives at Majmaah University, Saudi Arabia. The pilot study involved two students who were selected based on the following criteria: 1 Only Saudi male undergraduate students who enrolled in Preparatory Year Program (PYP at Majmaah University would be involved in this study, 2 The students who had studied or lived in native English speaking countries would be excluded. The researcher used pseudonyms to refer to the participants as Mohammad and Ismail. This study employed a qualitative case study research design. The data were collected through Semi-structured interviews with the participants. The interview sessions were audiotaped and transcribed. The results show that the participants experienced a high level of anxiety when doing the listening comprehension tasks. Three main causes of listening comprehension anxiety emerged from this study: 1 the problematic nature of listening comprehension, 2 the classroom atmosphere, and 3 the low English proficiency of the students.

  16. Pilot Study on the Investigation of Tear Fluid Biomarkers as an Indicator of Ocular, Neurological, and Immunological Health in Astronauts

    Science.gov (United States)

    Morton, Stephen; Crucian, Brian; Hagan, Suzanne; Satyamitra, Merriline; Daily, Anna

    2018-01-01

    The purpose of this pilot study is to investigate the collection, preparation, and analysis of tear biomarkers as a means of assessing ocular, neurological, and immunological health. At present, no published data exists on the cytokine profiles of tears from astronauts exposed to long periods of microgravity and space irradiations. In addition, no published data exist on cytokine (biomarker) profiles of tears that have been collected from irradiated non-human biological systems (primates and other animal models). A goal for the proposed pilot study is to discover novel tear biomarkers which can help inform researchers, clinicians, epidemiologist and healthcare providers about the health status of a living biological system, as well as informing them when a disease state is triggered. This would be done via analysis of the onset of expression of pro-inflammatory cytokines, leading up to the full progression of a disease (i.e. cancer, loss of vision, radiation-induced oxidative stress, cardiovascular disorders, fibrosis in major organs, bone loss). Another goal of this pilot study is to investigate the state of disease against proposed medical countermeasures, in order to determine whether the countermeasures are efficacious in preventing or mitigating these injuries. An example of an up and coming tear biomarker technology, Ascendant Dx, a clinical stage diagnostic company, is developing a screening test to detect breast cancer using proteins from tears. The team utilized Liquid Chromatography -Mass Spectrometry with Mass analysis (LC MS/MS) as a discovery platform followed by validation with ELISA to come up with a panel of protein biomarkers that can differentiate breast cancer samples from control ("cancer free") samples with results far surpassing the results of imaging techniques in use today. Continued research into additional proteins is underway to increase the sensitivity and specificity of the test and development efforts are on the way to transfer the

  17. Impact of Nursery Rhymes on Iranian EFL Learners’ Listening Comprehension Skill Improvement-A Study

    Directory of Open Access Journals (Sweden)

    Omid Pourkalhor

    2017-06-01

    Full Text Available The present study was an attempt to investigate the effect of nursery rhymes on the young language learners listening comprehension ability. To do so, 30 elementary learners were selected as the potential participants of the study. The learners’ perceptions about using nursery rhymes in teaching listening as well as teachers’ perceptions about teaching listening comprehension through nursery rhymes were taken into account. The listening pre- and post-tests and teachers and learners’ interviews were employed for data collection procedures. Quantitative as well as qualitative methodologies were adapted for data analysis. Findings showed that the young learners could improve their listening comprehension ability as a result of using nursery rhymes. Interview data also indicated that the learners’ perceptions about nursery rhymes were found to be positive since the rhymes provided an interesting atmosphere for the learners to improve their listening comprehension while benefiting from peer interaction and teacher’s support in the listening classroom. Teachers’ perceptions were also realistic regarding using nursery rhymes in teaching listening, especially for young learners. As to the implication side, finding can contribute to the positive application of nursery rhymes in paving the way for young learners to improve their listening comprehension ability.

  18. A cross-language study of decontextualized vocabulary comprehension in toddlerhood and kindergarten readiness.

    Science.gov (United States)

    Friend, Margaret; Smolak, Erin; Liu, Yushuang; Poulin-Dubois, Diane; Zesiger, Pascal

    2018-04-05

    Recent studies demonstrate that emerging literacy depends on earlier language achievement. Importantly, most extant work focuses on parent-reported production prior to 30 months of age. Of interest is whether and how directly assessed vocabulary comprehension in the 2nd year of life supports vocabulary and kindergarten readiness in the 4th year. We first contrasted orthogonal indices of parent-reported production and directly assessed vocabulary comprehension and found that comprehension was a stronger predictor of child outcomes. We then assessed prediction from vocabulary comprehension controlling for maternal education, preschool attendance, and child sex. In 3 studies early, decontextualized vocabulary comprehension emerged as a significant predictor of 4th year language and kindergarten readiness accounting for unique variance above demographic control variables. Further we found that the effect of early vocabulary on 4th year kindergarten readiness was not mediated by 4th year vocabulary. This pattern of results emerged in English monolingual children (N = 48) and replicated in French monolingual (N = 58) and French-English bilingual children (N = 34). Our findings suggest that early, decontextualized vocabulary may provide a platform for the establishment of a conceptual system that supports both later vocabulary and kindergarten readiness, including the acquisition of a wide range of concepts including print and number. Differences between parent-reported and directly assessed vocabulary and the mechanisms by which decontextualized vocabulary may contribute to conceptual development are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  19. Applying Data-driven Imaging Biomarker in Mammography for Breast Cancer Screening: Preliminary Study

    OpenAIRE

    Kim, Eun-Kyung; Kim, Hyo-Eun; Han, Kyunghwa; Kang, Bong Joo; Sohn, Yu-Mee; Woo, Ok Hee; Lee, Chan Wha

    2018-01-01

    We assessed the feasibility of a data-driven imaging biomarker based on weakly supervised learning (DIB; an imaging biomarker derived from large-scale medical image data with deep learning technology) in mammography (DIB-MG). A total of 29,107 digital mammograms from five institutions (4,339 cancer cases and 24,768 normal cases) were included. After matching patients’ age, breast density, and equipment, 1,238 and 1,238 cases were chosen as validation and test sets, respectively, and the remai...

  20. Children´s exposure to environmental pollutants and biomarkers of genetic damage. II. Results of a comprehensive literature search and meta-analysis. search

    Czech Academy of Sciences Publication Activity Database

    Neri, M.; Ugolini, D.; Bonassi, S.; Fucic, A.; Holland, N.; Knudsen, L. E.; Šrám, Radim; Ceppi, M.; Bocchini, V.; Merlo, D.F.

    2006-01-01

    Roč. 612, - (2006), s. 14-39 ISSN 1383-5742 Institutional research plan: CEZ:AV0Z50390512 Keywords : molecular epidemiological studies * children * environmental pollution Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 7.579, year: 2006

  1. Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study.

    Science.gov (United States)

    Ding, Hongliu; Dhima, Kaltra; Lockhart, Kaitlin C; Locascio, Joseph J; Hoesing, Ashley N; Duong, Karen; Trisini-Lipsanopoulos, Ana; Hayes, Michael T; Sohur, U Shivraj; Wills, Anne-Marie; Mollenhauer, Brit; Flaherty, Alice W; Hung, Albert Y; Mejia, Nicte; Khurana, Vikram; Gomperts, Stephen N; Selkoe, Dennis J; Schwarzschild, Michael A; Schlossmacher, Michael G; Hyman, Bradley T; Sudarsky, Lewis R; Growdon, John H; Scherzer, Clemens R

    2013-10-22

    To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D3, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD). We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D3 and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.6) and 283 control subjects free of neurologic disease nested in the Harvard Biomarker Study. Plasma levels of 25-hydroxy-vitamin D3 were associated with PD in both univariate and multivariate analyses with p values = 0.0034 and 0.047, respectively. Total 25-hydroxy-vitamin D levels, the traditional composite measure of endogenous and exogenous vitamin D, were deficient in 17.6% of patients with PD compared with 9.3% of controls. Low 25-hydroxy-vitamin D3 as well as total 25-hydroxy-vitamin D levels were correlated with higher total Unified Parkinson's Disease Rating Scale scores at baseline and during follow-up. Our study reveals an association between 25-hydroxy-vitamin D3 and PD and suggests that thousands of patients with PD in North America alone may be vitamin D-deficient. This finding has immediate relevance for individual patients at risk of falls as well as public health, and warrants further investigation into the mechanism underlying this association.

  2. The Biomarkers of Exposure and Effect in Agriculture (BEEA) Study: Rationale, Design, Methods, and Participant Characteristics.

    Science.gov (United States)

    Hofmann, Jonathan N; Beane Freeman, Laura E; Lynch, Charles F; Andreotti, Gabriella; Thomas, Kent W; Sandler, Dale P; Savage, Sharon A; Alavanja, Michael C

    2015-01-01

    Agricultural exposures including pesticides, endotoxin, and allergens have been associated with risk of various cancers and other chronic diseases, although the biological mechanisms underlying these associations are generally unclear. To facilitate future molecular epidemiologic investigations, in 2010 the study of Biomarkers of Exposure and Effect in Agriculture (BEEA) was initiated within the Agricultural Health Study, a large prospective cohort in Iowa and North Carolina. Here the design and methodology of BEEA are described and preliminary frequencies for participant characteristics and current agricultural exposures are reported. At least 1,600 male farmers over 50 years of age will be enrolled in the BEEA study. During a home visit, participants are asked to complete a detailed interview about recent agricultural exposures and provide samples of blood, urine, and (since 2013) house dust. As of mid-September 2014, in total, 1,233 participants have enrolled. Most of these participants (83%) were still farming at the time of interview. Among those still farming, the most commonly reported crops were corn (81%) and soybeans (74%), and the most frequently noted animals were beef cattle (35%) and hogs (13%). There were 861 (70%) participants who reported occupational pesticide use in the 12 months prior to interview; among these participants, the most frequently noted herbicides were glyphosate (83%) and 2,4-D (72%), and most commonly reported insecticides were malathion (21%), cyfluthrin (13%), and permethrin (12%). Molecular epidemiologic investigations within BEEA have the potential to yield important new insights into the biological mechanisms through which these or other agricultural exposures influence disease risk.

  3. Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and electrochemiluminescense-based multi-array platform

    NARCIS (Netherlands)

    Bussel, van B.C.T.; Ferreira, I.; Waarenburg, M.P.H.; Greevenbroek, van M.M.J.; Kallen, van der C.J.H.; Henry, R.M.A.; Feskens, E.J.M.; Stehouwer, C.D.A.; Schalkwijk, C.G.

    2013-01-01

    Background - In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. Methods - We measured, in a large ongoing cohort study (n = 574),

  4. Brain tissues atrophy is not always the best structural biomarker of physiological aging: A multimodal cross-sectional study.

    Science.gov (United States)

    Cherubini, Andrea; Caligiuri, Maria Eugenia; Péran, Patrice; Sabatini, Umberto; Cosentino, Carlo; Amato, Francesco

    2015-01-01

    This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2* relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. These findings highlight the importance of a combined evaluation of multimodal biomarkers for the study of aging and point to a number of novel applications for the method described.

  5. Data on serologic inflammatory biomarkers assessed using multiplex assays and host characteristics in the Multicenter AIDS Cohort Study (MACS

    Directory of Open Access Journals (Sweden)

    Heather S. McKay

    2016-12-01

    Full Text Available This article contains data on the associations between fixed and modifiable host characteristics and twenty-three biomarkers of inflammation and immune activation measured longitudinally in a cohort of 250 HIV-uninfected men from the Multicenter AIDS Cohort Study (1984–2009 after adjusting for age, study site, and blood draw time of day using generalized gamma regression. This article also presents associations between each biomarker and each host characteristic in a sample restricted to 2001–2009. These data are supplemental to our original research article entitled “Host factors associated with serologic inflammatory markers assessed using multiplex assays” (McKay, S. Heather, Bream, H. Jay, Margolick, B. Joseph, Martínez-Maza, Otoniel, Phair, P. John, Rinaldo, R. Charles, Abraham, G. Alison, L.P. Jacobson, 2016 [1].

  6. Characterization of neurophysiologic and neurocognitive biomarkers for use in genomic and clinical outcome studies of schizophrenia.

    Directory of Open Access Journals (Sweden)

    Gregory A Light

    Full Text Available Endophenotypes are quantitative, laboratory-based measures representing intermediate links in the pathways between genetic variation and the clinical expression of a disorder. Ideal endophenotypes exhibit deficits in patients, are stable over time and across shifts in psychopathology, and are suitable for repeat testing. Unfortunately, many leading candidate endophenotypes in schizophrenia have not been fully characterized simultaneously in large cohorts of patients and controls across these properties. The objectives of this study were to characterize the extent to which widely-used neurophysiological and neurocognitive endophenotypes are: 1 associated with schizophrenia, 2 stable over time, independent of state-related changes, and 3 free of potential practice/maturation or differential attrition effects in schizophrenia patients (SZ and nonpsychiatric comparison subjects (NCS. Stability of clinical and functional measures was also assessed.Participants (SZ n = 341; NCS n = 205 completed a battery of neurophysiological (MMN, P3a, P50 and N100 indices, PPI, startle habituation, antisaccade, neurocognitive (WRAT-3 Reading, LNS-forward, LNS-reorder, WCST-64, CVLT-II. In addition, patients were rated on clinical symptom severity as well as functional capacity and status measures (GAF, UPSA, SOF. 223 subjects (SZ n = 163; NCS n = 58 returned for retesting after 1 year.Most neurophysiological and neurocognitive measures exhibited medium-to-large deficits in schizophrenia, moderate-to-substantial stability across the retest interval, and were independent of fluctuations in clinical status. Clinical symptoms and functional measures also exhibited substantial stability. A Longitudinal Endophenotype Ranking System (LERS was created to rank neurophysiological and neurocognitive biomarkers according to their effect sizes across endophenotype criteria.The majority of neurophysiological and neurocognitive measures exhibited deficits in

  7. Characterization of neurophysiologic and neurocognitive biomarkers for use in genomic and clinical outcome studies of schizophrenia.

    Science.gov (United States)

    Light, Gregory A; Swerdlow, Neal R; Rissling, Anthony J; Radant, Allen; Sugar, Catherine A; Sprock, Joyce; Pela, Marlena; Geyer, Mark A; Braff, David L

    2012-01-01

    Endophenotypes are quantitative, laboratory-based measures representing intermediate links in the pathways between genetic variation and the clinical expression of a disorder. Ideal endophenotypes exhibit deficits in patients, are stable over time and across shifts in psychopathology, and are suitable for repeat testing. Unfortunately, many leading candidate endophenotypes in schizophrenia have not been fully characterized simultaneously in large cohorts of patients and controls across these properties. The objectives of this study were to characterize the extent to which widely-used neurophysiological and neurocognitive endophenotypes are: 1) associated with schizophrenia, 2) stable over time, independent of state-related changes, and 3) free of potential practice/maturation or differential attrition effects in schizophrenia patients (SZ) and nonpsychiatric comparison subjects (NCS). Stability of clinical and functional measures was also assessed. Participants (SZ n = 341; NCS n = 205) completed a battery of neurophysiological (MMN, P3a, P50 and N100 indices, PPI, startle habituation, antisaccade), neurocognitive (WRAT-3 Reading, LNS-forward, LNS-reorder, WCST-64, CVLT-II). In addition, patients were rated on clinical symptom severity as well as functional capacity and status measures (GAF, UPSA, SOF). 223 subjects (SZ n = 163; NCS n = 58) returned for retesting after 1 year. Most neurophysiological and neurocognitive measures exhibited medium-to-large deficits in schizophrenia, moderate-to-substantial stability across the retest interval, and were independent of fluctuations in clinical status. Clinical symptoms and functional measures also exhibited substantial stability. A Longitudinal Endophenotype Ranking System (LERS) was created to rank neurophysiological and neurocognitive biomarkers according to their effect sizes across endophenotype criteria. The majority of neurophysiological and neurocognitive measures exhibited deficits in patients

  8. Effects of Strategy Instruction in an EFL Reading Comprehension Course: A Case Study

    Directory of Open Access Journals (Sweden)

    Sergio Lopera Medina

    2012-01-01

    Full Text Available Strategy instruction is useful in teaching contexts. This paper examines the effects of strategy instruction in an EFL reading comprehension course carried out with 26 undergraduate students at a Colombian university. As a research method, a case study was implemented. There were three instruments with which to collect data: reading comprehension tests, teacher's field notes and self-reflection in class at the strategy instruction phase, and a learning perception questionnaire. Given that students improved in reading comprehension, it would seem that reading strategy instruction is indeed very useful. Also, it was noted that when students applied reading strategies, they became more self-confident and this in turn enhanced their motivation. Finally, when students applied the reading strategy approach, the use of dictionaries decreased considerably.

  9. A Study of the Application of Big Data in a Rural Comprehensive Information Service

    Directory of Open Access Journals (Sweden)

    Leifeng Guo

    2015-05-01

    Full Text Available Big data has attracted extensive interest due to its potential tremendous social and scientific value. Researchers are also trying to extract potential value from agriculture big data. This paper presents a study of information services based on big data from the perspective of a rural comprehensive information service. First, we introduce the background of the rural comprehensive information service, and then we present in detail the National Rural Comprehensive Information Service Platform (NRCISP, which is supported by the national science and technology support program. Next, we discuss big data in the NRCISP according to data characteristics, data sources, and data processing. Finally, we discuss a service model and services based on big data in the NRCISP.

  10. Comprehension of metaphors and idioms in patients with Alzheimer's disease: a longitudinal study.

    Science.gov (United States)

    Papagno, C

    2001-07-01

    Language in patients with Alzheimer's disease has been extensively studied, with the exception of non-literal language comprehension. However, in our speech, we often make use of expressions, which are not necessarily interpreted on a literal ground. Comprehension of metaphors and idioms was examined in 39 patients with probable early Alzheimer's disease. The results showed that the decline of figurative language is not an early symptom of dementia and can occur independently from the impairment of propositional language. It was also found that metaphors and idioms differ as far as the predominant kind of error is concerned.

  11. Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers

    DEFF Research Database (Denmark)

    Leitão, Maria João; Baldeiras, Inês; Herukka, Sanna-Kaisa

    2015-01-01

    INTRODUCTION: Core cerebrospinal fluid (CSF) biomarkers - Aβ42, Tau, and phosphorylated Tau (pTau) - have been recently incorporated in the revised criteria for Alzheimer's disease (AD). However, their widespread clinical application lacks standardization. Pre-analytical sample handling and storage...

  12. Long-interval intracortical inhibition as biomarker for epilepsy : a transcranial magnetic stimulation study

    NARCIS (Netherlands)

    Bauer, Prisca R.; de Goede, Annika A.; Stern, William M.; Pawley, Adam D.; Chowdhury, Fahmida A.; Helling, Robert M.; Bouet, Romain; Kalitzin, Stiliyan N.; Visser, Gerhard H.; Sisodiya, Sanjay M.; Rothwell, John C.; Richardson, Mark P.; van Putten, Michel J.A.M.; Sander, Josemir W.

    2018-01-01

    Cortical excitability, as measured by transcranial magnetic stimulation combined with electromyography, is a potential biomarker for the diagnosis and follow-up of epilepsy. We report on long-interval intracortical inhibition data measured in four different centres in healthy controls (n = 95),

  13. Neural circuit of verbal humor comprehension in schizophrenia - an fMRI study

    Directory of Open Access Journals (Sweden)

    Przemysław Adamczyk

    2017-01-01

    Full Text Available Individuals with schizophrenia exhibit problems with understanding the figurative meaning of language. This study evaluates neural correlates of diminished humor comprehension observed in schizophrenia. The study included chronic schizophrenia (SCH outpatients (n = 20, and sex, age and education level matched healthy controls (n = 20. The fMRI punchline based humor comprehension task consisted of 60 stories of which 20 had funny, 20 nonsensical and 20 neutral (not funny punchlines. After the punchlines were presented, the participants were asked to indicate whether the story was comprehensible and how funny it was. Three contrasts were analyzed in both groups reflecting stages of humor processing: abstract vs neutral stories - incongruity detection; funny vs abstract - incongruity resolution and elaboration; and funny vs neutral – complete humor processing. Additionally, parametric modulation analysis was performed using both subjective ratings separately. Between-group comparisons revealed that the SCH subjects had attenuated activation in the right posterior superior temporal gyrus (BA 41 in case of irresolvable incongruity processing of nonsensical puns; in the left dorsomedial middle and superior frontal gyri (BA 8/9 in case of incongruity resolution and elaboration processing of funny puns; and in the interhemispheric dorsal anterior cingulate cortex (BA 24 in case of complete processing of funny puns. Additionally, during comprehensibility ratings the SCH group showed a suppressed activity in the left dorsomedial middle and superior frontal gyri (BA 8/9 and revealed weaker activation during funniness ratings in the left dorsal anterior cingulate cortex (BA 24. Interestingly, these differences in the SCH group were accompanied behaviorally by a protraction of time in both types of rating responses and by indicating funny punchlines less comprehensible. Summarizing, our results indicate neural substrates of humor comprehension

  14. Neural circuit of verbal humor comprehension in schizophrenia - an fMRI study.

    Science.gov (United States)

    Adamczyk, Przemysław; Wyczesany, Miroslaw; Domagalik, Aleksandra; Daren, Artur; Cepuch, Kamil; Błądziński, Piotr; Cechnicki, Andrzej; Marek, Tadeusz

    2017-01-01

    Individuals with schizophrenia exhibit problems with understanding the figurative meaning of language. This study evaluates neural correlates of diminished humor comprehension observed in schizophrenia. The study included chronic schizophrenia (SCH) outpatients (n = 20), and sex, age and education level matched healthy controls (n = 20). The fMRI punchline based humor comprehension task consisted of 60 stories of which 20 had funny, 20 nonsensical and 20 neutral (not funny) punchlines. After the punchlines were presented, the participants were asked to indicate whether the story was comprehensible and how funny it was. Three contrasts were analyzed in both groups reflecting stages of humor processing: abstract vs neutral stories - incongruity detection; funny vs abstract - incongruity resolution and elaboration; and funny vs neutral - complete humor processing. Additionally, parametric modulation analysis was performed using both subjective ratings separately. Between-group comparisons revealed that the SCH subjects had attenuated activation in the right posterior superior temporal gyrus (BA 41) in case of irresolvable incongruity processing of nonsensical puns; in the left dorsomedial middle and superior frontal gyri (BA 8/9) in case of incongruity resolution and elaboration processing of funny puns; and in the interhemispheric dorsal anterior cingulate cortex (BA 24) in case of complete processing of funny puns. Additionally, during comprehensibility ratings the SCH group showed a suppressed activity in the left dorsomedial middle and superior frontal gyri (BA 8/9) and revealed weaker activation during funniness ratings in the left dorsal anterior cingulate cortex (BA 24). Interestingly, these differences in the SCH group were accompanied behaviorally by a protraction of time in both types of rating responses and by indicating funny punchlines less comprehensible. Summarizing, our results indicate neural substrates of humor comprehension processing

  15. Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers

    International Nuclear Information System (INIS)

    Matheis, Katja A.; Com, Emmanuelle; Gautier, Jean-Charles; Guerreiro, Nelson; Brandenburg, Arnd; Gmuender, Hans; Sposny, Alexandra; Hewitt, Philip; Amberg, Alexander; Boernsen, Olaf; Riefke, Bjoern; Hoffmann, Dana; Mally, Angela; Kalkuhl, Arno; Suter, Laura; Dieterle, Frank; Staedtler, Frank

    2011-01-01

    The European InnoMed-PredTox project was a collaborative effort between 15 pharmaceutical companies, 2 small and mid-sized enterprises, and 3 universities with the goal of delivering deeper insights into the molecular mechanisms of kidney and liver toxicity and to identify mechanism-linked diagnostic or prognostic safety biomarker candidates by combining conventional toxicological parameters with 'omics' data. Mechanistic toxicity studies with 16 different compounds, 2 dose levels, and 3 time points were performed in male Crl: WI(Han) rats. Three of the 16 investigated compounds, BI-3 (FP007SE), Gentamicin (FP009SF), and IMM125 (FP013NO), induced kidney proximal tubule damage (PTD). In addition to histopathology and clinical chemistry, transcriptomics microarray and proteomics 2D-DIGE analysis were performed. Data from the three PTD studies were combined for a cross-study and cross-omics meta-analysis of the target organ. The mechanistic interpretation of kidney PTD-associated deregulated transcripts revealed, in addition to previously described kidney damage transcript biomarkers such as KIM-1, CLU and TIMP-1, a number of additional deregulated pathways congruent with histopathology observations on a single animal basis, including a specific effect on the complement system. The identification of new, more specific biomarker candidates for PTD was most successful when transcriptomics data were used. Combining transcriptomics data with proteomics data added extra value.

  16. New biomarkers of coffee consumption identified by the non-targeted metabolomic profiling of cohort study subjects.

    Directory of Open Access Journals (Sweden)

    Joseph A Rothwell

    Full Text Available Coffee contains various bioactives implicated with human health and disease risk. To accurately assess the effects of overall consumption upon health and disease, individual intake must be measured in large epidemiological studies. Metabolomics has emerged as a powerful approach to discover biomarkers of intake for a large range of foods. Here we report the profiling of the urinary metabolome of cohort study subjects to search for new biomarkers of coffee intake. Using repeated 24-hour dietary records and a food frequency questionnaire, 20 high coffee consumers (183-540 mL/d and 19 low consumers were selected from the French SU.VI.MAX2 cohort. Morning spot urine samples from each subject were profiled by high-resolution mass spectrometry. Partial least-square discriminant analysis of multidimensional liquid chromatography-mass spectrometry data clearly distinguished high consumers from low via 132 significant (p-value<0.05 discriminating features. Ion clusters whose intensities were most elevated in the high consumers were annotated using online and in-house databases and their identities checked using commercial standards and MS-MS fragmentation. The best discriminants, and thus potential markers of coffee consumption, were the glucuronide of the diterpenoid atractyligenin, the diketopiperazine cyclo(isoleucyl-prolyl, and the alkaloid trigonelline. Some caffeine metabolites, such as 1-methylxanthine, were also among the discriminants, however caffeine may be consumed from other sources and its metabolism is subject to inter-individual variation. Receiver operating characteristics curve analysis showed that the biomarkers identified could be used effectively in combination for increased sensitivity and specificity. Once validated in other cohorts or intervention studies, these specific single or combined biomarkers will become a valuable alternative to assessment of coffee intake by dietary survey and finally lead to a better understanding of

  17. A pilot randomized study of a gratitude journaling intervention on HRV and inflammatory biomarkers in Stage B heart failure patients

    Science.gov (United States)

    Redwine, Laura; Henry, Brook L.; Pung, Meredith A.; Wilson, Kathleen; Chinh, Kelly; Knight, Brian; Jain, Shamini; Rutledge, Thomas; Greenberg, Barry; Maisel, Alan; Mills, Paul J

    2016-01-01

    Objective Stage B, asymptomatic heart failure (HF) presents a therapeutic window for attenuating disease progression and development of HF symptoms, and improving quality of life. Gratitude, the practice of appreciating positive life features, is highly related to quality of life, leading to development of promising clinical interventions. However, few gratitude studies have investigated objective measures of physical health; most relied on self-report measures. We conducted a pilot study in Stage B HF patients to examine whether gratitude journaling improved biomarkers related to HF prognosis. Methods Patients (N = 70; mean age = 66.2 years, SD = 7.6) were randomized to an 8-week gratitude journaling intervention or treatment as usual (TAU). Baseline (T1) assessments included 6-item Gratitude Questionnaire (GQ-6), resting heart rate variability (HRV), and an inflammatory biomarker index. At T2 (mid-intervention) GQ6 was measured. At T3 (post-intervention), T1 measures were repeated but also included a gratitude journaling task. Results The gratitude intervention was associated with improved trait gratitude scores (F = 6.0, p = .017, η2 = .10), reduced inflammatory biomarker index score over time (F = 9.7, p = .004, η2 = .21) and increased parasympathetic HRV responses during the gratitude journaling task (F = 4.2, p = .036, η2 = .15), compared with TAU. However, there were no resting pre- to post-intervention group differences in HRV (p's > .10). Conclusions Gratitude journaling may improve biomarkers related to HF morbidity, such as reduced inflammation; large-scale studies with active control conditions are needed to confirm these findings. PMID:27187845

  18. Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

    Science.gov (United States)

    Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

    2017-01-01

    In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy. PMID:28968445

  19. The 3R study strategy to improve text retention and text comprehension

    NARCIS (Netherlands)

    Reijners, Pauline; Kester, Liesbeth; Wetzels, Sandra; Kirschner, Paul A.

    2013-01-01

    Reijners, P. B. G., Kester, L., Wetzels, S. A. J., & Kirschner, P. A. (2013, 27 August). The 3R study strategy to improve text retention and text comprehension. In B. Klein (Chair), Effective Learning Strategies and their Usage in Self-regulated Training Programs and Computer-Based Learning.

  20. A Cross-Sectional Study of Fluency and Reading Comprehension in Spanish Primary School Children

    Science.gov (United States)

    Calet, Nuria; Gutiérrez-Palma, Nicolás; Defior, Sylvia

    2015-01-01

    The importance of prosodic elements is recognised in most definitions of fluency. Although speed and accuracy have been typically considered the constituents of reading fluency, prosody is emerging as an additional component. The relevance of prosody in comprehension is increasingly recognised in the latest studies. The purpose of this research is…

  1. Evidence for bilateral involvement in idiom comprehension : An fMRI study

    NARCIS (Netherlands)

    Zempleni, Monika-Zita; Haverkort, Marco; Renken, Remco; Stowe, Laurie A.

    2007-01-01

    The goal of the current study was to identify the neural substrate of idiom comprehension using fMRI. Idioms are familiar, fixed expressions whose meaning is not dependent on the literal interpretation of the component words. We presented literally plausible idioms in a sentence forcing a figurative

  2. The Effects of Using Advance Organizers on Improving EFL Learners' Listening Comprehension: A Mixed Method Study

    Science.gov (United States)

    Jafari, Khadijeh; Hashim, Fatimah

    2012-01-01

    This study investigated the effects of using two types of written advance organizers, key sentences and key vocabulary, on the improvement of EFL learners' listening comprehension. 108 second year university students at the higher and lower listening proficiency levels were randomly assigned to one control group and two experimental groups. Prior…

  3. Metaphor Comprehension in Autistic Spectrum Disorders: Case Studies of Two High-Functioning Children

    Science.gov (United States)

    Melogno, Sergio; D'Ardia, Caterina; Pinto, Maria Antonietta; Levi, Gabriel

    2012-01-01

    This article presents case studies on metaphor comprehension in two boys with high-functioning autistic spectrum disorder, aged 9;1 (9 years, 1 month) and 8;11. The participants were assessed twice, before and after an intervention program aimed at improving their social skills. The focus of the article is on the specific patterns exhibited by…

  4. Case Study of an Institutionalized Urban Comprehensive School Physical Activity Program

    Science.gov (United States)

    Doolittle, Sarah A.; Rukavina, Paul B.

    2014-01-01

    This single case study (Yin, 2009) compares an established urban physical education/ sport/physical activity program with two models: Comprehensive School Physical Activity Program/CSPAP (AAHPERD, 2013; CDC, 2013); and Lawson's propositions (2005) for sport, exercise and physical education for empowerment and community development to determine…

  5. The Effects of CLIL on Oral Comprehension and Production: A Longitudinal Case Study

    Science.gov (United States)

    Pérez Cañado, María Luisa; Lancaster, Nina Karen

    2017-01-01

    This article reports on the outcomes of a longitudinal case study to gauge the impact of content and language integrated learning (CLIL) on two of the least researched language skills: oral comprehension and production. It worked with 24 students in the fourth grade of Compulsory Secondary Education in a public school in Andalusia (southern Spain)…

  6. A Study of Reading Comprehension in Older Children Using Selected Korean Bible Translations

    Science.gov (United States)

    Kim, Jae Woo

    2014-01-01

    Problem: The problem of this study was to determine the difference in Bible comprehension scores among gender-based groups of older children using selected passages from three Bible translations: the Children's Bible, the Easy Bible, and the New Revised Korean Bible. Procedures: A total of 288 older children in three churches (Beautiful Baptist…

  7. Comprehensive Environmental Assessment and U.S. EPA Nanomaterial Case Studies

    Science.gov (United States)

    These case studies are not completed risk assessments but are structured around an approach known as comprehensive environmental assessment (CEA), which combines a product life cycle framework with the risk assessment paradigm (Davis, J.M., J. Nanosci. Nanotech. 7:402-9, 2007). ...

  8. A Comprehensive HIV Stigma-reduction and Wellness-enhancement Community Intervention: A Case Study.

    NARCIS (Netherlands)

    French, H.; Greeff, M.; Watson, M.J.; Doak, C.M.

    2014-01-01

    We describe the implementation of a comprehensive HIV stigma-reduction and wellness-enhancement community intervention that focused on people living with HIV (PLWH), as well as people living close to them (PLC) from six designated groups. A holistic multiple case study design was used in urban and

  9. Comprehensive Adult Student Assessment Systems Braille Reading Assessment: An Exploratory Study

    Science.gov (United States)

    Posey, Virginia K.; Henderson, Barbara W.

    2012-01-01

    Introduction: This exploratory study determined whether transcribing selected test items on an adult life and work skills reading test into braille could maintain the same approximate scale-score range and maintain fitness within the item response theory model as used by the Comprehensive Adult Student Assessment Systems (CASAS) for developing…

  10. Deaf Education Teacher Preparation: A Phenomenological Case Study of a Graduate Program with a Comprehensive Philosophy

    Science.gov (United States)

    Engler, Karen S.; MacGregor, Cynthia J.

    2018-01-01

    At a time when deaf education teacher preparation programs are declining in number, little is known about their actual effectiveness. A phenomenological case study of a graduate-level comprehensive deaf education teacher preparation program at a midwestern university explored empowered and enabled learning of teacher candidates using the Missouri…

  11. Supporting nanomaterial risk assessment by case studies of nano-titanium dioxide using comprehensive environmental assessment

    Science.gov (United States)

    Here we describe a comprehensive environmental assessment (CEA) approach for two case studies of nano-titanium dioxide (nano-TiO2) in real world applications: water treatment and sunscreen. CEA combines a product life cycle framework with the risk assessment paradigm.

  12. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R

    2016-01-01

    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...

  13. Correlates of lower comprehension of informed consent among participants enrolled in a cohort study in Pune, India.

    Science.gov (United States)

    Joglekar, Neelam S; Deshpande, Swapna S; Sahay, Seema; Ghate, Manisha V; Bollinger, Robert C; Mehendale, Sanjay M

    2013-03-01

    Optimum comprehension of informed consent by research participants is essential yet challenging. This study explored correlates of lower comprehension of informed consent among 1334 participants of a cohort study aimed at estimating HIV incidence in Pune, India. As part of the informed consent process, a structured comprehension tool was administered to study participants. Participants scoring ≥90% were categorised into the 'optimal comprehension group', whilst those scoring 80-89% were categorised into the 'lower comprehension group'. Data were analysed to identify sociodemographic and behavioural correlates of lower consent comprehension. The mean ± SD comprehension score was 94.4 ± 5.00%. Information pertaining to study-related risks was not comprehended by 61.7% of participants. HIV-negative men (adjusted OR [AOR] = 4.36, 95% CI 1.71-11.05) or HIV-negative women (AOR = 13.54, 95% CI 6.42-28.55), illiteracy (AOR= 1.65, 95% CI 1.19-2.30), those with a history of multiple partners (AOR = 1.73, 95% CI 1.12-2.66) and those never using condoms (AOR = 1.35, 95% CI 1.01-1.82) were more likely to have lower consent comprehension. We recommend exploration of domains of lower consent comprehension using a validated consent comprehension tool. Improved education in these specific domains would optimise consent comprehension among research participants.

  14. Applications of biological tools or biomarkers in aquatic biota: A case study of the Tamar estuary, South West England.

    Science.gov (United States)

    Dallas, Lorna J; Jha, Awadhesh N

    2015-06-30

    Biological systems are the ultimate recipients of pollutant-induced damage. Consequently, our traditional reliance on analytical tools is not enough to assess ecosystem health. Biological responses or biomarkers are therefore also considered to be important tools for environmental hazard and risk assessments. Due to historical mining, other anthropogenic activities, and its conservational importance (e.g. NATURA sites, SACs), the Tamar estuary in South West England is an ideal environment in which to examine applications of such biological tools. This review presents a thorough and critical evaluation of the different biological tools used in the Tamar estuary thus far, while also discussing future perspectives for biomarker studies from a global perspective. In particular, we focus on the challenges which hinder applications of biological tools from being more readily incorporated into regulatory frameworks, with the aim of enabling both policymakers and primary stakeholders to maximise the environmental relevance and regulatory usefulness of such tools. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study.

    Science.gov (United States)

    Sayanthooran, Saravanabavan; Magana-Arachchi, Dhammika N; Gunerathne, Lishanthe; Abeysekera, Tilak

    2017-01-19

    In Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu). Identification of novel biomarkers that are customized to the specific causative factors would lead to early diagnosis and clearer prognosis of the diseases. This study aimed to find genetic biomarkers in blood to distinguish and identify CKDu from CKD as well as healthy populations from CKDu endemic and non-endemic areas of Sri Lanka. The expression patterns of a selected panel of 12 potential genetic biomarkers were analyzed in blood using RT-qPCR. Fold changes of gene expressions in early and late stages of CKD and CKDu patients, and an apparently healthy population of a CKDu endemic area, Girandurukotte (GH) were calculated relative to apparently healthy volunteers from a CKDu non-endemic area, Kandy (KH) of Sri Lanka, using the comparative CT method. Significant differences were observed between KH and early stage CKDu for both the insulin-like growth factor binding protein 1 (IGFBP1; p = 0.012) and kidney injury molecule-1 (KIM1; p = 0.003) genes, and KH and late stage CKD and CKDu for the glutathione-S-transferase mu 1 (GSTM1; p CKDu (p CKDu, whereas these genes in addition with FN1, IGFBP3 and KLK1 could be used to monitor progression of CKDu. The regulation of these genes has to be studied on larger populations to validate their efficiency for further clinical use.

  16. A pilot study to evaluate the application of a generic protein standard panel for quality control of biomarker detection technologies

    Directory of Open Access Journals (Sweden)

    Valdivia Hernan J

    2011-08-01

    Full Text Available Abstract Background Protein biomarker studies are currently hampered by a lack of measurement standards to demonstrate quality, reliability and comparability across multiple assay platforms. This is especially pertinent for immunoassays where multiple formats for detecting target analytes are commonly used. Findings In this pilot study a generic panel of six non-human protein standards (50 - 10^7 pg/mL of varying abundance was prepared as a quality control (QC material. Simulated "normal" and "diseased" panels of proteins were prepared in pooled human plasma and incorporated into immunoassays using the Meso Scale Discovery® (MSD® platform to illustrate reliable detection of the component proteins. The protein panel was also evaluated as a spike-in material for a model immunoassay involving detection of ovarian cancer biomarkers within individual human plasma samples. Our selected platform could discriminate between two panels of the proteins exhibiting small differences in abundance. Across distinct experiments, all component proteins exhibited reproducible signal outputs in pooled human plasma. When individual donor samples were used, half the proteins produced signals independent of matrix effects. These proteins may serve as a generic indicator of platform reliability. Each of the remaining proteins exhibit differential signals across the distinct samples, indicative of sample matrix effects, with the three proteins following the same trend. This subset of proteins may be useful for characterising the degree of matrix effects associated with the sample which may impact on the reliability of quantifying target diagnostic biomarkers. Conclusions We have demonstrated the potential utility of this panel of standards to act as a generic QC tool for evaluating the reproducibility of the platform for protein biomarker detection independent of serum matrix effects.

  17. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

    DEFF Research Database (Denmark)

    Hagmar, L; Bonassi, S; Strömberg, U

    1998-01-01

    cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each...... as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed...... country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers...

  18. A study of the international trend and comprehensive enhancement program on the Nuclear Power Plant safety

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Soon Hong; Cho, Nam Jin; Paek, Won Phil [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1990-12-15

    The objectives of this study are as follows : overview of the international trend related to the safety of Nuclear Power Plant(NPPs), study of the present status of NPP safety in Korea in aspects of design, construction and operation, suggestion of the comprehensive program to improve NPP safety in Korea. The results of this study can contribute to improve the safety of existing and future NPPs, and to establish the severe accident policy in Korea.

  19. A study of the international trend and comprehensive enhancement program on the Nuclear Power Plant safety

    International Nuclear Information System (INIS)

    Jang, Soon Hong; Cho, Nam Jin; Paek, Won Phil

    1990-12-01

    The objectives of this study are as follows : overview of the international trend related to the safety of Nuclear Power Plant(NPPs), study of the present status of NPP safety in Korea in aspects of design, construction and operation, suggestion of the comprehensive program to improve NPP safety in Korea. The results of this study can contribute to improve the safety of existing and future NPPs, and to establish the severe accident policy in Korea

  20. Vitamins and iron blood biomarkers are associated with blood pressure levels in European adolescents. The HELENA study.

    Science.gov (United States)

    de Moraes, Augusto César Ferreira; Gracia-Marco, Luis; Iglesia, Iris; González-Gross, Marcela; Breidenassel, Christina; Ferrari, Marika; Molnar, Dénes; Gómez-Martínez, Sonia; Androutsos, Odysseas; Kafatos, Anthony; Cuenca-García, Magdalena; Sjöström, Michael; Gottrand, Frederic; Widhalm, Kurt; Carvalho, Heráclito Barbosa; Moreno, Luis A

    2014-01-01

    Previous research showed that low concentration of biomarkers in the blood during adolescence (i.e., iron status; retinol; and vitamins B6, B12, C, and D) may be involved in the early stages of development of many chronic diseases, such as hypertension. The aim was to evaluate if iron biomarkers and vitamins in the blood are associated with blood pressure in European adolescents. Participants from the Healthy Lifestyle in Europe by Nutrition in Adolescence cross-sectional study (N = 1089; 12.5-17.5 y; 580 girls) were selected by complex sampling. Multilevel linear regression models examined the associations between iron biomarkers and vitamins in the blood and blood pressure; the analyses were stratified by sex and adjusted for contextual and individual potential confounders. A positive association was found in girls between RBC folate concentration and systolic blood pressure (SBP) (β = 3.19; 95% confidence interval [CI], 0.61-5.77), although no association between the vitamin serum biomarkers concentrations and diastolic blood pressure (DBP) was found. In boys, retinol was positively associated with DBP (β = 3.84; 95% CI, 0.51-7.17) and vitamin B6 was positively associated with SBP (β = 3.82; 95% CI, 1.46-6.18). In contrast, holotranscobalamin was inversely associated with SBP (β = -3.74; 95% CI, -7.28 to -0.21). Levels of RBC folate and vitamin B6 in blood may affect BP in adolescents. In this context, programs aimed at avoiding high BP levels should promote healthy eating behavior by focusing on the promotion of vegetable proteins and foods rich in vitamin B12 (i.e., white meat and eggs), which may help to achieve BP blood control in adolescents. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Intercorrelation between immunological biomarkers and job stress indicators among female nurses: A nine-month longitudinal study

    Directory of Open Access Journals (Sweden)

    Hyung-Suk eYoon

    2014-10-01

    Full Text Available Some immunological biomarkers have been reported to be associated with job stress. This study was conducted to explore an intercorrelation between the psychological components of job stress and various immunological biomarkers among female nurses. To assess monthly and weekly job stress, 41 nurses had repeatedly completed the questionnaires such as the GJSQ, the POMS and the CES-D. Using flow cytometry and radioimmunoassay, the number of white blood cells, lymphocytic proliferation to mitogens, and toxoid were measured. Moreover, the levels of hydrocortisol, IL-b, INF-r, and TNF-a and salivary IgA were eveluated by enzyme-linked immunosorbent assay. When the Pearson correlation coefficients between job stress and immunological biomarkers were estimated after adjusting for age and smoking status, Clashes: conflict at work was significantly related to the number of CD4 cells (r = 0.36, p-value < 0.05, CD4 to CD8 ratio (0.35; < 0.05, response to concanavalin A (0.42; < 0.05, and phytohemagglutinin (0.35; < 0.05. Additionally, the level of hydrocortisol was significantly related to seven psychosocial measures; i.e., role conflict (-0.47; < 0.01, role ambiguity (-0.39; < 0.05, clashes at work (-0.38; < 0.05, control & influence at work (0.53; < 0.01, task control (0.55; < 0.001, resources at work (0.35; < 0.05, and skill underutilization (0.43; < 0.05. The results indicate that 1 the psychological job stress is associated with the levels of some immunological biomarkers in nurses; and 2 especially, hydrocortisol shows a remarkable relationship with diverse job stress indicators.

  2. The Effect of the Cherry Hill Study Skills Program on Eighth Grade Students' Reading Comprehension and Study Skills.

    Science.gov (United States)

    La Marca, Marilyn Tierney

    A study was conducted to determine the effects of the "Cherry Hill Study Skills Program" on eighth grade students' reading comprehension and study skills. The "Cherry Hill Study Skills Program" is a process oriented course dealing with the sequential development of nine specific skills deemed essential to the retrieval and retention of information…

  3. Linking stress and immunity: Immunoglobulin A as a non-invasive physiological biomarker in animal welfare studies.

    Science.gov (United States)

    Staley, Molly; Conners, Melinda G; Hall, Katie; Miller, Lance J

    2018-04-26

    As the animal welfare community strives to empirically assess how care and management practices can help maintain or even enhance welfare, the development of tools for non-invasively measuring physiological biomarkers is essential. Of the suite of physiological biomarkers, Immunoglobulin A (IgA), particularly the secretory form (Secretory IgA or SIgA), is at the forefront because of its crucial role in mucosal immunity and links to physical health, stress, and overall psychological well-being. While interpretation of SIgA values on short time scales is complex, long-term SIgA patterns are consistent: conditions that create chronic stress lead to suppression of SIgA. In contrast, when welfare is enhanced, SIgA concentrations are predicted to stabilize at higher concentrations. In this review, we examine how SIgA concentrations are reflective of both physiological stress and immune function. We then review the literature associating SIgA concentrations with various metrics of animal welfare and provide detailed methodological considerations for SIgA monitoring. Overall, our aim is to provide an in-depth discussion regarding the value of SIgA as physiological biomarker to studies aiming to understand the links between stress and immunity. Copyright © 2017. Published by Elsevier Inc.

  4. The Comprehension of Familiar and Novel Metaphoric Meanings in Schizophrenia: A Pilot Study

    Science.gov (United States)

    Rapp, Alexander M.; Felsenheimer, Anne K.; Langohr, Karin; Klupp, Magdalena

    2018-01-01

    Miscomprehension of nonliteral (“figurative”) language like metaphors, proverbs, idioms, and ironic expressions by patients with schizophrenia is a phenomenon mentioned already in historical psychiatric descriptions. However, it was only recently that studies did differentiate between novel and conventional metaphors, a factor that is known to influence the difficulty of comprehension in healthy subjects. Further, familiarity with stimuli is an important factor for comprehension, which was not recommended in utmost previous studies. In this study, 23 patients with DSM IV schizophrenia and 19 healthy control subjects performed a newly-developed German metaphor comprehension test with three types of stimuli: novel metaphors, conventional German metaphors, and meaningless statements. During the test procedure, participants indicated familiarity with the stimulus and then matched the meaning with one out of four given alternatives. Familiarity rankings did not significantly differ between patients and control subjects. However, on descriptive level, there was a tendency for healthy controls to be more familiar with conventional metaphors than schizophrenic patients. Further, comprehension of conventional and novel metaphors differed significantly between the groups, with higher performance in healthy controls. Considering only those metaphors that had been ranked as familiar, patients only revealed significant lower performance opposed to controls regarding novel metaphors, while they did not differ in conventional metaphors. Taken together, the results indicate that patients with schizophrenia might show an altered way of comprehension in novel metaphors, leading to more misunderstandings. However, their previously reported impairments in conventional metaphors might rather be due to a lack of familiarity with the stimuli—making conventional metaphors to novel metaphors in the individual case. PMID:29354082

  5. The Comprehension of Familiar and Novel Metaphoric Meanings in Schizophrenia: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Alexander M. Rapp

    2018-01-01

    Full Text Available Miscomprehension of nonliteral (“figurative” language like metaphors, proverbs, idioms, and ironic expressions by patients with schizophrenia is a phenomenon mentioned already in historical psychiatric descriptions. However, it was only recently that studies did differentiate between novel and conventional metaphors, a factor that is known to influence the difficulty of comprehension in healthy subjects. Further, familiarity with stimuli is an important factor for comprehension, which was not recommended in utmost previous studies. In this study, 23 patients with DSM IV schizophrenia and 19 healthy control subjects performed a newly-developed German metaphor comprehension test with three types of stimuli: novel metaphors, conventional German metaphors, and meaningless statements. During the test procedure, participants indicated familiarity with the stimulus and then matched the meaning with one out of four given alternatives. Familiarity rankings did not significantly differ between patients and control subjects. However, on descriptive level, there was a tendency for healthy controls to be more familiar with conventional metaphors than schizophrenic patients. Further, comprehension of conventional and novel metaphors differed significantly between the groups, with higher performance in healthy controls. Considering only those metaphors that had been ranked as familiar, patients only revealed significant lower performance opposed to controls regarding novel metaphors, while they did not differ in conventional metaphors. Taken together, the results indicate that patients with schizophrenia might show an altered way of comprehension in novel metaphors, leading to more misunderstandings. However, their previously reported impairments in conventional metaphors might rather be due to a lack of familiarity with the stimuli—making conventional metaphors to novel metaphors in the individual case.

  6. Biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected patients in the SMART study

    DEFF Research Database (Denmark)

    Peters, Lars; Neuhaus, Jacqueline; Duprez, Daniel

    2014-01-01

    BACKGROUND: Previous results from the SMART study showed that HIV/viral hepatitis co-infected persons with impaired liver function are at increased risk of death following interruption of antiretroviral therapy (ART). OBJECTIVES: To investigate the influence of fibrosis and ART interruption...... on levels of biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected persons in the SMART study. STUDY DESIGN: All HIV/HCV co-infected persons with stored plasma at study entry and at six months of follow-up were included (N=362). D-dimer, IL-6, sCD14 and hepatic...

  7. Plasma Soluble Prion Protein, a Potential Biomarker for Sport-Related Concussions: A Pilot Study

    OpenAIRE

    Pham, Nam; Akonasu, Hungbo; Shishkin, Rhonda; Taghibiglou, Changiz

    2015-01-01

    Sport-related mild traumatic brain injury (mTBI) or concussion is a significant health concern to athletes with potential long-term consequences. The diagnosis of sport concussion and return to sport decision making is one of the greatest challenges facing health care clinicians working in sports. Blood biomarkers have recently demonstrated their potential in assisting the detection of brain injury particularly, in those cases with no obvious physical injury. We have recently discovered plasm...

  8. Urinary Proteomics Pilot Study for Biomarker Discovery and Diagnosis in Heart Failure with Reduced Ejection Fraction.

    Directory of Open Access Journals (Sweden)

    Kasper Rossing

    Full Text Available Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF.Urine samples were analyzed by on-line capillary electrophoresis coupled to electrospray ionization micro time-of-flight mass spectrometry (CE-MS to generate individual urinary proteome profiles. In an initial biomarker discovery cohort, analysis of urinary proteome profiles from 33 HFrEF patients and 29 age- and sex-matched individuals without HFrEF resulted in identification of 103 peptides that were significantly differentially excreted in HFrEF. These 103 peptides were used to establish the support vector machine-based HFrEF classifier HFrEF103. In a subsequent validation cohort, HFrEF103 very accurately (area under the curve, AUC = 0.972 discriminated between HFrEF patients (N = 94, sensitivity = 93.6% and control individuals with and without impaired renal function and hypertension (N = 552, specificity = 92.9%. Interestingly, HFrEF103 showed low sensitivity (12.6% in individuals with diastolic left ventricular dysfunction (N = 176. The HFrEF-related peptide biomarkers mainly included fragments of fibrillar type I and III collagen but also, e.g., of fibrinogen beta and alpha-1-antitrypsin.CE-MS based urine proteome analysis served as a sensitive tool to determine a vast array of HFrEF-related urinary peptide biomarkers which might help improving our understanding and diagnosis of heart failure.

  9. Narrative comprehension and production in children with SLI: An eye movement study

    Science.gov (United States)

    ANDREU, LLORENÇ; SANZ-TORRENT, MONICA; OLMOS, JOAN GUÀRDIA; MACWHINNEY, BRIAN

    2014-01-01

    This study investigates narrative comprehension and production in children with specific language impairment (SLI). Twelve children with SLI (mean age 5; 8 years) and 12 typically developing children (mean age 5; 6 years) participated in an eye-tracking experiment designed to investigate online narrative comprehension and production in Catalan- and Spanish-speaking children with SLI. The comprehension task involved the recording of eye movements during the visual exploration of successive scenes in a story, while listening to the associated narrative. With regard to production, the children were asked to retell the story, while once again looking at the scenes, as their eye movements were monitored. During narrative production, children with SLI look at the most semantically relevant areas of the scenes fewer times than their age-matched controls, but no differences were found in narrative comprehension. Moreover, the analyses of speech productions revealed that children with SLI retained less information and made more semantic and syntactic errors during retelling. Implications for theories that characterize SLI are discussed. PMID:21453036

  10. An Exploratory Study of Reading Comprehension in College Students After Acquired Brain Injury.

    Science.gov (United States)

    Sohlberg, McKay Moore; Griffiths, Gina G; Fickas, Stephen

    2015-08-01

    This exploratory study builds on the small body of existing research investigating reading comprehension deficits in college students with acquired brain injury (ABI). Twenty-four community college students with ABI completed a battery of questionnaires and standardized tests to characterize self-perceptions of academic reading ability, performance on a standardized reading comprehension measure, and a variety of cognitive functions of this population. Half of the participants in the sample reported traumatic brain injury (n = 12) and half reported nontraumatic ABI (n = 12). College students with both traumatic and nontraumatic ABI cite problems with reading comprehension and academic performance postinjury. Mean performance on a standardized reading measure, the Nelson-Denny Reading Test (Brown, Fischo, & Hanna, 1993), was low to below average and was significantly correlated with performance on the Speed and Capacity of Language Processing Test (Baddeley, Emslie, & Nimmo-Smith, 1992). Injury status of traumatic versus nontraumatic ABI did not differentiate results. Regression analysis showed that measures of verbal attention and suppression obtained from the California Verbal Language Test-II (Delis, Kramer, Kaplan, & Ober, 2000) predicted total scores on the Nelson-Denny Reading Test. College students with ABI are vulnerable to reading comprehension problems. Results align with other research suggesting that verbal attention and suppression problems may be contributing factors.

  11. A Study on improvement of comprehensive environmental management system - activation of liberalized environmental management

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hweu Sung; Kang, Chul Goo [Korea Environment Institute, Seoul (Korea)

    1998-12-01

    As a part of improvement on a comprehensive environmental management system, this study was attempted to find an activating policy for a liberalized environmental management. This study provided an activation plan of reasonable environmental regulation reform and liberalized environmental management through the analysis of foreign examples and domestic situation. Furthermore, it analyzed an institutional mechanism for a smooth operation of liberalized environmental management. 68 refs., 5 figs., 51 tabs.

  12. A multiplex quantitative proteomics strategy for protein biomarker studies in urinary exosomes.

    Science.gov (United States)

    Raj, Delfin A A; Fiume, Immacolata; Capasso, Giovambattista; Pocsfalvi, Gabriella

    2012-06-01

    Urinary exosomes have received considerable attention as a potential biomarker source for the diagnosis of renal diseases. Notwithstanding, their use in protein biomarker research is hampered by the lack of efficient methods for vesicle isolation, lysis, and protein quantification. Here we report an improved ultracentrifugation-based method that facilitates the solubilization and removal of major impurities associated with urinary exosomes. A double-cushion sucrose/D(2)O centrifugation step was used after a two-step differential centrifugation to separate exosomes from the heavier vesicles. After the removal of uromodulin, 378 and 79 unique proteins were identified, respectively, in low- and high-density fractions. Comparison of our data with two previously published data sets helped to define proteins commonly found in urinary exosomes. Lysis, protein extraction, and in-solution digestion of exosomes were then optimized for MudPIT application. More than a hundred exosomal proteins were quantified by four-plex iTRAQ analysis of single and pooled samples from two different age groups. For healthy men, six proteins (TSN1, PODXL, IDHC, PPAP, ACBP, and ANXA5) showed significant expression differences between exosome pools of those aged 25-50 and 50-70 years old. Thus, exosomes isolated by our method provide the basis for the development of robust quantitative methods for protein biomarker research.

  13. Paleoenvironmental assessment of recent environmental changes in Florida Bay, USA: a biomarker based study

    Science.gov (United States)

    Xu, Y.; Holmes, C.W.; Jaffe, R.

    2007-01-01

    The extractable lipid compositions in four Florida Bay cores were determined in order to understand environmental changes over the last 160 years. The most significant environmental change was recorded by oscillations in the amplitude and frequency of biomarkers during the 20th century. Two seagrass molecular proxies (Paq and the C25/C27n-alkan-2-one ratio) reached a maximum post 1900, suggesting that abundant seagrass communities existed during the 20th century. A sharp drop in the Paq value from 0.65 to 0.48 in the central Bay at about 1987 seems to reflect seagrass die-off. The concentrations of microbial biomarkers (C20 HBIs, C25 HBIs and dinosterol) substantially increased after 1950 in the TC, BA and NB cores, reflecting an increase in algal (planktonic organism) primary productivity. However, the RB core presented the highest abundance of C25 HBIs and dinosterol during the period of 1880–1940, suggesting historically large inputs from diatoms and dinoflagellates. A substantial rise in abundance of taraxerol (a specific biomarker of mangroves) from 20 μg/g TOC in the 1830s to 279 μg/g TOC in the l980s is likely a result of increased mangrove primary productivity along the shore of the NE Bay. These changes are most likely the result of hydrological alterations in South Florida.

  14. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  15. Quantitative redox imaging biomarkers for studying tissue metabolic state and its heterogeneity

    Directory of Open Access Journals (Sweden)

    He N. Xu

    2014-03-01

    Full Text Available NAD+/NADH redox state has been implicated in many diseases such as cancer and diabetes as well as in the regulation of embryonic development and aging. To fluorimetrically assess the mitochondrial redox state, Dr. Chance and co-workers measured the fluorescence of NADH and oxidized flavoproteins (Fp including flavin–adenine–dinucleotide (FAD and demonstrated their ratio (i.e. the redox ratio is a sensitive indicator of the mitochondrial redox states. The Chance redox scanner was built to simultaneously measure NADH and Fp in tissue at submillimeter scale in 3D using the freeze-trap protocol. This paper summarizes our recent research experience, development and new applications of the redox scanning technique in collaboration with Dr. Chance beginning in 2005. Dr. Chance initiated or actively involved in many of the projects during the last several years of his life. We advanced the redox scanning technique by measuring the nominal concentrations (in reference to the frozen solution standards of the endogenous fluorescent analytes, i.e., [NADH] and [Fp] to quantify the redox ratios in various biological tissues. The advancement has enabled us to identify an array of the redox indices as quantitative imaging biomarkers (including [NADH], [Fp], [Fp]/([NADH]+[Fp], [NADH]/[Fp], and their standard deviations for studying some important biological questions on cancer and normal tissue metabolism. We found that the redox indices were associated or changed with (1 tumorigenesis (cancer versus non-cancer of human breast tissue biopsies; (2 tumor metastatic potential; (3 tumor glucose uptake; (4 tumor p53 status; (5 PI3K pathway activation in pre-malignant tissue; (6 therapeutic effects on tumors; (7 embryonic stem cell differentiation; (8 the heart under fasting. Together, our work demonstrated that the tissue redox indices obtained from the redox scanning technique may provide useful information about tissue metabolism and physiology status in normal

  16. Adipocytokines, hepatic and inflammatory biomarkers and incidence of type 2 diabetes. the CoLaus study.

    Directory of Open Access Journals (Sweden)

    Pedro Marques-Vidal

    Full Text Available CONTEXT: There is contradictory information regarding the prognostic importance of adipocytokines, hepatic and inflammatory biomarkers on the incidence of type 2 diabetes. The objective was to assess the prognostic relevance of adipocytokine and inflammatory markers (C-reactive protein - CRP; interleukin-1beta - IL-1β; interleukin-6- IL-6; tumour necrosis factor-α - TNF-α; leptin and adiponectin and gamma-glutamyl transpeptidase (γGT on the incidence of type 2 diabetes. METHODS: Prospective, population-based study including 3,842 non-diabetic participants (43.3% men, age range 35 to 75 years, followed for an average of 5.5 years (2003-2008. The endpoint was the occurrence of type 2 diabetes. RESULTS: 208 participants (5.4%, 66 women developed type 2 diabetes during follow-up. On univariate analysis, participants who developed type 2 diabetes had significantly higher baseline levels of IL-6, CRP, leptin and γGT, and lower levels of adiponectin than participants who remained free of type 2 diabetes. After adjusting for a validated type 2 diabetes risk score, only the associations with adiponectin: Odds Ratio and (95% confidence interval: 0.97 (0.64-1.47, 0.84 (0.55-1.30 and 0.64 (0.40-1.03 for the second, third and forth gender-specific quartiles respectively, remained significant (P-value for trend = 0.05. Adding each marker to a validated type 2 diabetes risk score (including age, family history of type 2 diabetes, height, waist circumference, resting heart rate, presence of hypertension, HDL cholesterol, triglycerides, fasting glucose and serum uric acid did not improve the area under the ROC or the net reclassification index; similar findings were obtained when the markers were combined, when the markers were used as continuous (log-transformed variables or when gender-specific quartiles were used. CONCLUSION: Decreased adiponectin levels are associated with an increased risk for incident type 2 diabetes, but they seem to add little

  17. MortalityPredictors.org: a manually-curated database of published biomarkers of human all-cause mortality.

    Science.gov (United States)

    Peto, Maximus V; De la Guardia, Carlos; Winslow, Ksenia; Ho, Andrew; Fortney, Kristen; Morgen, Eric

    2017-08-31

    Biomarkers of all-cause mortality are of tremendous clinical and research interest. Because of the long potential duration of prospective human lifespan studies, such biomarkers can play a key role in quantifying human aging and quickly evaluating any potential therapies. Decades of research into mortality biomarkers have resulted in numerous associations documented across hundreds of publications. Here, we present MortalityPredictors.org , a manually-curated, publicly accessible database, housing published, statistically-significant relationships between biomarkers and all-cause mortality in population-based or generally healthy samples. To gather the information for this database, we searched PubMed for appropriate research papers and then manually curated relevant data from each paper. We manually curated 1,576 biomarker associations, involving 471 distinct biomarkers. Biomarkers ranged in type from hematologic (red blood cell distribution width) to molecular (DNA methylation changes) to physical (grip strength). Via the web interface, the resulting data can be easily browsed, searched, and downloaded for further analysis. MortalityPredictors.org provides comprehensive results on published biomarkers of human all-cause mortality that can be used to compare biomarkers, facilitate meta-analysis, assist with the experimental design of aging studies, and serve as a central resource for analysis. We hope that it will facilitate future research into human mortality and aging.

  18. Comprehensive Care

    Science.gov (United States)

    ... Comprehensive Care Share this page Facebook Twitter Email Comprehensive Care Understand the importance of comprehensive MS care ... In this article A complex disease requires a comprehensive approach Today multiple sclerosis (MS) is not a ...

  19. Biomarkers of the Dementia

    Directory of Open Access Journals (Sweden)

    Mikio Shoji

    2011-01-01

    Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

  20. The role of action knowledge in the comprehension of artefacts - a PET study

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, Ian; Gade, Anders

    2002-01-01

    and two naming tasks divided by category (natural objects vs artefacts). The left PMv (BA 6/44) was more activated by the categorization task for artefacts than by the categorization task for natural objects and the naming task for artefacts. However, the left PMv was not associated with the contrast......Activation of the left ventral premotor cortex (PMv) has in previous imaging studies been associated with the processing of visually presented artefacts. It has been suggested that this activation reflects processing of action knowledge and that action knowledge contributes to the comprehension...... of artefacts. The purpose of the present study was to test whether activation of the left PMv is common for all tasks involving the comprehension of artefacts or whether it is task specific. This was done by comparing performance and regional cerebral blood flow (rCBF) associated with two categorization tasks...

  1. Relating biomarkers to whole-organism effects using species sensitivity distributions : A pilot study for marine species exposed to oil

    NARCIS (Netherlands)

    Smit, M.G.D.; Bechmann, R.K.; Hendriks, A.J.; Skadsheim, A.; Larsen, B.K.; Baussant, T.; Bamber, S.; Sannei, S.

    2009-01-01

    Biomarkers are widely used to measure environmental impacts on marine species. For many biomarkers, it is not clear how the signal levels relate to effects on the whole organism. This paper shows how species sensitivity distributions (SSDs) can be applied to evaluate multiple biomarker responses in

  2. Cognitive Modules Utilized for Narrative Comprehension in Children: A Functional Magnetic Resonance Imaging Study

    OpenAIRE

    Schmithorst, Vincent J.; Holland, Scott K.; Plante, Elena

    2005-01-01

    The ability to comprehend narratives constitutes an important component of human development and experience. The neural correlates of auditory narrative comprehension in children were investigated in a large-scale functional magnetic resonance imaging (fMRI) study involving 313 subjects ages 5–18. Using group Independent Component Analysis (ICA), bilateral task-related components were found comprising the primary auditory cortex, the mid-superior temporal gyrus, the hippocampus, the angular g...

  3. Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study

    OpenAIRE

    Le Quesne Stabej, Polona; Saihan, Zubin; Rangesh, Nell; Steele-Stallard, Heather B; Ambrose, John; Coffey, Alison; Emmerson, Jenny; Haralambous, Elene; Hughes, Yasmin; Steel, Karen P; Luxon, Linda M; Webster, Andrew R; Bitner-Glindzicz, Maria

    2011-01-01

    Background Usher syndrome (USH) is an autosomal recessive disorder comprising retinitis pigmentosa, hearing loss and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous with three distinctive clinical types (I?III) and nine Usher genes identified. This study is a comprehensive clinical and genetic analysis of 172 Usher patients and evaluates the contribution of digenic inheritance. Methods The genes MYO7A, USH1C, CDH23, PCDH15, USH1G, USH2A, GPR98, WHRN, CLR...

  4. Enhancing Social Studies Vocabulary and Comprehension for Seventh-Grade English Language Learners: Findings from Two Experimental Studies

    Science.gov (United States)

    Vaughn, Sharon; Martinez, Leticia R.; Linan-Thompson, Sylvia; Reutebuch, Colleen K.; Carlson, Coleen D.; Francis, David J.

    2009-01-01

    Two experimental studies to improve vocabulary knowledge and comprehension were conducted in 7th-grade social studies classes with English language learners (ELLs). Two different nonoverlapping samples of classes of 7th-grade students (N = 381 and N = 507) were randomly assigned at the classroom (i.e., section) level to a social studies…

  5. Biomarkers for Wilms Tumor: a Systematic Review

    Science.gov (United States)

    Cone, Eugene B.; Dalton, Stewart S.; Van Noord, Megan; Tracy, Elizabeth T.; Rice, Henry E.; Routh, Jonathan C.

    2016-01-01

    Purpose Wilms tumor is the most common childhood renal malignancy and the fourth most common childhood cancer. Many biomarkers have been studied but there has been no comprehensive summary. We systematically reviewed the literature on biomarkers in Wilms Tumor with the objective of quantifying the prognostic implication of the presence of individual tumor markers. Methods We searched for English language studies from 1980–2015 performed on children with Wilms Tumor under 18 years old with prognostic data. The protocol was conducted as per PRISMA guidelines. Two reviewers abstracted data in duplicate using a standard evaluation form. We performed descriptive statistics, then calculated relative risks and 95% confidence intervals for markers appearing in multiple level 2 or 3 studies. Results 40 studies were included examining 32 biomarkers in 7381 Wilms patients. Studies had a median of 61 patients with 24 biomarker positive patients per study, and a median follow-up of 68.4 months. Median percent of patients in Stage 1, 2, 3, 4, and 5 were 28.5%, 26.4%, 24.5%, 14.1%, and 1.7%, with 10.2% anaplasia. The strongest negative prognostic association was loss of heterozygosity on 11p15, with a risk of recurrence of 5.00, although loss of heterozygosity on 1p and gain of function on 1q were also strongly linked to increased recurrence (2.93 and 2.86 respectively). Conclusions Several tumor markers are associated with an increased risk of recurrence or a decreased risk of overall survival in Wilms Tumor. These data suggest targets for development of diagnostic tests and potential therapies. PMID:27259655

  6. Can Prostate Specific Antigen Be Used as New Biomarker for Early Diagnosis of Breast Cancer?

    Directory of Open Access Journals (Sweden)

    Seyed Mostafa Shiryazdi

    2015-09-01

    Conclusion: Plasma PSA level is not a reliable biomarker to diagnose breast cancer, though regarding existing scientific evidence, more comprehensive studies are required to consider other features of malignant samples so as to evaluate the role of PSA in differentiating breast neoplastic lesions in a more meticulous way based on the degree of tumor differentiation.

  7. Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies.

    Science.gov (United States)

    Fernandes, Brisa S; Molendijk, Marc L; Köhler, Cristiano A; Soares, Jair C; Leite, Cláudio Manuel G S; Machado-Vieira, Rodrigo; Ribeiro, Thamara L; Silva, Jéssica C; Sales, Paulo M G; Quevedo, João; Oertel-Knöchel, Viola; Vieta, Eduard; González-Pinto, Ana; Berk, Michael; Carvalho, André F

    2015-11-30

    The neurotrophic hypothesis postulates that mood disorders such as bipolar disorder (BD) are associated with a lower expression of brain-derived neurotrophic factor (BDNF). However, its role in peripheral blood as a biomarker of disease activity and of stage for BD, transcending pathophysiology, is still disputed. In the last few years an increasing number of clinical studies assessing BDNF in serum and plasma have been published. Therefore, it is now possible to analyse the association between BDNF levels and the severity of affective symptoms in BD as well as the effects of acute drug treatment of mood episodes on BDNF levels. We conducted a systematic review and meta-analysis of all studies on serum and plasma BDNF levels in bipolar disorder. Through a series of meta-analyses including a total of 52 studies with 6,481 participants, we show that, compared to healthy controls, peripheral BDNF levels are reduced to the same extent in manic (Hedges' g = -0.57, P = 0.010) and depressive (Hedges' g = -0.93, P = 0.001) episodes, while BDNF levels are not significantly altered in euthymia. In meta-regression analyses, BDNF levels additionally negatively correlate with the severity of both manic and depressive symptoms. We found no evidence for a significant impact of illness duration on BDNF levels. In addition, in plasma, but not serum, peripheral BDNF levels increase after the successful treatment of an acute mania episode, but not of a depressive one. In summary, our data suggest that peripheral BDNF levels, more clearly in plasma than in serum, is a potential biomarker of disease activity in BD, but not a biomarker of stage. We suggest that peripheral BDNF may, in future, be used as a part of a blood protein composite measure to assess disease activity in BD.

  8. Integrated Comprehensive Care - A Case Study in Nursing Leadership and System Transformation.

    Science.gov (United States)

    Wheatley, Laura; Doyle, Winnie; Evans, Cheryl; Gosse, Carolyn; Smith, Kevin

    2017-01-01

    Calls for transformational change of our healthcare system are increasingly clear, persuasive and insistent. They resonate at all levels, with those who fund, deliver, provide and receive care, and they are rooted in a deep understanding that the system, as currently rigidly structured, most often lacks the necessary flexibility to comprehensively meet the needs of patients across the continuum of care. The St. Joseph's Health System (SJHS) Integrated Comprehensive Care (ICC) Program, which bundles care and funding across the hospital to home continuum, has reduced fragmentation of care, and it has delivered improved outcomes for patients, providers and the system. This case study explores the essential contribution of nursing leadership to this successful transformation of healthcare service delivery.

  9. Pedagogical Practices in Teaching Reading Comprehension: A Case Study of Three EFL Teachers in a Secondary School in Ethiopia

    Science.gov (United States)

    Nurie, Yenus

    2017-01-01

    Various studies investigating psychological variables associated with reading comprehension are currently available. However, there has been little linguistic research conducted to examine the pedagogical practices of teachers in teaching reading comprehension of EFL Secondary Schools, Ethiopia. The present study was conducted to fill the research…

  10. The Impact of Gloss Types on Reading Comprehension, Vocabulary Gain and Vocabulary Retention: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Atefeh Elekaei

    2015-09-01

    Full Text Available The significance and impact of vocabulary learning in reading comprehension and L2 language learning are apparent to teachers, researchers and language learners. Moreover, glosses are found as one of the most effective strategies regarding vocabulary retention. Therefore, the present study attempted to investigate the effect of different types of glosses on reading comprehension, vocabulary gain and vocabulary retention. To this end, 140 Iranian EFL learners learning English were selected and were divided into four groups (footnote gloss group, interlinear gloss group, marginal gloss group, and glossary group. They were required to read a text and answer four reading comprehension questions. In addition, one immediate vocabulary post-test and one delayed vocabulary post-test were taken in order to investigate learners' vocabulary gain and vocabulary retention. In order to analyze the data, one one-way ANOVA and one MANOVA were run. The results of one-way ANOVA revealed that participants who received interlinear glosses significantly outperformed the other groups regarding comprehending the text. Moreover, the immediate vocabulary post-test was conducted immediately after reading test and the delayed post-test was administered after four weeks. The results of MANOVA indicated that the group which received interlinear glosses outperformed the other groups in both vocabulary gain and vocabulary retention. The present study has implications for teachers and learners. Teachers can find better methods to teach new reading passages as well as vocabulary items. Also, glosses help learners to have a better comprehension of difficult passages and they facilitate learning. Moreover, learners can enhance their vocabulary knowledge with the help of glosses.

  11. Comprehensive cooling water study annual report. Volume II: introduction and site description, Savannah River Plant

    International Nuclear Information System (INIS)

    Gladden, J.B.; Lower, M.W.; Mackey, H.E.; Specht, W.L.; Wilde, E.W.

    1985-07-01

    The Comprehensive Cooling Water Study was initiated in 1983 to evaluate the environmental effecs of the intake and release of cooling water on the structure and function of aquatic ecosystems at the Savannah River Plant. This report presents the results from the first year of the two year study and also summarizes results from previous studies on aquatic ecosystems of the Savannah River Plant. Five major program elements are addressed: water quality, radionuclide and heavy metal transport, wetlands ecology, aquatic ecology, and endangered species. 63 refs., 13 figs., 7 tabs

  12. Analysis of Plasma Albumin, Vitamin D, and Apolipoproteins A and B as Predictive Coronary Risk Biomarkers in the REGICOR Study.

    Science.gov (United States)

    Vázquez-Oliva, Gabriel; Zamora, Alberto; Ramos, Rafel; Subirana, Isaac; Grau, María; Dégano, Irene R; Muñoz, Daniel; Fitó, Montserrat; Elosua, Roberto; Marrugat, Jaume

    2018-05-12

    New biomarkers could improve the predictive capacity of classic risk functions. The aims of this study were to determine the association between circulating levels of apolipoprotein A1 (apoA1), apolipoprotein B (apoB), albumin, and 25-OH-vitamin D and coronary events and to analyze whether these biomarkers improve the predictive capacity of the Framingham-REGICOR risk function. A case-cohort study was designed. From an initial cohort of 5404 individuals aged 35 to 74 years with a 5-year follow-up, all the participants who had a coronary event (n = 117) and a random group of the cohort (subcohort; n = 667) were selected. Finally, 105 cases and 651 individuals representative of the cohort with an available biological sample were included. The events of interest were angina, fatal and nonfatal myocardial infarction and coronary deaths. Case participants were older, had a higher proportion of men and cardiovascular risk factors, and showed higher levels of apoB and lower levels of apoA1, apoA1/apoB ratio, 25-OH-vitamin D and albumin than the subcohort. In multivariate analyses, plasma albumin concentration was the only biomarker independently associated with coronary events (HR, 0.73; P = .002). The inclusion of albumin in the risk function properly reclassified a significant proportion of individuals, especially in the intermediate risk group (net reclassification improvement, 32.3; P = .048). Plasma albumin levels are inversely associated with coronary risk and improve the predictive capacity of classic risk functions. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  13. Exploratory Studies on Biomarkers: An Example Study on Brown Adipose Tissue

    Science.gov (United States)

    Watanabe, Masahiro; Yamazaki, Naoshi; Kataoka, Masatoshi; Shinohara, Yasuo

    In mammals, two kinds of adipose tissue are known to exist, i.e., white (WAT) and brown (BAT) adipose tissue. The physiological role of WAT is storage of excess energy as fat, whereas that of BAT is the expenditure of excess energy as heat. The uncoupling protein UCP1, which is specifically expressed in brown fat mitochondria, dissipates the proton electrochemical potential across the inner mitochondrial membrane, known as a driving force of ATP synthesis, and thus it dissipates excess energy in a form of heat. Because deficiency in effective expenditure of excess energy causes accumulation of this energy in the form of fat (i.e., obesity), it is very important to understand the energy metabolism in this tissue for the development of anti-obesity drugs. In this article, in addition to providing a brief introduction to the functional properties of BAT and UCP1, the results of our exploratory studies on protein components involved in the energy-dissipating function in BAT.

  14. The Effect of Clown Intervention on Self-Report and Biomarker Measures of Stress and Fatigue in Pediatric Osteosarcoma Inpatients: A Pilot Study.

    Science.gov (United States)

    Lopes-Júnior, Luis C; Pereira-da-Silva, Gabriela; Silveira, Denise S C; Veronez, Luciana C; Santos, Jéssica C; Alonso, Jonas B; Lima, Regina A G

    2018-06-01

    Pediatric cancer patients experience different psychological processes during hospitalization that may regulate the immune response and affect recovery and response to cancer treatment. In this study, we aimed to examine the feasibility of longitudinal testing of psychophysiological parameters of stress and fatigue in pediatric osteosarcoma patients hospitalized for chemotherapy submitted to clown intervention; and to investigate whether changes in the levels of biomarkers are associated with psychological stress and fatigue levels in these patients after the clown intervention. A pretest-posttest quasi-experimental pilot study was conducted at the pediatric oncology inpatient unit in a comprehensive cancer care center in Brazil including children and adolescents with osteosarcoma hospitalized for chemotherapy. Eight saliva samples were collected, comprising 4 at baseline (pre-intervention) and 4 after the clown intervention (+1, +4, +9, and +13 hours post-awakening). Salivary cortisol, α-amylase (sAA), cytokines, and matrix metalloproteinase-9 (MMP-9) levels were determined using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Stress and fatigue were measured by Child Stress Scale-ESI and PedsQL Multidimensional Fatigue Scale respectively. Bivariate association analysis between stress and fatigue scores and biomarker levels were investigated using nonparametric statistics. Effect sizes were calculated for each outcome variable. Six pediatric osteosarcoma patients were enrolled with no missing data. No significant effects sizes were observed for psychophysiological outcomes. Effect sizes ranged from 0.54 (cortisol) to 0 (interleukin-1β [IL-1β]). Decreasing overall trends were observed for cortisol levels for all 6 pediatric osteosarcoma patients over time. In addition, a similar pattern of tumor necrosis factor-α (TNF-α) levels over time was found for all 6 patients. Patients with metastatic osteosarcoma showed a linear trend for a decrease in

  15. Applying Data-driven Imaging Biomarker in Mammography for Breast Cancer Screening: Preliminary Study.

    Science.gov (United States)

    Kim, Eun-Kyung; Kim, Hyo-Eun; Han, Kyunghwa; Kang, Bong Joo; Sohn, Yu-Mee; Woo, Ok Hee; Lee, Chan Wha

    2018-02-09

    We assessed the feasibility of a data-driven imaging biomarker based on weakly supervised learning (DIB; an imaging biomarker derived from large-scale medical image data with deep learning technology) in mammography (DIB-MG). A total of 29,107 digital mammograms from five institutions (4,339 cancer cases and 24,768 normal cases) were included. After matching patients' age, breast density, and equipment, 1,238 and 1,238 cases were chosen as validation and test sets, respectively, and the remainder were used for training. The core algorithm of DIB-MG is a deep convolutional neural network; a deep learning algorithm specialized for images. Each sample (case) is an exam composed of 4-view images (RCC, RMLO, LCC, and LMLO). For each case in a training set, the cancer probability inferred from DIB-MG is compared with the per-case ground-truth label. Then the model parameters in DIB-MG are updated based on the error between the prediction and the ground-truth. At the operating point (threshold) of 0.5, sensitivity was 75.6% and 76.1% when specificity was 90.2% and 88.5%, and AUC was 0.903 and 0.906 for the validation and test sets, respectively. This research showed the potential of DIB-MG as a screening tool for breast cancer.

  16. Cell Electrical Impedance as a Novel Approach for Studies on Senescence Not Based on Biomarkers

    Directory of Open Access Journals (Sweden)

    Jung-Joon Cha

    2016-01-01

    Full Text Available Senescence of cardiac myocytes is frequently associated with heart diseases. To analyze senescence in cardiac myocytes, a number of biomarkers have been isolated. However, due to the complex nature of senescence, multiple markers are required for a single assay to accurately depict complex physiological changes associated with senescence. In single cells, changes in both cytoplasm and cell membrane during senescence can affect the changes in electrical impedance. Based on this phenomenon, we developed MEDoS, a novel microelectrochemical impedance spectroscopy for diagnosis of senescence, which allows us to precisely measure quantitative changes in electrical properties of aging cells. Using cardiac myocytes isolated from 3-, 6-, and 18-month-old isogenic zebrafish, we examined the efficacy of MEDoS and showed that MEDoS can identify discernible changes in electrical impedance. Taken together, our data demonstrated that electrical impedance in cells at different ages is distinct with quantitative values; these results were comparable with previously reported ones. Therefore, we propose that MEDoS be used as a new biomarker-independent methodology to obtain quantitative data on the biological senescence status of individual cells.

  17. NMR studies of preimplantation embryo metabolism in human assisted reproductive techniques: a new biomarker for assessment of embryo implantation potential.

    Science.gov (United States)

    Pudakalakatti, Shivanand M; Uppangala, Shubhashree; D'Souza, Fiona; Kalthur, Guruprasad; Kumar, Pratap; Adiga, Satish Kumar; Atreya, Hanudatta S

    2013-01-01

    There has been growing interest in understanding energy metabolism in human embryos generated using assisted reproductive techniques (ART) for improving the overall success rate of the method. Using NMR spectroscopy as a noninvasive tool, we studied human embryo metabolism to identify specific biomarkers to assess the quality of embryos for their implantation potential. The study was based on estimation of pyruvate, lactate and alanine levels in the growth medium, ISM1, used in the culture of embryos. An NMR study involving 127 embryos from 48 couples revealed that embryos transferred on Day 3 (after 72 h in vitro culture) with successful implantation (pregnancy) exhibited significantly (p < 10(-5) ) lower pyruvate/alanine ratios compared to those that failed to implant. Lactate levels in media were similar for all embryos. This implies that in addition to lactate production, successfully implanted embryos use pyruvate to produce alanine and other cellular functions. While pyruvate and alanine individually have been used as biomarkers, the present study highlights the potential of combining them to provide a single parameter that correlates strongly with implantation potential. Copyright © 2012 John Wiley & Sons, Ltd.

  18. A practical platform for blood biomarker study by using global gene expression profiling of peripheral whole blood.

    Directory of Open Access Journals (Sweden)

    Ze Tian

    Full Text Available Although microarray technology has become the most common method for studying global gene expression, a plethora of technical factors across the experiment contribute to the variable of genome gene expression profiling using peripheral whole blood. A practical platform needs to be established in order to obtain reliable and reproducible data to meet clinical requirements for biomarker study.We applied peripheral whole blood samples with globin reduction and performed genome-wide transcriptome analysis using Illumina BeadChips. Real-time PCR was subsequently used to evaluate the quality of array data and elucidate the mode in which hemoglobin interferes in gene expression profiling. We demonstrated that, when applied in the context of standard microarray processing procedures, globin reduction results in a consistent and significant increase in the quality of beadarray data. When compared to their pre-globin reduction counterparts, post-globin reduction samples show improved detection statistics, lowered variance and increased sensitivity. More importantly, gender gene separation is remarkably clearer in post-globin reduction samples than in pre-globin reduction samples. Our study suggests that the poor data obtained from pre-globin reduction samples is the result of the high concentration of hemoglobin derived from red blood cells either interfering with target mRNA binding or giving the pseudo binding background signal.We therefore recommend the combination of performing globin mRNA reduction in peripheral whole blood samples and hybridizing on Illumina BeadChips as the practical approach for biomarker study.

  19. Epigenome-Wide Association Study Identifies Cardiac Gene Patterning and a Novel Class of Biomarkers for Heart Failure.

    Science.gov (United States)

    Meder, Benjamin; Haas, Jan; Sedaghat-Hamedani, Farbod; Kayvanpour, Elham; Frese, Karen; Lai, Alan; Nietsch, Rouven; Scheiner, Christina; Mester, Stefan; Bordalo, Diana Martins; Amr, Ali; Dietrich, Carsten; Pils, Dietmar; Siede, Dominik; Hund, Hauke; Bauer, Andrea; Holzer, Daniel Benjamin; Ruhparwar, Arjang; Mueller-Hennessen, Matthias; Weichenhan, Dieter; Plass, Christoph; Weis, Tanja; Backs, Johannes; Wuerstle, Maximilian; Keller, Andreas; Katus, Hugo A; Posch, Andreas E

    2017-10-17

    Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with dilated cardiomyopathy and controls. Infinium human methylation 450 was used for high-density epigenome-wide mapping of DNA methylation in left-ventricular biopsies and whole peripheral blood of living probands. RNA deep sequencing was performed on the same samples in parallel. Whole-genome sequencing of all patients allowed exclusion of promiscuous genotype-induced methylation calls. In the screening stage, we detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy (false discovery corrected P ≤0.05), with 3 of them reaching epigenome-wide significance at P ≤5×10 -8 . Twenty-seven (46%) of these loci could be replicated in independent cohorts, underlining the role of epigenetic regulation of key cardiac transcription regulators. Using a staged multi-omics study design, we link a subset of 517 epigenetic loci with dilated cardiomyopathy and cardiac gene expression. Furthermore, we identified distinct epigenetic methylation patterns that are conserved across tissues, rendering these CpGs novel epigenetic biomarkers for heart failure. The present study provides to our knowledge the first epigenome-wide association study in living patients with heart failure using a multi-omics approach. © 2017 American Heart Association, Inc.

  20. Syntactic comprehension in reading and listening: a study with French children with dyslexia.

    Science.gov (United States)

    Casalis, Séverine; Leuwers, Christel; Hilton, Heather

    2013-01-01

    This study examined syntactic comprehension in French children with dyslexia in both listening and reading. In the first syntactic comprehension task, a partial version of the Epreuve de Compréhension syntaxico-sémantique (ECOSSE test; French adaptation of Bishop's test for receptive grammar test) children with dyslexia performed at a lower level in the written but not in the spoken modality, compared to reading age-matched children, suggesting a difficulty in handling syntax while reading. In the second task, syntactic processing was further explored through a test of relative clause processing, in which inflectional markers could aid in attributing roles to the elements in a complex syntactic structure. Children with dyslexia were insensitive to inflectional markers in both reading and listening, as was the reading age control group, while only the older normal reader group appeared to make use of the inflectional markers. Overall, the results support the hypothesis that difficulties in comprehension in dyslexia are strongly related to poor reading skills.

  1. Creating a comprehensive customer service program to help convey critical and acute results of radiology studies.

    Science.gov (United States)

    Towbin, Alexander J; Hall, Seth; Moskovitz, Jay; Johnson, Neil D; Donnelly, Lane F

    2011-01-01

    Communication of acute or critical results between the radiology department and referring clinicians has been a deficiency of many radiology departments. The failure to perform or document these communications can lead to poor patient care, patient safety issues, medical-legal issues, and complaints from referring clinicians. To mitigate these factors, a communication and documentation tool was created and incorporated into our departmental customer service program. This article will describe the implementation of a comprehensive customer service program in a hospital-based radiology department. A comprehensive customer service program was created in the radiology department. Customer service representatives were hired to answer the telephone calls to the radiology reading rooms and to help convey radiology results. The radiologists, referring clinicians, and customer service representatives were then linked via a novel workflow management system. This workflow management system provided tools to help facilitate the communication needs of each group. The number of studies with results conveyed was recorded from the implementation of the workflow management system. Between the implementation of the workflow management system on August 1, 2005, and June 1, 2009, 116,844 radiology results were conveyed to the referring clinicians and documented in the system. This accounts for more than 14% of the 828,516 radiology cases performed in this time frame. We have been successful in creating a comprehensive customer service program to convey and document communication of radiology results. This program has been widely used by the ordering clinicians as well as radiologists since its inception.

  2. Sequential Coherence in Sentence Pairs Enhances Imagery during Comprehension: An Individual Differences Study.

    Directory of Open Access Journals (Sweden)

    Carol Madden-Lombardi

    Full Text Available The present study investigates how sequential coherence in sentence pairs (events in sequence vs. unrelated events affects the perceived ability to form a mental image of the sentences for both auditory and visual presentations. In addition, we investigated how the ease of event imagery affected online comprehension (word reading times in the case of sequentially coherent and incoherent sentence pairs. Two groups of comprehenders were identified based on their self-reported ability to form vivid mental images of described events. Imageability ratings were higher and faster for pairs of sentences that described events in coherent sequences rather than non-sequential events, especially for high imagers. Furthermore, reading times on individual words suggested different comprehension patterns with respect to sequence coherence for the two groups of imagers, with high imagers activating richer mental images earlier than low imagers. The present results offer a novel link between research on imagery and discourse coherence, with specific contributions to our understanding of comprehension patterns for high and low imagers.

  3. Enhancing Social Studies Vocabulary and Comprehension for 7th Grade English Language Learners: Findings from Two Experimental Studies

    Science.gov (United States)

    Vaughn, Sharon; Martinez, Leticia R.; Reutebuch, Colleen K.; Carlson, Coleen D.; Thompson, Sylvia L.; Franci, David J.

    2010-01-01

    The authors identified instructional practices associated with improved outcomes for English language learners (ELLs): (1) research-based vocabulary and concept instruction, (2) the use of media to build comprehension and concept knowledge, (3) the use of graphic organizers, and (4) structured peer-pairings. The purpose of our two studies was to…

  4. Plasma lysosphingomyelin demonstrates great potential as a diagnostic biomarker for Niemann-Pick disease type C in a retrospective study.

    Directory of Open Access Journals (Sweden)

    Richard W D Welford

    Full Text Available Niemann-Pick disease type C (NP-C is a devastating, neurovisceral lysosomal storage disorder which is characterised by variable manifestation of visceral signs, progressive neuropsychiatric deterioration and premature death, caused by mutations in the NPC1 and NPC2 genes. Due to the complexity of diagnosis and the availability of an approved therapy in the EU, improved detection of NP-C may have a huge impact on future disease management. At the cellular level dysfunction or deficiency of either the NPC1 or NPC2 protein leads to a complex intracellular endosomal/lysosomal trafficking defect, and organ specific patterns of sphingolipid accumulation. Lysosphingolipids have been shown to be excellent biomarkers of sphingolipidosis in several enzyme deficient lysosomal storage disorders. Additionally, in a recent study the lysosphingolipids, lysosphingomyelin (SPC and glucosylsphingosine (GlcSph, appeared to be elevated in the plasma of three adult NP-C patients. In order to investigate the clinical utility of SPC and GlcSph as diagnostic markers, an in-depth fit for purpose biomarker assay validation for measurement of these biomarkers in plasma by liquid chromatography-tandem mass spectrometry was performed. Plasma SPC and GlcSph are stable and can be measured accurately, precisely and reproducibly. In a retrospective analysis of 57 NP-C patients and 70 control subjects, median plasma SPC and GlcSph were significantly elevated in NP-C by 2.8-fold and 1.4-fold respectively. For miglustat-naïve NP-C patients, aged 2-50 years, the area under the ROC curve was 0.999 for SPC and 0.776 for GlcSph. Plasma GlcSph did not correlate with SPC levels in NP-C patients. The data indicate excellent potential for the use of lysosphingomyelin in NP-C diagnosis, where it could be used to identify NP-C patients for confirmatory genetic testing.

  5. Predictive Biomarkers of Gastroesophageal Reflux Disease and Barrett's Esophagus in World Trade Center Exposed Firefighters: a 15 Year Longitudinal Study.

    Science.gov (United States)

    Haider, Syed H; Kwon, Sophia; Lam, Rachel; Lee, Audrey K; Caraher, Erin J; Crowley, George; Zhang, Liqun; Schwartz, Theresa M; Zeig-Owens, Rachel; Liu, Mengling; Prezant, David J; Nolan, Anna

    2018-02-15

    Gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE), which are prevalent in the World Trade Center (WTC) exposed and general populations, negatively impact quality of life and cost of healthcare. GERD, a risk factor of BE, is linked to obstructive airways disease (OAD). We aim to identify serum biomarkers of GERD/BE, and assess the respiratory and clinical phenotype of a longitudinal cohort of never-smoking, male, WTC-exposed rescue workers presenting with pulmonary symptoms. Biomarkers collected soon after WTC-exposure were evaluated in optimized predictive models of GERD/BE. In the WTC-exposed cohort, the prevalence of BE is at least 6 times higher than in the general population. GERD/BE cases had similar lung function, D LCO , bronchodilator response and long-acting β-agonist use compared to controls. In confounder-adjusted regression models, TNF-α ≥ 6 pg/mL predicted both GERD and BE. GERD was also predicted by C-peptide ≥ 360 pg/mL, while BE was predicted by fractalkine ≥ 250 pg/mL and IP-10 ≥ 290 pg/mL. Finally, participants with GERD had significantly increased use of short-acting β-agonist compared to controls. Overall, biomarkers sampled prior to GERD/BE presentation showed strong predictive abilities of disease development. This study frames future investigations to further our understanding of aerodigestive pathology due to particulate matter exposure.

  6. Tubulin Beta-3 Chain as a New Candidate Protein Biomarker of Human Skin Aging: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Sylvia G. Lehmann

    2017-01-01

    Full Text Available Skin aging is a complex process, and a lot of efforts have been made to identify new and specific targets that could help to diagnose, prevent, and treat skin aging. Several studies concerning skin aging have analyzed the changes in gene expression, and very few investigations have been performed at the protein level. Moreover, none of these proteomic studies has used a global quantitative labeled proteomic offgel approach that allows a more accurate description of aging phenotype. We applied such an approach on human primary keratinocytes obtained from sun-nonexposed skin biopsies of young and elderly women. A total of 517 unique proteins were identified, and 58 proteins were significantly differentially expressed with 40 that were downregulated and 18 upregulated with aging. Gene ontology and pathway analysis performed on these 58 putative biomarkers of skin aging evidenced that these dysregulated proteins were mostly involved in metabolism and cellular processes such as cell cycle and signaling pathways. Change of expression of tubulin beta-3 chain was confirmed by western blot on samples originated from several donors. Thus, this study suggested the tubulin beta-3 chain has a promising biomarker in skin aging.

  7. Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure

    Directory of Open Access Journals (Sweden)

    Craig Sams

    2016-05-01

    Full Text Available Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i develop a robust analytical method, ii determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii measure the metabolites in samples collected as part of a large investigation of rural residents’ exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%–54% in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents’ study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended.

  8. The Listening Comprehension Strategies Used by College Students to Cope with the Aural Problems in EFL Classes: An Analytical Study

    Science.gov (United States)

    Ghoneim, Nahed Mohamed Mahmoud

    2013-01-01

    The current study focused on the problems which students encounter while listening to the English language, the mental processes they activate in listening comprehension, and the strategies they use in different phases of comprehension. Also, it aimed to find out whether there were any differences between advanced and intermediate students in…

  9. Two novel blood-based biomarker candidates measuring degradation of tau are associated with dementia: A prospective study

    DEFF Research Database (Denmark)

    Neergaard, Jesper Skov; Dragsbæk, Katrine; Christiansen, Claus

    2018-01-01

    fragments were detected in serum of 5,309 women from the Prospective Epidemiological Risk Factor study. The study was an observational, prospective study of Danish postmenopausal women. Subjects were followed with registry-linkage for up to 15 years (median follow-up time 13.7 years). Cox regression......Truncated tau appears to be specifically related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer's disease (AD); however, the relevance of truncated Tau measurements in blood...... is still being studied. The aim of the current study was to assess the longitudinal associations between baseline levels of two novel blood biomarker candidates measuring truncated tau, Tau-A and Tau-C, and the risk of incident dementia and AD in elderly women. Using solid phase competitive ELISA, two tau...

  10. Important considerations in lesion-symptom mapping: Illustrations from studies of word comprehension.

    Science.gov (United States)

    Shahid, Hinna; Sebastian, Rajani; Schnur, Tatiana T; Hanayik, Taylor; Wright, Amy; Tippett, Donna C; Fridriksson, Julius; Rorden, Chris; Hillis, Argye E

    2017-06-01

    Lesion-symptom mapping is an important method of identifying networks of brain regions critical for functions. However, results might be influenced substantially by the imaging modality and timing of assessment. We tested the hypothesis that brain regions found to be associated with acute language deficits depend on (1) timing of behavioral measurement, (2) imaging sequences utilized to define the "lesion" (structural abnormality only or structural plus perfusion abnormality), and (3) power of the study. We studied 191 individuals with acute left hemisphere stroke with MRI and language testing to identify areas critical for spoken word comprehension. We use the data from this study to examine the potential impact of these three variables on lesion-symptom mapping. We found that only the combination of structural and perfusion imaging within 48 h of onset identified areas where more abnormal voxels was associated with more severe acute deficits, after controlling for lesion volume and multiple comparisons. The critical area identified with this methodology was the left posterior superior temporal gyrus, consistent with other methods that have identified an important role of this area in spoken word comprehension. Results have implications for interpretation of other lesion-symptom mapping studies, as well as for understanding areas critical for auditory word comprehension in the healthy brain. We propose that lesion-symptom mapping at the acute stage of stroke addresses a different sort of question about brain-behavior relationships than lesion-symptom mapping at the chronic stage, but that timing of behavioral measurement and imaging modalities should be considered in either case. Hum Brain Mapp 38:2990-3000, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Visceral Fat and Novel Biomarkers of Cardiovascular Disease in Patients With Addison's Disease: A Case-Control Study.

    Science.gov (United States)

    Bergthorsdottir, Ragnhildur; Ragnarsson, Oskar; Skrtic, Stanko; Glad, Camilla A M; Nilsson, Staffan; Ross, Ian Louis; Leonsson-Zachrisson, Maria; Johannsson, Gudmundur

    2017-11-01

    Patients with Addison's disease (AD) have increased cardiovascular mortality. To study visceral fat and conventional and exploratory cardiovascular risk factors in patients with AD. A cross-sectional, single-center, case-control study. Patients (n = 76; n = 51 women) with AD and 76 healthy control subjects were matched for sex, age, body mass index (BMI), and smoking habits. The primary outcome variable was visceral abdominal adipose tissue (VAT) measured using computed tomography. Secondary outcome variables were prevalence of metabolic syndrome (MetS) and 92 biomarkers of cardiovascular disease. The mean ± standard deviation age of all subjects was 53 ± 14 years; mean BMI, 25 ± 4 kg/m2; and mean duration of AD, 17 ± 12 years. The median (range) daily hydrocortisone dose was 30 mg (10 to 50 mg). Median (interquartile range) 24-hour urinary free cortisol excretion was increased in patients vs controls [359 nmol (193 to 601 nmol) vs 175 nmol (140 to 244 nmol); P 1] and vasodilatory protective marker was decreased (FC, <1). Twenty-six patients (34%) vs 12 control subjects (16%) fulfilled the criteria for MetS (P = 0.01). Despite higher cortisol exposure, VAT was not increased in patients with AD. The prevalence of MetS was increased and several biomarkers of cardiovascular disease were adversely affected in patients with AD. Copyright © 2017 Endocrine Society

  12. Bioinformatics tools for the analysis of NMR metabolomics studies focused on the identification of clinically relevant biomarkers.

    Science.gov (United States)

    Puchades-Carrasco, Leonor; Palomino-Schätzlein, Martina; Pérez-Rambla, Clara; Pineda-Lucena, Antonio

    2016-05-01

    Metabolomics, a systems biology approach focused on the global study of the metabolome, offers a tremendous potential in the analysis of clinical samples. Among other applications, metabolomics enables mapping of biochemical alterations involved in the pathogenesis of diseases, and offers the opportunity to noninvasively identify diagnostic, prognostic and predictive biomarkers that could translate into early therapeutic interventions. Particularly, metabolomics by Nuclear Magnetic Resonance (NMR) has the ability to simultaneously detect and structurally characterize an abundance of metabolic components, even when their identities are unknown. Analysis of the data generated using this experimental approach requires the application of statistical and bioinformatics tools for the correct interpretation of the results. This review focuses on the different steps involved in the metabolomics characterization of biofluids for clinical applications, ranging from the design of the study to the biological interpretation of the results. Particular emphasis is devoted to the specific procedures required for the processing and interpretation of NMR data with a focus on the identification of clinically relevant biomarkers. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Is plasma GABA level a biomarker of Post-Traumatic Stress Disorder (PTSD) severity? A preliminary study.

    Science.gov (United States)

    Trousselard, Marion; Lefebvre, Bertrand; Caillet, Lionel; Andruetan, Yann; de Montleau, Franck; Denis, Josiane; Canini, Frédéric

    2016-07-30

    An increased reactivity to the environment is observed in Post-Traumatic Stress Disorder (PTSD). It would be related to impairment of the Gamma Amino Butyric Acid (GABA) neurotransmission. The study aimed to evaluate plasma GABA concentration as a candidate for PTSD severity biomarker. This hypothesis was studied in 17 PTSD patients and 17 healthy Controls using classic and emotional Stroop paradigms. Plasma GABA concentrations were assessed before and after both Stroop tests to evaluate GABA basal tone and GABA reactivity (change in GABAp), respectively. During baseline, PTSD had lower plasma GABA concentrations than the Controls. After the Stroop conflicts GABA reactivity was also lower in PTSD than in the Controls. The GABA baseline tone was negatively correlated with the severity of the PTSD symptoms. This relation was only marginally observed for GABA reactivity. The results produced a trend due to the small size of the sample compared to the number of statistical results given. Altogether, the reduced GABA concentration observed in PTSD could be considered as a possible biomarker for PTSD severity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. A prospective study of fungal biomarkers to improve management of invasive fungal diseases in a mixed specialty critical care unit.

    Science.gov (United States)

    Talento, Alida Fe; Dunne, Katie; Joyce, Eimear Ann; Palmer, Michael; Johnson, Elizabeth; White, P Lewis; Springer, Jan; Loeffler, Juergen; Ryan, Thomas; Collins, Daniel; Rogers, Thomas R

    2017-08-01

    The diagnosis of invasive fungal diseases (IFD) in critical care patients (CrCP) is difficult. The study investigated the performance of a set of biomarkers for diagnosis of IFD in a mixed specialty critical care unit (CrCU). A prospective observational study in patients receiving critical care for ≥7days was performed. Serum samples were tested for the presence of: (1-3) - β-d-glucan (BDG), galactomannan (GM), and Aspergillus fumigatus DNA. GM antigen detection was also performed on bronchoalveolar lavage (BAL) samples. The patients were classified using published definitions for IFD and a diagnostic algorithm for invasive pulmonary aspergillosis. Performance parameters of the assays were determined. In patients with proven and probable IFD, the sensitivity, specificity, PPV and NPV of a single positive BDG were 63%, 83%, 65% and 83% respectively. Specificity increased to 86% with 2 consecutive positive results. The mean BDG value of patients with proven and probable IFD was significantly higher compared to those with fungal colonization and no IFD (p value<0.0001). New diagnostic criteria which incorporate these biomarkers, in particular BDG, and host factors unique to critical care patients should enhance diagnosis of IFD and positively impact antifungal stewardship programs. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Testing audiovisual comprehension tasks with questions embedded in videos as subtitles: a pilot multimethod study

    Directory of Open Access Journals (Sweden)

    Juan Carlos Casañ Núñez

    2017-06-01

    Full Text Available Listening, watching, reading and writing simultaneously in a foreign language is very complex. This paper is part of wider research which explores the use of audiovisual comprehension questions imprinted in the video image in the form of subtitles and synchronized with the relevant fragments for the purpose of language learning and testing. Compared to viewings where the comprehension activity is available only on paper, this innovative methodology may provide some benefits. Among them, it could reduce the conflict in visual attention between watching the video and completing the task, by spatially and temporally approximating the questions and the relevant fragments. The technique is seen as especially beneficial for students with a low proficiency language level. The main objectives of this study were to investigate if embedded questions had an impact on SFL students’ audiovisual comprehension test performance and to find out what examinees thought about them. A multimethod design (Morse, 2003 involving the sequential collection of three quantitative datasets was employed. A total of 41 learners of Spanish as a foreign language (SFL participated in the study (22 in the control group and 19 in the experimental one. Informants were selected by non-probabilistic sampling. The results showed that imprinted questions did not have any effect on test performance. Test-takers’ attitudes towards this methodology were positive. Globally, students in the experimental group agreed that the embedded questions helped them to complete the tasks. Furthermore, most of them were in favour of having the questions imprinted in the video in the audiovisual comprehension test of the final exam. These opinions are in line with those obtained in previous studies that looked into experts’, SFL students’ and SFL teachers’ views about this methodology (Casañ Núñez, 2015a, 2016a, in press-b. On the whole, these studies suggest that this technique has

  16. Sugar-Binding Profiles of Chitin-Binding Lectins from the Hevein Family: A Comprehensive Study

    Directory of Open Access Journals (Sweden)

    Yoko Itakura

    2017-05-01

    Full Text Available Chitin-binding lectins form the hevein family in plants, which are defined by the presence of single or multiple structurally conserved GlcNAc (N-acetylglucosamine-binding domains. Although they have been used as probes for chito-oligosaccharides, their detailed specificities remain to be investigated. In this study, we analyzed six chitin-binding lectins, DSA, LEL, PWM, STL, UDA, and WGA, by quantitative frontal affinity chromatography. Some novel features were evident: WGA showed almost comparable affinity for pyridylaminated chitotriose and chitotetraose, while LEL and UDA showed much weaker affinity, and DSA, PWM, and STL had no substantial affinity for the former. WGA showed selective affinity for hybrid-type N-glycans harboring a bisecting GlcNAc residue. UDA showed extensive binding to high-mannose type N-glycans, with affinity increasing with the number of Man residues. DSA showed the highest affinity for highly branched N-glycans consisting of type II LacNAc (N-acetyllactosamine. Further, multivalent features of these lectins were investigated by using glycoconjugate and lectin microarrays. The lectins showed substantial binding to immobilized LacNAc as well as chito-oligosaccharides, although the extents to which they bound varied among them. WGA showed strong binding to heavily sialylated glycoproteins. The above observations will help interpret lectin-glycoprotein interactions in histochemical studies and glyco-biomarker investigations.

  17. Exploring the usefulness of comprehensive care plans for children with medical complexity (CMC: a qualitative study

    Directory of Open Access Journals (Sweden)

    Adams Sherri

    2013-01-01

    Full Text Available Abstract Background The Medical Home model recommends that Children with Special Health Care Needs (CSHCN receive a medical care plan, outlining the child’s major medical issues and care needs to assist with care coordination. While care plans are a primary component of effective care coordination, the creation and maintenance of care plans is time, labor, and cost intensive, and the desired content of the care plan has not been studied. The purpose of this qualitative study was to understand the usefulness and desired content of comprehensive care plans by exploring the perceptions of parents and health care providers (HCPs of children with medical complexity (CMC. Methods This qualitative study utilized in-depth semi-structured interviews and focus groups. HCPs (n = 15 and parents (n = 15 of CMC who had all used a comprehensive care plan were recruited from a tertiary pediatric academic health sciences center. Themes were identified through grounded theory analysis of interview and focus group data. Results A multi-dimensional model of perceived care plan usefulness emerged. The model highlights three integral aspects of the care plan: care plan characteristics, activating factors and perceived outcomes of using a care plan. Care plans were perceived as a useful tool that centralized and focused the care of the child. Care plans were reported to flatten the hierarchical relationship between HCPs and parents, resulting in enhanced reciprocal information exchange and strengthened relationships. Participants expressed that a standardized template that is family-centered and includes content relevant to both the medical and social needs of the child is beneficial when integrated into overall care planning and delivery for CMC. Conclusions Care plans are perceived to be a useful tool to both health care providers and parents of CMC. These findings inform the utility and development of a comprehensive care plan template as well as a model of how

  18. Implementing a cumulative supermatrix approach for a comprehensive phylogenetic study of the Teloschistales (Pezizomycotina, Ascomycota)

    DEFF Research Database (Denmark)

    Gaya, Ester; Högnabba, Filip; Holguin, Ángela

    2012-01-01

    The resolution of the phylogenetic relationships within the order Teloschistales (Ascomycota, lichen-forming-fungi), with nearly 2000 known species and outstanding phenotypic diversity, has been hindered by the limitation in the resolving power that single-locus or two-locus phylogenetic studies...... – the Megalosporaceae – which is sister to the mainly rock-inhabiting, cosmopolitan, and species rich Teloschistaceae, with a diversity of growth habits ranging from crustose to fruticose. Our results confirm the use of a cumulative supermatrix approach as a viable method to generate comprehensive phylogenies...

  19. Syntactic and Lexical Complexity of B2 Listening Comprehension Subtests in English: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Ilc Gašper

    2016-12-01

    Full Text Available Adopting Weir’s (2005 socio-cognitive validation framework, the present paper focuses on the syntactic and lexical complexity of listening comprehension subtests in three B2-level examinations: The City Guilds international examination in English, The First Certificate in English, and the General Matura in English. By analysing and interpreting the results obtained from different automated tools, the research aims to determine to what extent the three subtests are comparable. The results of the study suggest the unreliability of the Common European Framework of Reference for Languages (CEFR as a sole mechanism for test comparisons.

  20. Study on comprehensive evaluation model for nuclear power plant control room layout

    International Nuclear Information System (INIS)

    Zhu Yiming; Liu Yuan; Fan Huixian

    2010-01-01

    A comprehensive evaluation model for layout of the main control room of nuclear power plants was proposed. Firstly the design scope and principle for the layout of the main control room were defined based on the standards, and then the index system for the comprehensive evaluation was established. Finally, comprehensive evaluation was carried out for the layout design by applying the fuzzy comprehensive evaluation method in the index system. (authors)

  1. Gene expression analysis of 4 biomarker candidates in Eisenia fetida exposed to an environmental metallic trace elements gradient: A microcosm study

    Energy Technology Data Exchange (ETDEWEB)

    Brulle, Franck; Lemiere, Sebastien [Univ Lille Nord de France, F-59000 Lille (France); LGCgE, Equipe Ecologie Numerique et Ecotoxicologie, Lille 1, F-59650 Villeneuve d' Ascq (France); Waterlot, Christophe; Douay, Francis [Univ Lille Nord de France, F-59000 Lille (France); LGCgE, Equipe Sols et Environnement, Groupe ISA, 48 boulevard Vauban, F-59046 Lille Cedex (France); Vandenbulcke, Franck, E-mail: franck.vandenbulcke@univ-lille1.fr [Univ Lille Nord de France, F-59000 Lille (France); LGCgE, Equipe Ecologie Numerique et Ecotoxicologie, Lille 1, F-59650 Villeneuve d' Ascq (France)

    2011-11-15

    Past activities of 2 smelters (Metaleurop Nord and Nyrstar) led to the accumulation of high amounts of Metal Trace Elements (TEs) in top soils of the Noyelles-Godault/Auby area, Northern France. Earthworms were exposed to polluted soils collected in this area to study and better understand the physiological changes, the mechanisms of acclimation, and detoxification resulting from TE exposure. Previously we have cloned and transcriptionally characterized potential biomarkers from immune cells of the ecotoxicologically important earthworm species Eisenia fetida exposed in vivo to TE-spiked standard soils. In the present study, analysis of expression kinetics of four candidate indicator genes (Cadmium-metallothionein, coactosin like protein, phytochelatin synthase and lysenin) was performed in E. fetida after microcosm exposures to natural soils exhibiting an environmental cadmium (Cd) gradient in a kinetic manner. TE body burdens were also measured. This microcosm study provided insights into: (1) the ability of the 4 tested genes to serve as expression biomarkers, (2) detoxification processes through the expression analysis of selected genes, and (3) influence of land uses on the response of potential biomarkers (gene expression or TE uptake). - Highlights: {yields} Expression biomarkers in animals exposed to Cadmium-contaminated field soils. {yields} Expression kinetics to test the ability of genes to serve as expression biomarkers. {yields} Study of detoxification processes through the expression analysis of selected genes.

  2. Validation of standard operating procedures in a multicenter retrospective study to identify -omics biomarkers for chronic low back pain.

    Directory of Open Access Journals (Sweden)

    Concetta Dagostino

    Full Text Available Chronic low back pain (CLBP is one of the most common medical conditions, ranking as the greatest contributor to global disability and accounting for huge societal costs based on the Global Burden of Disease 2010 study. Large genetic and -omics studies provide a promising avenue for the screening, development and validation of biomarkers useful for personalized diagnosis and treatment (precision medicine. Multicentre studies are needed for such an effort, and a standardized and homogeneous approach is vital for recruitment of large numbers of participants among different centres (clinical and laboratories to obtain robust and reproducible results. To date, no validated standard operating procedures (SOPs for genetic/-omics studies in chronic pain have been developed. In this study, we validated an SOP model that will be used in the multicentre (5 centres retrospective "PainOmics" study, funded by the European Community in the 7th Framework Programme, which aims to develop new biomarkers for CLBP through three different -omics approaches: genomics, glycomics and activomics. The SOPs describe the specific procedures for (1 blood collection, (2 sample processing and storage, (3 shipping details and (4 cross-check testing and validation before assays that all the centres involved in the study have to follow. Multivariate analysis revealed the absolute specificity and homogeneity of the samples collected by the five centres for all genetics, glycomics and activomics analyses. The SOPs used in our multicenter study have been validated. Hence, they could represent an innovative tool for the correct management and collection of reliable samples in other large-omics-based multicenter studies.

  3. Pulmonary function and CT biomarkers as risk factors for cardiovascular events in male lung cancer screening participants: the NELSON study

    International Nuclear Information System (INIS)

    Takx, Richard A.P.; Hoesein, Firdaus A.A.M.; Mali, Willem P.T.M.; Leiner, Tim; Jong, Pim A. de; Vliegenthart, Rozemarijn; Isgum, Ivana; Koning, Harry J. de; Aalst, Carlijn M. van der; Zanen, Pieter; Lammers, Jan-Willem J.; Groen, Harry J.M.; Rikxoort, Eva M. van; Ginneken, Bram van; Schmidt, Michael; Oudkerk, Matthijs

    2015-01-01

    The objective of this study was to investigate the association of spirometry and pulmonary CT biomarkers with cardiovascular events. In this lung cancer screening trial 3,080 male participants without a prior cardiovascular event were analysed. Fatal and non-fatal cardiovascular events were included. Spirometry included forced expiratory volume measured in units of one-second percent predicted (FEV 1 %predicted) and FEV 1 divided by forced vital capacity (FVC; FEV 1 /FVC). CT examinations were quantified for coronary artery calcium volume, pulmonary emphysema (perc15) and bronchial wall thickness (pi10). Data were analysed via a Cox proportional hazard analysis, net reclassification improvement (NRI) and C-indices. 184 participants experienced a cardiovascular event during a median follow-up of 2.9 years. Age, pack-years and smoking status adjusted hazard ratios were 0.992 (95 % confidence interval (CI) 0.985-0.999) for FEV 1 %predicted, 1.000 (95%CI 0.986-1.015) for FEV 1 /FVC, 1.014 (95%CI 1.005-1.023) for perc15 per 10 HU, and 1.269 (95%CI 1.024-1.573) for pi10 per 1 mm. The incremental C-index ( 3 , an increase in C-index of 0.076 and an NRI of 16.9 % (P < 0.0001). Pulmonary CT biomarkers and spirometry measurements were significantly associated with cardiovascular events, but did not contain clinically relevant independent prognostic information for cardiovascular events. (orig.)

  4. Rationale and methods of the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF).

    Science.gov (United States)

    Januzzi, James L; Butler, Javed; Fombu, Emmanuel; Maisel, Alan; McCague, Kevin; Piña, Ileana L; Prescott, Margaret F; Riebman, Jerome B; Solomon, Scott

    2018-05-01

    Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor indicated for the treatment of patients with chronic heart failure (HF) with reduced ejection fraction; however, its mechanism of benefit remains unclear. Biomarkers that are linked to ventricular remodeling, myocardial injury, and fibrosis may provide mechanistic insight and important clinical guidance regarding sacubitril/valsartan use. This 52-week, multicenter, open-label, single-arm study is designed to (1) correlate biomarker changes with cardiac remodeling parameters, cardiovascular outcomes, and patient-reported outcome data and (2) determine short- and long-term changes in concentrations of biomarkers related to potential mechanisms of action and effects of sacubitril/valsartan therapy. Approximately 830 patients with HF with reduced ejection fraction will be initiated and titrated on sacubitril/valsartan according to United States prescribing information. Primary efficacy end points include the changes in N-terminal pro-B-type natriuretic peptide concentrations and cardiac remodeling from baseline to 1 year. Secondary end points include changes in concentrations of N-terminal pro-B-type natriuretic peptide and remodeling to 6 months, and changes in patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire-23 from baseline to 1 year. In addition, several other relevant biomarkers will be measured. Biomarker changes relative to the number of cardiovascular events in 12 months will also be assessed as exploratory end points. Results from the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF) will help establish a mechanistic understanding of angiotensin receptor-neprilysin inhibitor therapeutic benefits and provide clinicians with clarity on how to interpret information on biomarkers during treatment (PROVE-HF ClinicalTrials.gov identifier: NCT02887183). Copyright © 2018 The

  5. Does comprehensive redevelopment change the housing price gradient? A case study in Mongkok, Hong Kong

    Directory of Open Access Journals (Sweden)

    Yung Yau

    2011-01-01

    Full Text Available Urban decay is an inevitable outcome of the growth of most cities, including Hong Kong. Many old buildings in Hong Kong are dilapidated, and it is urgent to tackle urban decay in the city. Redeveloping dilapidated buildings has long been regarded as an effective solution to this urban problem. Yet, as suggested in the literature, redevelopment may be responsible for gentrifying neighbourhoods because it pushes up property and rental prices near redeveloped sites. However, there are still few empirical studies on how comprehensive redevelopment affects housing values in a neighbourhood. In this light, this study investigates the impacts of the Urban Renewal Authority’s Argyle Street / Shanghai Street Redevelopment Project on the transaction prices of nearby housing. A set of panel data is employed and the change in the spatial price gradient before and after the redevelopment project is explored. The findings suggest that proximity to the project site had a significant positive impact on housing prices before the project. However, no change was seen in the spatial price gradient after completion of the project. These results confirm the findings of a previous study that housing prices do not respond to the change in the environmental quality resulting from comprehensive redevelopment.

  6. Comprehensive study of flow and heat transfer at the surface of circular cooling fin

    Science.gov (United States)

    Mityakov, V. Yu; Grekov, M. A.; Gusakov, A. A.; Sapozhnikov, S. Z.; Seroshtanov, V. V.; Bashkatov, A. V.; Dymkin, A. N.; Pavlov, A. V.; Milto, O. A.; Kalmykov, K. S.

    2017-11-01

    For the first time is proposed to combine heat flux measurements with thermal imaging and PIV (particle image velocimetry) for a comprehensive study of flow and heat transfer at the surface of the circular cooling fin. The investigated hollow fin is heated from within with saturated water steam; meanwhile the isothermal external surface simulates one of the perfect fin. Flow and heat transfer at the surface of the solid fin of the same size and shape, made of titanium alloy is investigated in the same regimes. Gradient Heat Flux Sensors (GHFS) were installed at different places of the fin surface. Velocity field around a cylinder, temperature field at the surface of the fin and heat flux for each rated time were obtained. Comprehensive method including heat flux measurement, PIV and thermal imaging allow to study flow and heat transfer at the surface of the fin in real time regime. The possibility to study flow and heat transfer for non-isothermal fins is shown; it is allow to improve traditional calculation of the cooling fins.

  7. Multiple Sclerosis Cerebrospinal Fluid Biomarkers

    Directory of Open Access Journals (Sweden)

    Gavin Giovannoni

    2006-01-01

    Full Text Available Cerebrospinal fluid (CSF is the body fluid closest to the pathology of multiple sclerosis (MS. For many candidate biomarkers CSF is the only fluid that can be investigated. Several factors need to be standardized when sampling CSF for biomarker research: time/volume of CSF collection, sample processing/storage, and the temporal relationship of sampling to clinical or MRI markers of disease activity. Assays used for biomarker detection must be validated so as to optimize the power of the studies. A formal method for establishing whether or not a particular biomarker can be used as a surrogate end-point needs to be adopted. This process is similar to that used in clinical trials, where the reporting of studies has to be done in a standardized way with sufficient detail to permit a critical review of the study and to enable others to reproduce the study design. A commitment must be made to report negative studies so as to prevent publication bias. Pre-defined consensus criteria need to be developed for MS-related prognostic biomarkers. Currently no candidate biomarker is suitable as a surrogate end-point. Bulk biomarkers of the neurodegenerative process such as glial fibrillary acidic protein (GFAP and neurofilaments (NF have advantages over intermittent inflammatory markers.

  8. Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer

    International Nuclear Information System (INIS)

    Arcaroli, John; Quackenbush, Kevin; Dasari, Arvind; Powell, Rebecca; McManus, Martine; Tan, Aik-Choon; Foster, Nathan R; Picus, Joel; Wright, John; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A

    2012-01-01

    Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] “top scoring pairs” polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3′ untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible

  9. Dynamics and Trends in Fecal Biomarkers of Gut Function in Children from 1–24 Months in the MAL-ED Study

    Science.gov (United States)

    McCormick, Benjamin J. J.; Lee, Gwenyth O.; Seidman, Jessica C.; Haque, Rashidul; Mondal, Dinesh; Quetz, Josiane; Lima, Aldo A. M.; Babji, Sudhir; Kang, Gagandeep; Shrestha, Sanjaya K.; Mason, Carl J.; Qureshi, Shahida; Bhutta, Zulfiqar A.; Olortegui, Maribel Paredes; Yori, Pablo Peñataro; Samie, Amidou; Bessong, Pascal; Amour, Caroline; Mduma, Estomih; Patil, Crystal L.; Guerrant, Richard L.; Lang, Dennis R.; Gottlieb, Michael; Caulfield, Laura E.; Kosek, Margaret N.

    2017-01-01

    Growth and development shortfalls that are disproportionately prevalent in children living in poor environmental conditions are postulated to result, at least in part, from abnormal gut function. Using data from The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal cohort study, we examine biomarkers of gut inflammation and permeability in relation to environmental exposures and feeding practices. Trends in the concentrations of three biomarkers, myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT), are described from fecal samples collected during the first 2 years of each child's life. A total of 22,846 stool samples were processed during the longitudinal sampling of 2,076 children 0–24 months of age. Linear mixed models were constructed to examine the relationship between biomarker concentrations and recent food intake, symptoms of illness, concurrent enteropathogen infection, and socioeconomic status. Average concentrations of MPO, NEO, and AAT were considerably higher than published references for healthy adults. The concentration of each biomarker tended to decrease over the first 2 years of life and was highly variable between samples from each individual child. Both MPO and AAT were significantly elevated by recent breast milk intake. All three biomarkers were associated with pathogen presence, although the strength and direction varied by pathogen. The interpretation of biomarker concentrations is subject to the context of their collection. Herein, we identify that common factors (age, breast milk, and enteric infection) influence the concentration of these biomarkers. Within the context of low- and middle-income communities, we observe concentrations that indicate gut abnormalities, but more appropriate reference standards are needed. PMID:27994110

  10. Dynamics and Trends in Fecal Biomarkers of Gut Function in Children from 1-24 Months in the MAL-ED Study.

    Science.gov (United States)

    McCormick, Benjamin J J; Lee, Gwenyth O; Seidman, Jessica C; Haque, Rashidul; Mondal, Dinesh; Quetz, Josiane; Lima, Aldo A M; Babji, Sudhir; Kang, Gagandeep; Shrestha, Sanjaya K; Mason, Carl J; Qureshi, Shahida; Bhutta, Zulfiqar A; Olortegui, Maribel Paredes; Yori, Pablo Peñataro; Samie, Amidou; Bessong, Pascal; Amour, Caroline; Mduma, Estomih; Patil, Crystal L; Guerrant, Richard L; Lang, Dennis R; Gottlieb, Michael; Caulfield, Laura E; Kosek, Margaret N

    2017-02-08

    Growth and development shortfalls that are disproportionately prevalent in children living in poor environmental conditions are postulated to result, at least in part, from abnormal gut function. Using data from The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal cohort study, we examine biomarkers of gut inflammation and permeability in relation to environmental exposures and feeding practices. Trends in the concentrations of three biomarkers, myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT), are described from fecal samples collected during the first 2 years of each child's life. A total of 22,846 stool samples were processed during the longitudinal sampling of 2,076 children 0-24 months of age. Linear mixed models were constructed to examine the relationship between biomarker concentrations and recent food intake, symptoms of illness, concurrent enteropathogen infection, and socioeconomic status. Average concentrations of MPO, NEO, and AAT were considerably higher than published references for healthy adults. The concentration of each biomarker tended to decrease over the first 2 years of life and was highly variable between samples from each individual child. Both MPO and AAT were significantly elevated by recent breast milk intake. All three biomarkers were associated with pathogen presence, although the strength and direction varied by pathogen. The interpretation of biomarker concentrations is subject to the context of their collection. Herein, we identify that common factors (age, breast milk, and enteric infection) influence the concentration of these biomarkers. Within the context of low- and middle-income communities, we observe concentrations that indicate gut abnormalities, but more appropriate reference standards are needed. © The American Society of Tropical Medicine and Hygiene.

  11. A comprehensive joint replacement program for total knee arthroplasty: a descriptive study

    Directory of Open Access Journals (Sweden)

    Prefontaine Paul

    2008-11-01

    Full Text Available Abstract Background Total knee arthroplasty (TKA is a commonly performed surgical procedure in the US. It is important to have a comprehensive inpatient TKA program which maximizes outcomes while minimizing adverse events. The purpose of this study was to describe a TKA program – the Joint Replacement Program (JRP – and report post-surgical outcomes. Methods 74 candidates for a primary TKA were enrolled in the JRP. The JRP was designed to minimize complications and optimize patient-centered outcomes using a team approach including the patient, patient's family, and a multidisciplinary team of health professionals. The JRP consisted of a pre-operative class, standard pathways for medical care, comprehensive peri-operative pain management, aggressive physical therapy (PT, and proactive discharge planning. Measures included functional tests, knee range of motion (ROM, and medical record abstraction of patient demographics, length of stay, discharge disposition, and complications over a 6-month follow-up period. Results All patients achieved medical criteria for hospital discharge. The patients achieved the knee flexion ROM goal of 90° (91.7 ± 5.4°, but did not achieve the knee extension ROM goal of 0° (2.4 ± 2.6°. The length of hospital stay was two days for 53% of the patients, with 39% and 7% discharged in three and four days, respectively. All but three patients were discharged home with functional independence. 68% of these received outpatient physical therapy compared with 32% who received home physical therapy immediately after discharge. Two patients ( Conclusion The comprehensive JRP for TKA was associated with satisfactory clinical outcomes, short lengths of stay, a high percentage of patients discharged home with outpatient PT, and minimal complications. This JRP may represent an efficient, effective and safe protocol for providing care after a TKA.

  12. Comprehensive modelling study on observed new particle formation at the SORPES station in Nanjing, China

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    X. Huang

    2016-03-01

    Full Text Available New particle formation (NPF has been investigated intensively during the last 2 decades because of its influence on aerosol population and the possible contribution to cloud condensation nuclei. However, intensive measurements and modelling activities on this topic in urban metropolitan areas in China with frequent high-pollution episodes are still very limited. This study provides results from a comprehensive modelling study on the occurrence of NPF events in the western part of the Yangtze River Delta (YRD region, China. The comprehensive modelling system, which combines the WRF-Chem (the Weather Research and Forecasting model coupled with Chemistry regional chemical transport model and the MALTE-BOX sectional box model (the model to predict new aerosol formation in the lower troposphere, was shown to be capable of simulating atmospheric nucleation and subsequent growth. Here we present a detailed discussion of three typical NPF days, during which the measured air masses were notably influenced by either anthropogenic activities, biogenic emissions, or mixed ocean and continental sources. Overall, simulated NPF events were generally in good agreement with the corresponding measurements, enabling us to get further insights into NPF processes in the YRD region. Based on the simulations, we conclude that biogenic organic compounds, particularly monoterpenes, play an essential role in the initial condensational growth of newly formed clusters through their low-volatility oxidation products. Although some uncertainties remain in this modelling system, this method provides a possibility to better understand particle formation and growth processes.

  13. Use of a urinary sugars biomarker to assess measurement error in self-reported sugars intake in the Nutrition and Physical Activity Assessment Study (NPAAS)

    Science.gov (United States)

    Tasevska, Natasha; Midthune, Douglas; Tinker, Lesley F.; Potischman, Nancy; Lampe, Johanna W.; Neuhouser, Marian L.; Beasley, Jeannette M.; Van Horn, Linda; Prentice, Ross L.; Kipnis, Victor

    2014-01-01

    Background Measurement error (ME) in self-reported sugars intake may be obscuring the association between sugars and cancer risk in nutritional epidemiologic studies. Methods We used 24-hour urinary sucrose and fructose as a predictive biomarker for total sugars, to assess ME in self-reported sugars intake. The Nutrition and Physical Activity Assessment Study (NPAAS) is a biomarker study within the Women’s Health Initiative (WHI) Observational Study, that includes 450 post-menopausal women aged 60–91. Food Frequency Questionnaires (FFQ), 4-day food records (4DFR) and three 24-h dietary recalls (24HRs) were collected along with sugars and energy dietary biomarkers. Results Using the biomarker, we found self-reported sugars to be substantially and roughly equally misreported across the FFQ, 4DFR and 24HR. All instruments were associated with considerable intake- and person-specific bias. Three 24HRs would provide the least attenuated risk estimate for sugars (attenuation factor, AF=0.57), followed by FFQ (AF=0.48), and 4DFR (AF=0.32), in studies of energy-adjusted sugars and disease risk. In calibration models, self-reports explained little variation in true intake (5–6% for absolute sugars; 7–18% for sugars density). Adding participants’ characteristics somewhat improved the percentage variation explained (16–18% for absolute sugars; 29–40% for sugars density). Conclusions None of the self-report instruments provided a good estimate of sugars intake, although overall 24HRs seemed to perform the best. Impact Assuming the calibrated sugars biomarker is unbiased, this analysis suggests that, measuring the biomarker in a subsample of the study population for calibration purposes may be necessary for obtaining unbiased risk estimates in cancer association studies. PMID:25234237

  14. Proteomic and metabolomic approaches to biomarker discovery

    CERN Document Server

    Issaq, Haleem J

    2013-01-01

    Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

  15. Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

    Science.gov (United States)

    Felker, G Michael; Ahmad, Tariq; Anstrom, Kevin J; Adams, Kirkwood F; Cooper, Lawton S; Ezekowitz, Justin A; Fiuzat, Mona; Houston-Miller, Nancy; Januzzi, James L; Leifer, Eric S; Mark, Daniel B; Desvigne-Nickens, Patrice; Paynter, Gayle; Piña, Ileana L; Whellan, David J; O'Connor, Christopher M

    2014-10-01

    The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF. GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of study are followed up at regular intervals and after treatment adjustments for a minimum of 12 months. The primary endpoint of the study is time to cardiovascular death or first hospitalization for HF. Secondary endpoints include time to cardiovascular death and all-cause mortality, cumulative mortality, health-related quality of life, resource use, cost-effectiveness, and safety. The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840). Copyright © 2014 American College of Cardiology Foundation

  16. Metabolomic study of lipids in serum for biomarker discovery in Alzheimer's disease using direct infusion mass spectrometry.

    Science.gov (United States)

    González-Domínguez, R; García-Barrera, T; Gómez-Ariza, J L

    2014-09-01

    In this study, we demonstrated the potential of direct infusion mass spectrometry for the lipidomic characterization of Alzheimer's disease. Serum samples were extracted for lipids recovery, and directly analyzed using an electrospray source. Metabolomic fingerprints were subjected to multivariate analysis in order to discriminate between groups of patients and healthy controls, and then some key-compounds were identified as possible markers of Alzheimer's disease. Major differences were found in lipids, although some low molecular weight metabolites also showed significant changes. Thus, important metabolic pathways involved in neurodegeneration could be studied on the basis of these perturbations, such as membrane breakdown (phospholipids and diacylglycerols), oxidative stress (prostaglandins, imidazole and histidine), alterations in neurotransmission systems (oleamide and putrescine) and hyperammonaemia (guanidine and arginine). Moreover, it is noteworthy that some of these potential biomarkers have not been previously described for Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. A Comprehensive Framework for Information Technology Governance and Localizing it for Automotive Industry of Iran (Case Study: ATLAS Automotive Holding

    Directory of Open Access Journals (Sweden)

    Mohammad Mosakhani

    2017-03-01

    Full Text Available Due to the absence of a comprehensive framework for IT governance, the main objective of the study is to identify all components of IT governance and present them in the form of a comprehensive IT governance framework .The localization of provided framework for the automotive industry is the secondary objective of the study. In this regard, the research questions are: what is the comprehensive framework of IT governance? What are the components and dimensions of a comprehensive framework of IT governance? What is the localized comprehensive framework of IT governance for the Iranian automotive industry? All researches on IT governance were investigated using meta-synthesis qualitative method and were limited to 96 selected articles by performing a meta-synthesis process. Then, the five categories, 19 concepts and 79 codes of IT governance were identified through detailed study of these articles. Then, a comprehensive framework of IT governance was presented. For localizing, a questionnaire designed based on the identified IT governance components, and distributed among the automotive industry experts. Statistical hypothesis testing of collected data led to the rejection of cross/functional job rotation component in the automotive industry. To demonstrate the applicability of the framework, the IT governance status of ATLAS holding company was evaluated based on the comprehensive framework that localized for automotive industry.

  18. Preliminary study on biomarkers for the fungal resistance in Vitis vinifera leaves.

    Science.gov (United States)

    Batovska, Daniela Ilieva; Todorova, Iva Todorova; Nedelcheva, Daniela Valentinova; Parushev, Stoyan Parushev; Atanassov, Atanas Ivanov; Hvarleva, Tzvetanka Dimitrova; Djakova, Galina Jordanova; Bankova, Vassya Stefanova; Popov, Simeon Simeonov

    2008-05-26

    We examined the leaf chemical composition of six seedlings obtained by self-pollination of the Bulgarian wine-making variety Storgozia as well as the cultivar Bouquet, which is the susceptible parent of Storgozia. The chemical composition was investigated in the framework of a program for identification of metabolites associated with disease resistance in grape-vine. Acetone, dichloromethane and butanol extracts, as well as volatiles obtained from fresh material were analyzed by GC/MS. Based on the correlations of the GC/MS data and estimated resistance of the leaves towards the etiological agents of powdery mildew, downy mildew and botrytis as biomarkers for the fungal resistance, we proposed 16 individual metabolites--alpha- and gamma-tocopherol, squalene, alpha-amyrine, stigmasta-3,5-diene-7-one, hexahydrofarnesyl acetone, glycolic acid, 3-hydroxybutanoic acid, 3-hydroxycaproic acid, malic acid, tartaric acid, erythronic acid, arabinoic acid, monoethyl phosphate, undecyl laurate and isopropyl myristate. The obtained correlations were confirmed by cluster analysis.

  19. Factors that contribute to biomarker responses in humans including a study in individuals taking Vitamin C supplementation.

    Science.gov (United States)

    Anderson, D

    2001-09-01

    It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and in the environment. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure-related problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. However, for interpretation of responses, the issue of confounding factors must be addressed. There are endogenous confounding factors, such as age, gender, and genetic make-up and exogenous ones, including lifestyle habits (smoking, drinking, etc.) There are biomarkers of exposure, effect/response and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects on cytogenetic damage and ras oncoproteins will be considered in relation to workers exposed to vinyl chloride and petroleum emissions and to volunteers taking Vitamin C supplementation. Smoking history, exposure and duration of employment affected the worker studies. For petroleum emissions, so did gender and season of exposure. For the non-smoking volunteer Vitamin C supplementation study, cholesterol levels, plasma Vitamin C levels, lipid peroxidation products and DNA damage in the Comet assay were also measured. Gender affected differences in Vitamin C levels, antioxidant capacity and the number of chromosome aberrations induced by bleomycin challenge in vitro. The results were the same for both high and low cholesterol subjects. The relationship between biomarkers and the various factors which

  20. Relationship between inflammatory biomarkers and depressive symptoms during late pregnancy and the early postpartum period: a longitudinal study.

    Science.gov (United States)

    Simpson, William; Steiner, Meir; Coote, Marg; Frey, Benicio N

    2016-01-01

    Perinatal depressive symptoms often co-occur with other inflammatory morbidities of pregnancy. The goals of our study were 1) to examine whether changes in inflammatory markers from the third trimester of pregnancy to 12 weeks postpartum were associated with changes in depressive symptoms; 2) to examine whether third trimester inflammatory markers alone were predictive of postpartum depressive symptoms; and 3) to examine the relationship between inflammatory markers and depressive symptoms during the third trimester of pregnancy and at 12 weeks postpartum. Thirty-three healthy pregnant women were recruited from the Women's Health Concerns Clinic at St. Joseph's Healthcare in Hamilton, Canada. The impact of depressive symptoms on the levels of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) at the third trimester of pregnancy, at 12 weeks postpartum, and across time was assessed using linear and mixed-model regression. Regression analysis revealed no significant association between depressive symptoms and any of the candidate biomarkers during pregnancy, at 12 weeks postpartum, or over time. Pregnancy depressive symptoms (p > 0.001), IL-6 (p = 0.025), and IL-10 (p = 0.006) were significant predictors of postpartum Edinburgh Perinatal Depression Scale (EPDS) score. Our study supports previous reports from the literature showing no relationship between inflammatory biomarkers and depressive symptoms during late pregnancy, early postpartum, or across time. Our study is the first to observe an association between late pregnancy levels of IL-6 and IL-10 and postpartum depressive symptoms. Further studies with larger samples are required to confirm these findings.

  1. Relationship between inflammatory biomarkers and depressive symptoms during late pregnancy and the early postpartum period: a longitudinal study

    Directory of Open Access Journals (Sweden)

    William Simpson

    Full Text Available Objective: Perinatal depressive symptoms often co-occur with other inflammatory morbidities of pregnancy. The goals of our study were 1 to examine whether changes in inflammatory markers from the third trimester of pregnancy to 12 weeks postpartum were associated with changes in depressive symptoms; 2 to examine whether third trimester inflammatory markers alone were predictive of postpartum depressive symptoms; and 3 to examine the relationship between inflammatory markers and depressive symptoms during the third trimester of pregnancy and at 12 weeks postpartum. Methods: Thirty-three healthy pregnant women were recruited from the Women’s Health Concerns Clinic at St. Joseph’s Healthcare in Hamilton, Canada. The impact of depressive symptoms on the levels of interleukin (IL-6, IL-10, tumor necrosis factor alpha (TNF-α, and C-reactive protein (CRP at the third trimester of pregnancy, at 12 weeks postpartum, and across time was assessed using linear and mixed-model regression. Results: Regression analysis revealed no significant association between depressive symptoms and any of the candidate biomarkers during pregnancy, at 12 weeks postpartum, or over time. Pregnancy depressive symptoms (p > 0.001, IL-6 (p = 0.025, and IL-10 (p = 0.006 were significant predictors of postpartum Edinburgh Perinatal Depression Scale (EPDS score. Conclusions: Our study supports previous reports from the literature showing no relationship between inflammatory biomarkers and depressive symptoms during late pregnancy, early postpartum, or across time. Our study is the first to observe an association between late pregnancy levels of IL-6 and IL-10 and postpartum depressive symptoms. Further studies with larger samples are required to confirm these findings.

  2. Comprehensive Dataset and Reports of the Mamala Bay Study during 1993-1995 on Oahu, Hawaii (NODC Accession 0000030)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This accession contains comprehensive dataset and reports collected in support of the Mamala Bay Study during 1993-1995. Physical, chemical, biological, and...

  3. Comprehensive joint feedback control for standing by functional neuromuscular stimulation-a simulation study.

    Science.gov (United States)

    Nataraj, Raviraj; Audu, Musa L; Kirsch, Robert F; Triolo, Ronald J

    2010-12-01

    Previous investigations of feedback control of standing after spinal cord injury (SCI) using functional neuromuscular stimulation (FNS) have primarily targeted individual joints. This study assesses the potential efficacy of comprehensive (trunk, hips, knees, and ankles) joint feedback control against postural disturbances using a bipedal, 3-D computer model of SCI stance. Proportional-derivative feedback drove an artificial neural network trained to produce muscle excitation patterns consistent with maximal joint stiffness values achievable about neutral stance given typical SCI muscle properties. Feedback gains were optimized to minimize upper extremity (UE) loading required to stabilize against disturbances. Compared to the baseline case of maximum constant muscle excitations used clinically, the controller reduced UE loading by 55% in resisting external force perturbations and by 84% during simulated one-arm functional tasks. Performance was most sensitive to inaccurate measurements of ankle plantar/dorsiflexion position and hip ab/adduction velocity feedback. In conclusion, comprehensive joint feedback demonstrates potential to markedly improve FNS standing function. However, alternative control structures capable of effective performance with fewer sensor-based feedback parameters may better facilitate clinical usage.

  4. Comprehensive Joint Feedback Control for Standing by Functional Neuromuscular Stimulation – a Simulation Study

    Science.gov (United States)

    Nataraj, Raviraj; Audu, Musa L.; Kirsch, Robert F.; Triolo, Ronald J.

    2013-01-01

    Previous investigations of feedback control of standing after spinal cord injury (SCI) using functional neuromuscular stimulation (FNS) have primarily targeted individual joints. This study assesses the potential efficacy of comprehensive (trunk, hips, knees, and ankles) joint-feedback control against postural disturbances using a bipedal, three-dimensional computer model of SCI stance. Proportional-derivative feedback drove an artificial neural network trained to produce muscle excitation patterns consistent with maximal joint stiffness values achievable about neutral stance given typical SCI muscle properties. Feedback gains were optimized to minimize upper extremity (UE) loading required to stabilize against disturbances. Compared to the baseline case of maximum constant muscle excitations used clinically, the controller reduced UE loading by 55% in resisting external force perturbations and by 84% during simulated one-arm functional tasks. Performance was most sensitive to inaccurate measurements of ankle plantar/dorsiflexion position and hip ab/adduction velocity feedback. In conclusion, comprehensive joint-feedback demonstrates potential to markedly improve FNS standing function. However, alternative control structures capable of effective performance with fewer sensor-based feedback parameters may better facilitate clinical usage. PMID:20923741

  5. Developing a More Comprehensive SOA Governance Framework by Using a Comparative Study Approach

    Directory of Open Access Journals (Sweden)

    Fazilat Hojaji

    2014-02-01

    Full Text Available Many companies have adopted Service-Oriented Architecture (SOA as an approach to improve agility and increase performance of system development.However, deploying SOA has been encountered to some challenges and problems including difficulties in designing effective decision structures and building a SOA roadmap, lack of service funding and lack of consistent governance processes. Therefore, to address SOA challenges, organizations require a comprehensive and applicable SOA governance framework to implement management and control mechanisms. Study of existing SOA governance frameworks reveals that these frameworks are not expressive enough to cover all important elements of SOA governance and also, the y have very little discussions and clarifications regarding underpinning structures such as SOA processes and activities, governance procedures and measurement metrics. In this paper, in the process of proposing a new SOA governance framework, a set of important elements for a desired SOA governance framework is proposed. Based on these elements, a more comprehensive and expressive framework is developed based on governance structure of COBIT. It focuses on covering SOA governance elements and resolving the shortcomings of the existing frameworks and can delivers an appropriate solution to help enable effective SOA governance.

  6. Teachers’ Thoughts and Students’ Strategies : An empirical study on Swedish upper-secondary students’ andteachers’ perception on reading comprehension

    OpenAIRE

    Sibahi, Samir

    2017-01-01

    Previous studies have shown that explicit reading strategy teaching has positive effects on English second language (ESL) students’ reading comprehension. However, Swedish upper- secondary students’ attitudes towards English reading comprehension classes are relatively unknown. This study therefore has the objectives of finding out to what extent reading strategies are taught explicitly in upper-secondary schools in Sweden, and to investigate how students and teachers perceive reading compreh...

  7. GLOBAL CLIMATE MODEL:A COMPREHENSIVE TOOL IN CLIMATE CHANGE IMPACT STUDIES

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    Dharmaveer Singh

    2015-01-01

    Full Text Available There is growing concern, how and to what extent future changes in climate will affect human society and natural environments. Continuous emissions of Green House Gasses (GHGs at or above current rates will cause further warming. This, in turn, may modify global climate system during 21st century that very likely would have larger impacts than those observed during 20th century. At present, Global Climate Models (GCMs are only the most reliable tools available for studying behaviour of the climate system. This paper presents a comprehensive review of GCMs including their development and applications in climate change impacts studies. Following a discussion of the limitations of GCMs at regional and local scales, different approaches of downscaling are discussed in detail.

  8. Scalable total synthesis and comprehensive structure-activity relationship studies of the phytotoxin coronatine.

    Science.gov (United States)

    Littleson, Mairi M; Baker, Christopher M; Dalençon, Anne J; Frye, Elizabeth C; Jamieson, Craig; Kennedy, Alan R; Ling, Kenneth B; McLachlan, Matthew M; Montgomery, Mark G; Russell, Claire J; Watson, Allan J B

    2018-03-16

    Natural phytotoxins are valuable starting points for agrochemical design. Acting as a jasmonate agonist, coronatine represents an attractive herbicidal lead with novel mode of action, and has been an important synthetic target for agrochemical development. However, both restricted access to quantities of coronatine and a lack of a suitably scalable and flexible synthetic approach to its constituent natural product components, coronafacic and coronamic acids, has frustrated development of this target. Here, we report gram-scale production of coronafacic acid that allows a comprehensive structure-activity relationship study of this target. Biological assessment of a >120 member library combined with computational studies have revealed the key determinants of potency, rationalising hypotheses held for decades, and allowing future rational design of new herbicidal leads based on this template.

  9. Biomarkers of cancer cachexia.

    Science.gov (United States)

    Loumaye, Audrey; Thissen, Jean-Paul

    2017-12-01

    Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. However, early diagnosis of cancer cachexia is currently limited for several reasons. Indeed, cachexia development is variable according to tumor and host characteristics. In addition, safe, accessible and non-invasive tools to detect skeletal muscle atrophy are desperately lacking in clinical practice. Finally, the precise molecular mechanisms and the key players involved in cancer cachexia remain poorly characterized. The need for an early diagnosis of cancer cachexia supports therefore the quest for a biomarker that might reflect skeletal muscle atrophy process. Current research offers different promising ways to identify such a biomarker. Initially, the quest for a biomarker of cancer cachexia has mostly focused on mediators of muscle atrophy, produced by both tumor and host, in an attempt to define new therapeutic approaches. In another hand, molecules released by the muscle into the circulation during the atrophy process have been also considered as potential biomarkers. More recently, several "omics" studies are emerging to identify new muscular or circulating markers of cancer cachexia. Some genetic markers could also contribute to identify patients more susceptible to develop cachexia. This article reviews our current knowledge regarding potential biomarkers of cancer cachexia. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  10. A Comprehensive and Comparative Study of Wolfiporia extensa Cultivation Regions by Fourier Transform Infrared Spectroscopy and Ultra-Fast Liquid Chromatography

    Science.gov (United States)

    Li, Yan; Zhang, Ji; Li, Tao; Liu, Honggao

    2016-01-01

    Nowadays, Wolfiporia extensa as a popular raw material in food and medicine industry has received increasing interests. Due to supply shortage, this species of edible and medicinal mushroom has been cultivated in some provinces of China. In the present study, cultivated W. extensa collected from six regions in Yunnan Province of China were analyzed by an integrated method based on Fourier transform infrared (FT-IR) spectroscopy and ultra-fast liquid chromatography (UFLC) coupled with multivariate analysis including partial least squares discriminant analysis (PLS-DA) and hierarchical cluster analysis (HCA) in order to investigate the differences and similarities in different origins and parts. In the tested mushroom samples, characteristic FT-IR spectra were obtained for acquiring comprehensive fuzz chemical information and pachymic acid was determinated as a biomarker in the meantime. From the results, the comparison of samples was achieved successfully according to their geographical regions and different parts. All the samples displayed regional dependence and the inner parts showed better quality consistency. In addition, the chemical constituents of cultivated W. extensa could be also affected by the cultivation methods. Meanwhile, there was an interesting finding that the soil properties of cultivation regions may have a relationship with the chemical constituents of the epidermis of soil-cultured W. extensa, rather than the inner parts. Collectively, it demonstrated that the present study could provide comprehensive chemical evidence for the critical complement of quality evaluation on the cultivated W. extensa. Moreover, it may be available for the further researches of complicated mushrooms in practice. PMID:28036354

  11. A Comprehensive and Comparative Study of Wolfiporia extensa Cultivation Regions by Fourier Transform Infrared Spectroscopy and Ultra-Fast Liquid Chromatography.

    Directory of Open Access Journals (Sweden)

    Yan Li

    Full Text Available Nowadays, Wolfiporia extensa as a popular raw material in food and medicine industry has received increasing interests. Due to supply shortage, this species of edible and medicinal mushroom has been cultivated in some provinces of China. In the present study, cultivated W. extensa collected from six regions in Yunnan Province of China were analyzed by an integrated method based on Fourier transform infrared (FT-IR spectroscopy and ultra-fast liquid chromatography (UFLC coupled with multivariate analysis including partial least squares discriminant analysis (PLS-DA and hierarchical cluster analysis (HCA in order to investigate the differences and similarities in different origins and parts. In the tested mushroom samples, characteristic FT-IR spectra were obtained for acquiring comprehensive fuzz chemical information and pachymic acid was determinated as a biomarker in the meantime. From the results, the comparison of samples was achieved successfully according to their geographical regions and different parts. All the samples displayed regional dependence and the inner parts showed better quality consistency. In addition, the chemical constituents of cultivated W. extensa could be also affected by the cultivation methods. Meanwhile, there was an interesting finding that the soil properties of cultivation regions may have a relationship with the chemical constituents of the epidermis of soil-cultured W. extensa, rather than the inner parts. Collectively, it demonstrated that the present study could provide comprehensive chemical evidence for the critical complement of quality evaluation on the cultivated W. extensa. Moreover, it may be available for the further researches of complicated mushrooms in practice.

  12. Short-Term Exposure to Ambient Air Pollution and Biomarkers of Systemic Inflammation: The Framingham Heart Study.

    Science.gov (United States)

    Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H; Rice, Mary B; Ljungman, Petter L; Schwartz, Joel D; Coull, Brent A; Koutrakis, Petros; Gold, Diane R; Keaney, John F; Vasan, Ramachandran S; Benjamin, Emelia J; Mittleman, Murray A

    2017-09-01

    The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation cohorts in the greater Boston area. We included 3996 noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived within 50 km from a central air pollution monitoring site in Boston, MA, and calculated the 1- to 7-day moving averages of fine particulate matter (diameterpollution was associated with higher levels of C-reactive protein, interleukin-6, and tumor necrosis factor receptor 2 but not fibrinogen or tumor necrosis factor α in individuals residing in the greater Boston area. © 2017 American Heart Association, Inc.

  13. Assessing arsenic exposure from consumption of seafood from Vieques-Puerto Rico: a pilot biomonitoring study using different biomarkers.

    Science.gov (United States)

    Mansilla-Rivera, Imar; Nazario, Cruz M; Ramírez-Marrero, Farah A; Crespo, Carlos J; Rodríguez-Sierra, Carlos J

    2014-02-01

    The various toxic effects associated with inorganic arsenic (iAs) warrants that exposure sources be identified. This pilot study evaluated if greater seafood consumption from Vieques-Puerto Rico is associated with increased exposure to iAs. Nail, hair, and urine samples were used as biomarkers of iAs exposure in adult women and men from Vieques classified as high (n = 31) and low (n = 21) seafood consumers, who reported eating fish and/or shellfish ≥1 time per week and once per month or less, respectively. The sum of urinary iAs (As III + As V), monomethylarsonic acid (MA[V]), and dimethylarsinic acid (DMA[V]), denoted as SumAs, fluctuated from 3.3 µg/g Cr (1.2 μg/L) to 42.7 μg/g Cr (42 μg/L) (n = 52). Levels of As in nail samples (n = 49) varied from 0.04 to 0.82 μg/g dry weight (dw), whereas in hair (n = 49) As was only detected in 49 % of the samples with a maximum value of 0.95 μg/g dw. None of the biomarkers of exposure to As exceeded exposure reference values for urine (50 μg/g Cr or 50 μg/L), nails (1 μg/g), or hair (1 μg/g). However, median (10.0 μg/g Cr; 10.6 μg/L) and 95th percentile (31.9 μg/g Cr; 40.4 μg/L) of urinary SumAs were higher in Vieques samples than in the those from the general population of other countries. Among the three biomarkers of exposure, nail samples reflected better the exposure to iAs from seafood consumption with significantly higher average As concentrations in high (0.24 μg/g) than low (0.12 μg/g) seafood consumers. Multivariate results for As in nail samples (R(2) = 0.55, p < 0.0001) showed a positive association with fish consumption, particularly for men, with levels increasing with years of residency in Vieques.

  14. Associations between Urinary Excretion of Cadmium and Renal Biomarkers in Nonsmoking Females: A Cross-Sectional Study in Rural Areas of South China

    Directory of Open Access Journals (Sweden)

    Yun-rui Zhang

    2015-09-01

    Full Text Available Objectives: The aim of this study was to systematically evaluate the relationship between urinary excretion of cadmium (U-Cd and biomarkers of renal dysfunction. Methods: One hundred eighty five non-smoking female farmers (aged from 44 to 71 years were recruited from two rural areas with different cadmium levels of exposure in southern China. Morning spot urine samples were collected for detecting U-Cd, urinary creatinine (U-cre, β2-microglobulin (β2-MG, α1-microglobulin (α1-MG, metallothionein (MT, retinol binding protein (RBP, albumin (AB, N-acetyl-β-D-glucosaminidase (NAG, alkaline phosphatase (ALP, γ-glutamyl transpeptidase (GGT and kidney injury molecule-1 (KIM-1. Spearman’s rank correlation was carried out to assess pairwise bivariate associations between continuous variables. Three different models of multiple linear regression (the cre-corrected, un-corrected and cre-adjusted model were used to model the dose-response relationships between U-Cd and nine urine markers. Results: Spearman’s rank correlation showed that NAG, ALP, RBP, β2-MG and MT were significantly associated with U-Cd for both cre-corrected and observed data. Generally, NAG correlated best with U-Cd among the nine biomarkers studied, followed by ALP and MT. In the un-corrected model and cre-adjusted model, the regression coefficients and R2 of nine biomarkers were larger than the corresponding values in the cre-corrected model, indicating that the use of observed data was better for investigating the relationship between biomarkers and U-Cd than cre-corrected data. Conclusions: Our results suggest that NAG, MT and ALP in urine were better biomarkers for long-term environmental cadmium exposure assessment among the nine biomarkers studied. Further, data without normalization with creatinine show better relationships between cadmium exposure and renal dysfunction.

  15. A Prospective Open-label Pilot Study of Fluvastatin on Pro-inflammatory and Pro-thrombotic Biomarkers in Antiphospholipid Antibody Positive Patients

    Science.gov (United States)

    Erkan, Doruk; Willis, Rohan; Murthy, Vijaya L.; Basra, Gurjot; Vega, JoAnn; Ruiz Limón, Patricia; Carrera, Ana Laura; Papalardo, Elizabeth; Martínez-Martínez, Laura Aline; González, Emilio B.; Pierangeli, Silvia S.

    2014-01-01

    Objective: To determine if pro-inflammatory and pro-thrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. Methods: Four groups of patients (age 18-65) were recruited: a) Primary Antiphospholipid Syndrome (PAPS); b) Systemic Lupus Erythematosus (SLE) with APS (SLE/APS); c) Persistent aPL positivity without SLE or APS (Primary aPL); and d) Persistent aPL positivity with SLE but no APS (SLE/aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for three months. At three months, patients stopped the study medication and they were followed for another three months. Blood samples for 12 pro-inflammatory and pro-thrombotic biomarkers were collected monthly for six months. Results: Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75%) biomarkers (interleukin [IL]-6, IL1β, vascular endothelial growth factor [VEGF], tumor necrosis factor [TNF]-□α, interferon [IFN]-α, inducible protein-10 [IP10], soluble CD40 ligand [sCD40L], soluble tissue factor [sTF], and intracellular cellular adhesion molecule [ICAM]-1) were significantly elevated. Twenty-four patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50%) biomarkers (IL1β, VEGF, TNFα, IP10, sCD40L, and sTF). Conclusion: Our prospective mechanistic study demonstrates that pro-inflammatory and pro-thrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients. PMID:23933625

  16. The potential biomarkers in predicting pathologic response of breast cancer to three different chemotherapy regimens: a case control study

    Directory of Open Access Journals (Sweden)

    Xu Chaoyang

    2009-07-01

    Full Text Available Abstract Background Preoperative chemotherapy (PCT has become the standard of care in locally advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to therapy would help optimize treatment, improve treatment outcomes, and avoid unnecessary exposure to potential toxicities. This study is to determine whether selected biomarkers could predict pathologic response (PR of breast tumors to three different PCT regimens, and to identify a subset of patients who would benefit from a given type of treatment. Methods 118 patients with primary breast tumor were identified and three PCT regimens including DEC (docetaxel+epirubicin+cyclophosphamide, VFC (vinorelbine/vincristine+5-fluorouracil+cyclophosphamide and EFC (epirubicin+5-fluorouracil+cyclophosphamide were investigated. Expression of steroid receptors, HER2, P-gp, MRP, GST-pi and Topo-II was evaluated by immunohistochemical scoring on tumor tissues obtained before and after PCT. The PR of breast carcinoma was graded according to Sataloff's classification. Chi square test, logistic regression and Cochran-Mantel-Haenszel assay were performed to determine the association between biomarkers and PR, as well as the effectiveness of each regimen on induction of PR. Results There was a clear-cut correlation between the expression of ER and decreased PR to PCT in all three different regimens (p p Conclusion ER is an independent predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary breast tumors, while HER2 is only predictive for DEC regimen. Expression of PgR, Topo-II, P-gp, MRP and GST-pi are not predictive for PR to any PCT regimens investigated. Results obtained in this clinical study may be helpful for the selection of appropriate treatments for breast cancer patients.

  17. Hair cortisol as a hypothalamic-pituitary-adrenal axis biomarker in pregnant women with asthma: a retrospective observational study.

    Science.gov (United States)

    Smy, Laura; Shaw, Kaitlyn; Amstutz, Ursula; Smith, Anne; Berger, Howard; Carleton, Bruce; Koren, Gideon

    2016-07-20

    Cortisol is a hormone involved in many physiological functions including fetal maturation and epigenetic programming during pregnancy. This study aimed to use hair cortisol as a biomarker of chronic inhaled corticosteroid (ICS) exposure and assess the potential effects of asthma on the hypothalamic-pituitary-adrenal (HPA) axis in pregnant women. We hypothesized that pregnant women with asthma treated with ICS would exhibit lower hair cortisol concentrations, indicative of adrenal suppression, compared to women with asthma not using ICS and women who do not have asthma. We performed an observational retrospective cohort study. Hair samples were analyzed from pregnant women with asthma, with (n = 56) and without (n = 31) ICS treatment, and pregnant women without asthma (n = 31). Hair samples were segmented based on the growth rate of 1 cm/month and analyzed by enzyme immunoassay to provide cortisol concentrations corresponding to preconception, trimesters 1-3, and postpartum. Hair cortisol concentrations were compared within and among the groups using non-parametric statistical tests. Hair cortisol concentrations increased across trimesters for all three groups, but this increase was dampened in women with asthma (P = 0.03 for Controls vs. ICS Treated and Controls vs. No ICS). ICS Treated women taking more than five doses per week had hair cortisol concentrations 47 % lower in third trimester than Controls. Linear regression of the third trimester hair cortisol results identified asthma as a significant factor when comparing consistent ICS use or asthma as the predictor (F(1, 25) = 9.7, P = 0.005, R(2) adj = 0.257). Hair cortisol successfully showed the expected change in cortisol over the course of pregnancy and may be a useful biomarker of HPA axis function in pregnant women with asthma. The potential impact of decreased maternal cortisol in women with asthma on perinatal outcomes remains to be determined.

  18. Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study

    Directory of Open Access Journals (Sweden)

    Andreas eDix

    2015-03-01

    Full Text Available Sepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to classify if a sample contains a bacterial, fungal, or mock-infection. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97% for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83% for an additional test dataset comprising Cryptococcus neoformans infections. Furthermore, the classifier is robust to Gaussian noise, indicating correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances.

  19. Biomarkers for Detecting Mitochondrial Disorders

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2018-01-01

    Full Text Available (1 Objectives: Mitochondrial disorders (MIDs are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and late stages. This is why there is a need to provide biomarkers, which can be easily obtained in the case of suspecting a MID to initiate the further diagnostic work-up. (2 Methods: Literature review. (3 Results: Biomarkers for diagnostic purposes are used to confirm a suspected diagnosis and to facilitate and speed up the diagnostic work-up. For diagnosing MIDs, a number of dry and wet biomarkers have been proposed. Dry biomarkers for MIDs include the history and clinical neurological exam and structural and functional imaging studies of the brain, muscle, or myocardium by ultrasound, computed tomography (CT, magnetic resonance imaging (MRI, MR-spectroscopy (MRS, positron emission tomography (PET, or functional MRI. Wet biomarkers from blood, urine, saliva, or cerebrospinal fluid (CSF for diagnosing MIDs include lactate, creatine-kinase, pyruvate, organic acids, amino acids, carnitines, oxidative stress markers, and circulating cytokines. The role of microRNAs, cutaneous respirometry, biopsy, exercise tests, and small molecule reporters as possible biomarkers is unsolved. (4 Conclusions: The disadvantages of most putative biomarkers for MIDs are that they hardly meet the criteria for being acceptable as a biomarker (missing longitudinal studies, not validated, not easily feasible, not cheap, not ubiquitously available and that not all MIDs manifest in the brain, muscle, or myocardium. There is currently a lack of validated biomarkers for diagnosing MIDs.

  20. A comprehensive study of extended tetrathiafulvalene cruciform molecules for molecular electronics: synthesis and electrical transport measurements.

    Science.gov (United States)

    Parker, Christian R; Leary, Edmund; Frisenda, Riccardo; Wei, Zhongming; Jennum, Karsten S; Glibstrup, Emil; Abrahamsen, Peter Bæch; Santella, Marco; Christensen, Mikkel A; Della Pia, Eduardo Antonio; Li, Tao; Gonzalez, Maria Teresa; Jiang, Xingbin; Morsing, Thorbjørn J; Rubio-Bollinger, Gabino; Laursen, Bo W; Nørgaard, Kasper; van der Zant, Herre; Agrait, Nicolas; Nielsen, Mogens Brøndsted

    2014-11-26

    Cruciform-like molecules with two orthogonally placed π-conjugated systems have in recent years attracted significant interest for their potential use as molecular wires in molecular electronics. Here we present synthetic protocols for a large selection of cruciform molecules based on oligo(phenyleneethynylene) (OPE) and tetrathiafulvalene (TTF) scaffolds, end-capped with acetyl-protected thiolates as electrode anchoring groups. The molecules were subjected to a comprehensive study of their conducting properties as well as their photophysical and electrochemical properties in solution. The complex nature of the molecules and their possible binding in different configurations in junctions called for different techniques of conductance measurements: (1) conducting-probe atomic force microscopy (CP-AFM) measurements on self-assembled monolayers (SAMs), (2) mechanically controlled break-junction (MCBJ) measurements, and (3) scanning tunneling microscopy break-junction (STM-BJ) measurements. The CP-AFM measurements showed structure-property relationships from SAMs of series of OPE3 and OPE5 cruciform molecules; the conductance of the SAM increased with the number of dithiafulvene (DTF) units (0, 1, 2) along the wire, and it increased when substituting two arylethynyl end groups of the OPE3 backbone with two DTF units. The MCBJ and STM-BJ studies on single molecules both showed that DTFs decreased the junction formation probability, but, in contrast, no significant influence on the single-molecule conductance was observed. We suggest that the origins of the difference between SAM and single-molecule measurements lie in the nature of the molecule-electrode interface as well as in effects arising from molecular packing in the SAMs. This comprehensive study shows that for complex molecules care should be taken when directly comparing single-molecule measurements and measurements of SAMs and solid-state devices thereof.

  1. A comprehensive study of metal distribution in three main classes of seaweed

    International Nuclear Information System (INIS)

    Ryan, Siobhan; McLoughlin, Peter; O'Donovan, Orla

    2012-01-01

    This paper provides one of the most comprehensive studies of metal distributions in three main macroalgae species. In this novel study, levels of total, intracellular and surface bound Pb, Zn, As, Cd, Co, Cr, Cu, Mn and Ni associated with Polysiphonia lanosa (L) Tandy, Ascophyllum nodosum (L) Le Jolis, Fucus vesiculosus (L) and Ulva sp. were determined. Additionally, water and sediment metal levels were analysed to gain an insight into the relative uptake efficiencies of different macroalgal species. Samples were collected from a clean site in Fethard-on-Sea, Wexford, Ireland (52°11′53.68′N, 6°49′34.64′W), in May 2008. Results demonstrated that total, intracellular and surface bound metal levels varied according to metal and seaweed species, with the highest proportion of metals found to be intracellular. Inhibition of Mn uptake by Zn was indicated for P. lanosa. Furthermore, P. lanosa had enhanced bioaccumulation ability, with the highest Concentration Factor reported of any seaweed to date. - Highlights: ► Three main classes of seaweed were collected from the South-East coast of Ireland. ► Metal levels (total, intracellular and surface-bound) in four seaweed species were determined. ► Metal levels of seawater and sediment samples collected from the same location were quantified. ► The Concentration Factors for P. lanosa, A. nodosum, F. vesiculosus and Ulva sp., were calculated. ► Interspecies variations in seaweed metal concentrations were demonstrated. - This study, reports the most comprehensive uptake efficiencies and distributions of metals in four main seaweed sps., with P. lanosa demonstrating excellent bioaccumulation ability.

  2. Evaluation of flavonoids and enterolactone in overnight urine as intake biomarkers of fruits, vegetables and beverages in the Inter99 cohort study using the method of triads

    DEFF Research Database (Denmark)

    Krogholm, Kirstine Suszkiewicz; Bysted, Anette; Brantsaeter, A. L.

    2012-01-01

    in 24 h urine as an alternative and more feasible biomarker of fruit, vegetable and beverage intake. A total of 191 individuals in the Inter99 cohort in Denmark completed the validation study. Concentrations of nine urinary flavonoid aglycones (quercetin, isorhamnetin, tamarixetin, kaempferol......, hesperetin, naringenin, eriodictyol, phloretin and apigenin) and enterolactone were determined in overnight and 24 h urine samples, and their validity as biomarkers of fruit, vegetable and beverage intake was evaluated in relation to two independent reference methods (Inter99 FFQ data and plasma carotenoids...

  3. Application, results and perceptions of a think-aloud study in listening comprehension of Spanish

    DEFF Research Database (Denmark)

    Nogueroles López, Marta

    2017-01-01

    . After listening, they completed five comprehension questions, listened one more time with the transcript, reflected on their understanding and their strategic behaviour, and evaluated the protocol itself. These interviews were recorded, transcribed, analysed, categorized and computed. Results reveal......The present article outlines the procedure and shows the outcomes of a think-aloud study intended to, first, find out what listening strategies Hong Kong students of Spanish use to comprehend a particular oral passage in the target language, and, second, understand the participants’ perceptions...... of the think-aloud protocol. Such a protocol was developed during interviews in which students listened to an unidirectional text in Spanish twice, the first time interruptedly and the second without intermediate pauses, and were asked to verbalize the processes they had been using to understand such a passage...

  4. Using interactive graphical and technological strategies for EFL reading comprehension: A case study involving engineering students

    Directory of Open Access Journals (Sweden)

    Julia Valeska Barraza

    2014-09-01

    Full Text Available This qualitative study engaged a group of engineering students in the use of interactive graphical and technological strategies called IGOs (interactive, graphic organisers software in order to improve their level of EFL reading comprehension. The learners were asked to use three different types of IGOs, causes and effects, a sequence of events and pros and cons. Data was gathered through an opinion’s survey with the intention of collecting and evaluating the students’ perceptions on the use of the IGOs software. Findings revealed that most of the learners answered positively. Students also expressed they wanted more opportunities to use this software; because they not only could improve their scores but also, they enjoyed the experience they had using the new strategies software.

  5. Comprehensive study of temperature anomalies on of the former Semipalatinsk nuclear test site territory

    International Nuclear Information System (INIS)

    Subbotin, S.B.; Lukashenko, S.N.; Dmitropavlenko, V.N.; Ajdarkhanov, A.O.; Duchkov, A.D.; Kazantsev, S.A.

    2005-01-01

    In 1997 by the space images data in the Semipalatinsk test site area a mysterious anomaly thermal zone with square about 20 thousand sq. km. with soil temperature 10-15 degrees above than on the adjacent areas was found. The results of 1996-1999 observation confirm the presence of steady temperature anomalies. A number of scientists are suggesting that the increased temperature zones are related with conducted nuclear tests. These temperature anomalies related with objects of nuclear explosions conduction and its have limited distribution the spatially attached to nuclear explosions cavities. Anomalies are the sequent of residual manifestation of long-time geothermal activity in the underground nuclear explosions epicenters. In 2001 in the frameworks of joint program 'Comprehensive study of thermal anomalies on the territory of the former Semipalatinsk test site' the direct measurements of soils on the five sections which were selected by the results of space images

  6. Comprehensive genomic studies: emerging regulatory, strategic, and quality assurance challenges for biorepositories.

    Science.gov (United States)

    McDonald, Sandra A; Mardis, Elaine R; Ota, David; Watson, Mark A; Pfeifer, John D; Green, Jonathan M

    2012-07-01

    As part of the molecular revolution sweeping medicine, comprehensive genomic studies are adding powerful dimensions to medical research. However, their power exposes new regulatory, strategic, and quality assurance challenges for biorepositories. A key issue is that unlike other research techniques commonly applied to banked specimens, nucleic acid sequencing, if sufficiently extensive, yields data that could identify a patient. This evolving paradigm renders the concepts of anonymized and anonymous specimens increasingly outdated. The challenges for biorepositories in this new era include refined consent processes and wording, selection and use of legacy specimens, quality assurance procedures, institutional documentation, data sharing, and interaction with institutional review boards. Given current trends, biorepositories should consider these issues now, even if they are not currently experiencing sample requests for genomic analysis. We summarize our current experiences and best practices at Washington University Medical School, St Louis, MO, our perceptions of emerging trends, and recommendations.

  7. A Comprehensive Study of the Polypropylene Fiber Reinforced Fly Ash Based Geopolymer

    DEFF Research Database (Denmark)

    Ranjbar, Navid; Mehrali, Mehdi; Behnia, Arash

    2016-01-01

    and long term impacts of different volume percentages of polypropylene fiber (PPF) reinforcement on fly ash based geopolymer composites. Different characteristics of the composite were compared at fresh state by flow measurement and hardened state by variation of shrinkage over time to assess the response...... of composites under flexural and compressive load conditions. The fiber-matrix interface, fiber surface and toughening mechanisms were assessed using field emission scan electron microscopy (FESEM) and atomic force microscopy (AFM). The results show that incorporation of PPF up to 3 wt % into the geopolymer......As a cementitious material, geopolymers show a high quasi-brittle behavior and a relatively low fracture energy. To overcome such a weakness, incorporation of fibers to a brittle matrix is a well-known technique to enhance the flexural properties. This study comprehensively evaluates the short...

  8. Pulmonary function and CT biomarkers as risk factors for cardiovascular events in male lung cancer screening participants: the NELSON study

    Energy Technology Data Exchange (ETDEWEB)

    Takx, Richard A.P.; Hoesein, Firdaus A.A.M.; Mali, Willem P.T.M.; Leiner, Tim; Jong, Pim A. de [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Vliegenthart, Rozemarijn [University of Groningen, University Medical Center Groningen, Center for Medical Imaging - North East Netherlands, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, Department of Radiology, Groningen (Netherlands); Isgum, Ivana [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Koning, Harry J. de; Aalst, Carlijn M. van der [Erasmus Medical Center Rotterdam, Department of Public Health, Rotterdam (Netherlands); Zanen, Pieter; Lammers, Jan-Willem J. [University Medical Center Utrecht, Department of Pulmonology, Utrecht (Netherlands); Groen, Harry J.M. [University Medical Center Groningen, Department of Pulmonology, Groningen (Netherlands); Rikxoort, Eva M. van; Ginneken, Bram van [Radboud University Nijmegen Medical Centre, Department of Radiology, Nijmegen (Netherlands); Institute for Medical Image Computing, Fraunhofer MEVIS, Bremen (Germany); Schmidt, Michael [Institute for Medical Image Computing, Fraunhofer MEVIS, Bremen (Germany); Oudkerk, Matthijs [University of Groningen, University Medical Center Groningen, Center for Medical Imaging - North East Netherlands, Groningen (Netherlands)

    2015-01-15

    The objective of this study was to investigate the association of spirometry and pulmonary CT biomarkers with cardiovascular events. In this lung cancer screening trial 3,080 male participants without a prior cardiovascular event were analysed. Fatal and non-fatal cardiovascular events were included. Spirometry included forced expiratory volume measured in units of one-second percent predicted (FEV{sub 1}%predicted) and FEV{sub 1} divided by forced vital capacity (FVC; FEV{sub 1}/FVC). CT examinations were quantified for coronary artery calcium volume, pulmonary emphysema (perc15) and bronchial wall thickness (pi10). Data were analysed via a Cox proportional hazard analysis, net reclassification improvement (NRI) and C-indices. 184 participants experienced a cardiovascular event during a median follow-up of 2.9 years. Age, pack-years and smoking status adjusted hazard ratios were 0.992 (95 % confidence interval (CI) 0.985-0.999) for FEV{sub 1}%predicted, 1.000 (95%CI 0.986-1.015) for FEV{sub 1}/FVC, 1.014 (95%CI 1.005-1.023) for perc15 per 10 HU, and 1.269 (95%CI 1.024-1.573) for pi10 per 1 mm. The incremental C-index (<0.015) and NRI (<2.8 %) were minimal. Coronary artery calcium volume had a hazard ratio of 1.046 (95%CI 1.034-1.058) per 100 mm{sup 3}, an increase in C-index of 0.076 and an NRI of 16.9 % (P < 0.0001). Pulmonary CT biomarkers and spirometry measurements were significantly associated with cardiovascular events, but did not contain clinically relevant independent prognostic information for cardiovascular events. (orig.)

  9. Effects of adenotonsillectomy on plasma inflammatory biomarkers in obese children with obstructive sleep apnea: A community-based study.

    Science.gov (United States)

    Kheirandish-Gozal, L; Gileles-Hillel, A; Alonso-Álvarez, M L; Peris, E; Bhattacharjee, R; Terán-Santos, J; Duran-Cantolla, J; Gozal, D

    2015-07-01

    Obesity and obstructive sleep apnea syndrome (OSA) are highly prevalent and frequently overlapping conditions in children that lead to systemic inflammation, the latter being implicated in the various end-organ morbidities associated with these conditions. To examine the effects of adenotonsillectomy (T&A) on plasma levels of inflammatory markers in obese children with polysomnographically diagnosed OSA who were prospectively recruited from the community. Obese children prospectively diagnosed with OSA, underwent T&A and a second overnight polysomnogram (PSG) after surgery. Plasma fasting morning samples obtained after each of the two PSGs were assayed for multiple inflammatory and metabolic markers including interleukin (IL)-6, IL-18, plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), adiponectin, apelin C, leptin and osteocrin. Out of 122 potential candidates, 100 obese children with OSA completed the study with only one-third exhibiting normalization of their PSG after T&A (that is, apnea-hypopnea index (AHI) ≤1/hour total sleep time). However, overall significant decreases in MCP-1, PAI-1, MMP-9, IL-18 and IL-6, and increases in adropin and osteocrin plasma concentrations occurred after T&A. Several of the T&A-responsive biomarkers exhibited excellent sensitivity and moderate specificity to predict residual OSA (that is, AHI⩾5/hTST). A defined subset of systemic inflammatory and metabolic biomarkers is reversibly altered in the context of OSA among community-based obese children, further reinforcing the concept on the interactive pro-inflammatory effects of sleep disorders such as OSA and obesity contributing to downstream end-organ morbidities.

  10. Integrated preservation and sample clean up procedures for studying water ingestion by recreational swimmers via urinary biomarker determination.

    Science.gov (United States)

    Cantú, Ricardo; Shoemaker, Jody A; Kelty, Catherine A; Wymer, Larry J; Behymer, Thomas D; Dufour, Alfred P; Magnuson, Matthew L

    2017-08-22

    The use of cyanuric acid as a biomarker for ingestion of swimming pool water may lead to quantitative knowledge of the volume of water ingested during swimming, contributing to a better understanding of disease resulting from ingestion of environmental contaminants. When swimming pool water containing chlorinated cyanurates is inadvertently ingested, cyanuric acid is excreted quantitatively within 24 h as a urinary biomarker of ingestion. Because the volume of water ingested can be quantitatively estimated by calculation from the concentration of cyanuric acid in 24 h urine samples, a procedure for preservation, cleanup, and analysis of cyanuric acid was developed to meet the logistical demands of large scale studies. From a practical stand point, urine collected from swimmers cannot be analyzed immediately, given requirements of sample collection, shipping, handling, etc. Thus, to maintain quality control to allow confidence in the results, it is necessary to preserve the samples in a manner that ensures as quantitative analysis as possible. The preservation and clean-up of cyanuric acid in urine is complicated because typical approaches often are incompatible with the keto-enol tautomerization of cyanuric acid, interfering with cyanuric acid sample preparation, chromatography, and detection. Therefore, this paper presents a novel integration of sample preservation, clean-up, chromatography, and detection to determine cyanuric acid in 24 h urine samples. Fortification of urine with cyanuric acid (0.3-3.0 mg/L) demonstrated accuracy (86-93% recovery) and high reproducibility (RSD urine suggested sufficient cyanuric acid stability for sample collection procedures, while longer holding times suggested instability of the unpreserved urine. Preserved urine exhibited a loss of around 0.5% after 22 days at refrigerated storage conditions of 4 °C. Published by Elsevier B.V.

  11. Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers.

    Science.gov (United States)

    Duscharla, Divya; Bhumireddy, Sudarshana Reddy; Lakshetti, Sridhar; Pospisil, Heike; Murthy, P V L N; Walther, Reinhard; Sripadi, Prabhakar; Ummanni, Ramesh

    2016-01-01

    Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient's serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet's serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10-6 in Fischer's exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis.

  12. Subtypes of depressive symptoms and inflammatory biomarkers: An exploratory study on a sample of HIV-positive patients.

    Science.gov (United States)

    Norcini Pala, A; Steca, P; Bagrodia, R; Helpman, L; Colangeli, V; Viale, P; Wainberg, M L

    2016-08-01

    Depressive symptoms cause major impairment and may accelerate HIV progression despite the use of antiretroviral medication. The somatic symptoms criteria for HIV infection and depression partially overlap, which can make differential diagnosis challenging. Because of chronic inflammation caused by HIV infection, HIV-positive patients may develop somatic and affective-cognitive symptoms of depression. Inflammation-related depression is primarily characterized with severe somatic symptoms such as fatigue and sleep disturbance. This study sought to explore the patterns of somatic and cognitive-affective depressive symptoms that characterize HIV-positive patients. Our specific aims were (1) to identify subtypes of depressive symptoms in a sample of HIV-positive patients; and (2) to test the subtypes' difference on inflammatory and HIV disease progression biomarkers. HIV-positive men and women (N=102) with and without depressive symptoms were randomly selected from an Italian HIV clinic. Depressive symptoms (PHQ-9), viral load (VL), CD4+, Il-6, TNF-α, and monocytes were assessed. The three subtypes formed using Latent Class Analysis (LCA) identified patients with (1) severe cognitive-affective and somatic depressive symptoms; (2) severe/moderate somatic symptoms; and (3) absent or low depressive symptoms. The subtype with severe/moderate somatic symptoms was characterized with elevated levels of Il-6 and monocytes. No difference on HIV progression biomarkers was found. The subtypes of depressive symptoms might help differentiating depressive symptoms from HIV- and inflammatory-related somatic symptoms. When present, cognitive-affective and/or somatic symptoms cause significant impairment to patients' lives and thus warrant further assessment and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Cognitive Frailty in China: Results from China Comprehensive Geriatric Assessment Study

    Directory of Open Access Journals (Sweden)

    Lina Ma

    2017-10-01

    Full Text Available ObjectiveCognitive frailty (CF refers to the co-occurrence of physical frailty (PF and cognitive impairment in persons without dementia. We aimed to explore the prevalence and associated factors of CF in China.MethodData were obtained from the China Comprehensive Geriatric Assessment Study. A total of 5,708 community-dwelling older adults without dementia were included. CF was assessed using the Mini–Mental State Examination for the evaluation of cognitive status and the Comprehensive Geriatric Assessment-Frailty Index for the evaluation of PF. Participants with both cognitive impairment and PF were classified as having CF. Sociodemographic and clinical history was also collected. Logistic analysis was used to explore the association between the associated factors and CF.ResultsThe overall crude prevalence of CF was 3.3% [95% confidence interval (CI = 3.0–4.0], and the standard prevalence of CF was 2.7% (95% CI = 2.0–3.0. The prevalence of CF was significantly higher in women than men and higher in residents of rural areas than urban areas. Moreover, the prevalence of CF was found to increase with age. Multiple factor analysis showed that depression (OR = 2.462, 95% CI = 1.066–5.687 and hearing impairment (OR = 2.713, 95% CI = 1.114–6.608 were independent associated factors of CF in elderly individuals with PF.ConclusionOur results provide the first empirical evidence of CF in China. We have identified several associated factors with CF which should be considered while assessing older adults. More studies in Chinese population with CF are demanded to confirm with our findings.

  14. A Comprehensive Study of Agricultural Drought Resistance and Background Drought Levels in Five Main Grain-Producing Regions of China

    OpenAIRE

    Lei Kang; Hongqi Zhang

    2016-01-01

    Drought control and resistance affect national food security. With this in mind, we studied five main grain-producing regions of China: Sanjiang Plain, Songnen Plain, Huang-Huai-Hai Plain, the middle Yangtze River and Jianghuai region and Sichuan Basin. Using GIS technology, we evaluated the comprehensive agricultural drought situation based on major crops, the basic drought resistance by integrating multiple indicators and the comprehensive drought resistance against background agricultural ...

  15. A study of a possible early reindeer domestication site on the Iamal peninsula (Russia) using geoarchaeological methods and lipid biomarkers.

    Science.gov (United States)

    Harrault, Loic; Milek, Karen; Dawson, Lorna; Anderson, David

    2016-04-01

    investigated to link these activities with past cultural layers. The first results from the lipid analysis show the presence of faecal material in three buried soil horizons. The chemical profiles of these samples differ with their locations: i) the sample located very close to the human settlement has a human profile while, ii) the two samples located farther from the settlements have an animal profile. Apart reindeer, this area contains few other animals and especially no others which congregate together in large numbers, therefore the animal faecal material found could come from reindeer. These results suggest that reindeer were present near this human archaeological site, which confirms the hypothesis of past herding activity. The next stage of this research is to integrate these results with other biomarkers and geoarchaeological methods. This study shows the potential of lipid biomarkers preserved in soils to better understand past human-animal interactions.

  16. Reading Comprehension and Working Memory's Executive Processes: An Intervention Study in Primary School Students

    Science.gov (United States)

    Garcia-Madruga, Juan A.; Elosua, Maria Rosa; Gil, Laura; Gomez-Veiga, Isabel; Vila, Jose Oscar; Orjales, Isabel; Contreras, Antonio; Rodriguez, Raquel; Melero, Maria Angeles; Duque, Gonzalo

    2013-01-01

    Reading comprehension is a highly demanding task that involves the simultaneous process of extracting and constructing meaning in which working memory's executive processes play a crucial role. In this article, a training program on working memory's executive processes to improve reading comprehension is presented and empirically tested in two…

  17. Ambient Air Pollution and Biomarkers of Health Effect.

    Science.gov (United States)

    Yang, Di; Yang, Xuan; Deng, Furong; Guo, Xinbiao

    2017-01-01

    Recently, the air pollution situation of our country is very serious along with the development of urbanization and industrialization. Studies indicate that the exposure of air pollution can cause a rise of incidence and mortality of many diseases, such as chronic obstructive pulmonary disease (COPD), asthma, myocardial infarction, and so on. However, there is now growing evidence showing that significant air pollution exposures are associated with early biomarkers in various systems of the body. In order to better prevent and control the damage effect of air pollution, this article summarizes comprehensively epidemiological studies about the bad effects on the biomarkers of respiratory system, cardiovascular system, and genetic and epigenetic system exposure to ambient air pollution.

  18. Broca's area, sentence comprehension, and working memory: an fMRI study

    Directory of Open Access Journals (Sweden)

    Corianne Rogalsky

    2008-10-01

    Full Text Available The role of Broca's area in sentence processing remains controversial. According to one view, Broca's area is involved in processing a subcomponent of syntactic processing. Another view holds that it contributes to sentence processing via verbal working memory. Sub-regions of Broca's area have been identified that are more active during the processing of complex (object-relative clause sentences compared to simple (subject-relative clause sentences. The present study aimed to determine if this complexity effect can be accounted for in terms of the articulatory rehearsal component of verbal working memory.  In a behavioral experiment, subjects were asked to comprehend sentences during concurrent speech articulation which minimizes articulatory rehearsal as a resource for sentence comprehension. A finger-tapping task was used as a control concurrent task. Only the object-relative clause sentences were more difficult to comprehend during speech articulation than during the manual task, showing that articulatory rehearsal does contribute to sentence processing.  A second experiment used fMRI to document the brain regions underlying this effect.  Subjects judged the plausibility of sentences during speech articulation, a finger-tapping task, or without a concurrent task. In the absence of a secondary task, Broca's area (pars triangularis and pars opercularis demonstrated an increase in activity as a function of syntactic complexity. However, during concurrent speech articulation (but not finger-tapping this complexity effect was eliminated in the pars opercularis suggesting that this region supports sentence comprehension via its role in articulatory rehearsal.  Activity in the pars triangularis was modulated by the finger-tapping task, but not the speech articulation task.

  19. Approximations to the distribution of a test statistic in covariance structure analysis: A comprehensive study.

    Science.gov (United States)

    Wu, Hao

    2018-05-01

    In structural equation modelling (SEM), a robust adjustment to the test statistic or to its reference distribution is needed when its null distribution deviates from a χ 2 distribution, which usually arises when data do not follow a multivariate normal distribution. Unfortunately, existing studies on this issue typically focus on only a few methods and neglect the majority of alternative methods in statistics. Existing simulation studies typically consider only non-normal distributions of data that either satisfy asymptotic robustness or lead to an asymptotic scaled χ 2 distribution. In this work we conduct a comprehensive study that involves both typical methods in SEM and less well-known methods from the statistics literature. We also propose the use of several novel non-normal data distributions that are qualitatively different from the non-normal distributions widely used in existing studies. We found that several under-studied methods give the best performance under specific conditions, but the Satorra-Bentler method remains the most viable method for most situations. © 2017 The British Psychological Society.

  20. Profiling biomarkers of traumatic axonal injury: From mouse to man.

    Science.gov (United States)

    Manivannan, Susruta; Makwana, Milan; Ahmed, Aminul Islam; Zaben, Malik

    2018-05-18

    Traumatic brain injury (TBI) poses a major public health problem on a global scale. Its burden results from high mortality and significant morbidity in survivors. This stems, in part, from an ongoing inadequacy in diagnostic and prognostic indicators despite significant technological advances. Traumatic axonal injury (TAI) is a key driver of the ongoing pathological process following TBI, causing chronic neurological deficits and disability. The science underpinning biomarkers of TAI has been a subject of many reviews in recent literature. However, in this review we provide a comprehensive account of biomarkers from animal models to clinical studies, bridging the gap between experimental science and clinical medicine. We have discussed pathogenesis, temporal kinetics, relationships to neuro-imaging, and, most importantly, clinical applicability in order to provide a holistic perspective of how this could improve TBI diagnosis and predict clinical outcome in a real-life setting. We conclude that early and reliable identification of axonal injury post-TBI with the help of body fluid biomarkers could enhance current care of TBI patients by (i) increasing speed and accuracy of diagnosis, (ii) providing invaluable prognostic information, (iii) allow efficient allocation of rehabilitation services, and (iv) provide potential therapeutic targets. The optimal model for assessing TAI is likely to involve multiple components, including several blood biomarkers and neuro-imaging modalities, at different time points. Copyright © 2018. Published by Elsevier B.V.

  1. Harvard Aging Brain Study : Dataset and accessibility

    NARCIS (Netherlands)

    Dagley, Alexander; LaPoint, Molly; Huijbers, Willem; Hedden, Trey; McLaren, Donald G.; Chatwal, Jasmeer P.; Papp, Kathryn V.; Amariglio, Rebecca E.; Blacker, Deborah; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Schultz, Aaron P.

    2017-01-01

    The Harvard Aging Brain Study is sharing its data with the global research community. The longitudinal dataset consists of a 284-subject cohort with the following modalities acquired: demographics, clinical assessment, comprehensive neuropsychological testing, clinical biomarkers, and neuroimaging.

  2. International benchmarking of specialty hospitals. A series of case studies on comprehensive cancer centres

    Science.gov (United States)

    2010-01-01

    Background Benchmarking is one of the methods used in business that is applied to hospitals to improve the management of their operations. International comparison between hospitals can explain performance differences. As there is a trend towards specialization of hospitals, this study examines the benchmarking process and the success factors of benchmarking in international specialized cancer centres. Methods Three independent international benchmarking studies on operations management in cancer centres were conducted. The first study included three comprehensive cancer centres (CCC), three chemotherapy day units (CDU) were involved in the second study and four radiotherapy departments were included in the final study. Per multiple case study a research protocol was used to structure the benchmarking process. After reviewing the multiple case studies, the resulting description was used to study the research objectives. Results We adapted and evaluated existing benchmarking processes through formalizing stakeholder involvement and verifying the comparability of the partners. We also devised a framework to structure the indicators to produce a coherent indicator set and better improvement suggestions. Evaluating the feasibility of benchmarking as a tool to improve hospital processes led to mixed results. Case study 1 resulted in general recommendations for the organizations involved. In case study 2, the combination of benchmarking and lean management led in one CDU to a 24% increase in bed utilization and a 12% increase in productivity. Three radiotherapy departments of case study 3, were considering implementing the recommendations. Additionally, success factors, such as a well-defined and small project scope, partner selection based on clear criteria, stakeholder involvement, simple and well-structured indicators, analysis of both the process and its results and, adapt the identified better working methods to the own setting, were found. Conclusions The improved

  3. Decreasing scoring errors on Wechsler Scale Vocabulary, Comprehension, and Similarities subtests: a preliminary study.

    Science.gov (United States)

    Linger, Michele L; Ray, Glen E; Zachar, Peter; Underhill, Andrea T; LoBello, Steven G

    2007-10-01

    Studies of graduate students learning to administer the Wechsler scales have generally shown that training is not associated with the development of scoring proficiency. Many studies report on the reduction of aggregated administration and scoring errors, a strategy that does not highlight the reduction of errors on subtests identified as most prone to error. This study evaluated the development of scoring proficiency specifically on the Wechsler (WISC-IV and WAIS-III) Vocabulary, Comprehension, and Similarities subtests during training by comparing a set of 'early test administrations' to 'later test administrations.' Twelve graduate students enrolled in an intelligence-testing course participated in the study. Scoring errors (e.g., incorrect point assignment) were evaluated on the students' actual practice administration test protocols. Errors on all three subtests declined significantly when scoring errors on 'early' sets of Wechsler scales were compared to those made on 'later' sets. However, correcting these subtest scoring errors did not cause significant changes in subtest scaled scores. Implications for clinical instruction and future research are discussed.

  4. Characterization of Portuguese Centenarian Eating Habits, Nutritional Biomarkers, and Cardiovascular Risk: A Case Control Study

    Directory of Open Access Journals (Sweden)

    A. Pereira da Silva

    2018-01-01

    Full Text Available Background and Aims. Eating habits may contribute to longevity. We characterized the eating habits and cardiovascular risk (CVR biomarkers in Portuguese centenarians (CENT compared to controls. Methods and Results. Centenarians (n=253, 100.26 ± 1.98 years, were compared with 268 controls (67.51 ± 3.25, low (LCR and high (HCR CVR (QRISK®2-2016. Anthropometric and body composition were evaluated by bioimpedance. Abdominal obesity, BMI, and fat mass (FM cut-offs were according to the WHO. Sarcopenia was defined by muscle mass index cut-off ≤ 16.7 kg/m2. Daily red meat intake, adjusted for age and gender, was sarcopenia protective (OR = 0.25, 95% CI = 0.096–0.670, P=0.006; however, it contributes for FM excess (OR = 4.946, 95% CI = 1.471–16.626, P=0.01, overweight, and obesity (OR = 4.804, 95% CI = 1.666–13.851, P=0.004. This centenarian eating habit (2% contrasts to HCR (64.3%. The history of red meat (P<0.0001 and canned/industrialized food intakes (P<0.0001 was associated with HCR. Basal metabolism was lower in centenarians versus LCR/HCR (CENT = 1176.78 ± 201.98; LCR = 1356.54 ± 170.65; HCR = 1561.33 ± 267.85; P<0.0001, BMI (CENT = 21.06 ± 3.68; LCR = 28.49 ± 4.69; HCR = 29.56 ± 5.26; P<0.0001, waist circumference (CENT = 85.29 ± 10.83; LCR = 96.02 ± 11.71; HCR = 104.50 ± 11.84; P<0.0001, and waist-hip ratio (CENT = 0.88 ± 0.07; LCR = 0.92 ± 0.08; HCR = 1.01 ± 0.08; P<0.0001. CENT had lower total cholesterol, LDL cholesterol, non-HDL cholesterol, and cholesterol/HDL ratio than controls. Conclusions. Frequent consumption of red meat, cholesterol, and heme iron rich may contribute to obesity and increased CVR. The low frequency of this consumption, observed in centenarians, although associated with sarcopenia, may be one of the keys to longevity.

  5. Study of the comprehension of the scientific method by members of a university health research laboratory.

    Science.gov (United States)

    Burlamaque-Neto, A C; Santos, G R; Lisbôa, L M; Goldim, J R; Machado, C L B; Matte, U; Giugliani, R

    2012-02-01

    In Brazil, scientific research is carried out mainly at universities, where professors coordinate research projects with the active participation of undergraduate and graduate students. However, there is no formal program for the teaching/learning of the scientific method. The objective of the present study was to evaluate the comprehension of the scientific method by students of health sciences who participate in scientific projects in an academic research laboratory. An observational descriptive cross-sectional study was conducted using Edgar Morin complexity as theoretical reference. In a semi-structured interview, students were asked to solve an abstract logical puzzle - TanGram. The collected data were analyzed using the hermeneutic-dialectic analysis method proposed by Minayo and discussed in terms of the theoretical reference of complexity. The students' concept of the scientific method is limited to participation in projects, stressing the execution of practical procedures as opposed to scientific thinking. The solving of the TanGram puzzle revealed that the students had difficulties in understanding questions and activities focused on subjects and their processes. Objective answers, even when dealing with personal issues, were also reflected on the students' opinions about the characteristics of a successful researcher. Students' difficulties concerning these issues may affect their scientific performance and result in poorly designed experiments. This is a preliminary study that should be extended to other centers of scientific research.

  6. A comprehensive study on Li-ion battery nail penetrations and the possible solutions

    International Nuclear Information System (INIS)

    Zhao, Rui; Liu, Jie; Gu, Junjie

    2017-01-01

    Li-ion batteries are the state-of-the-art power sources for portable electronics, electric vehicles, and aerospace applications. The safety issues regarding Li-ion batteries arouse particular attentions after several accidents reported in recent years. Among various abuse conditions, nail penetration is one of the most dangerous for Li-ion batteries due to the accumulated heat generation, which could give rise to the thermal runaway and could damage entire energy storage system. In this paper, an electrochemical-thermal coupling model is developed to study the nail penetration process of Li-ion batteries. By introducing joule heating at the nail location, the model shows good agreement with the testing results. With this verified model, a comprehensive parametric study is carried out to investigate the effects of battery capacity, internal resistance, and nail diameter on the electrochemical and thermal behaviors of Li-ion batteries during the penetration processes. Furthermore, three possible solutions to prevent the thermal runaway, which includes decreasing the state of charge, improving heat dissipation, and increasing contact resistance, are compared and discussed in detail based on a series of simulations. - Highlights: • A coupling model is developed to simulate Li-ion battery nail penetrations. • A contact resistance – contact area curve is plotted based on experiments. • Simulation results show good agreements with nail tests. • The behaviors of Li-ion batteries in different penetration scenarios are studied. • Possible strategies to prevent thermal runaway are investigated and discussed.

  7. A Pilot Study of Biomedical Text Comprehension using an Attention-Based Deep Neural Reader: Design and Experimental Analysis.

    Science.gov (United States)

    Kim, Seongsoon; Park, Donghyeon; Choi, Yonghwa; Lee, Kyubum; Kim, Byounggun; Jeon, Minji; Kim, Jihye; Tan, Aik Choon; Kang, Jaewoo

    2018-01-05

    With the development of artificial intelligence (AI) technology centered on deep-learning, the computer has evolved to a point where it can read a given text and answer a question based on the context of the text. Such a specific task is known as the task of machine comprehension. Existing machine comprehension tasks mostly use datasets of general texts, such as news articles or elementary school-level storybooks. However, no attempt has been made to determine whether an up-to-date deep learning-based machine comprehension model can also process scientific literature containing expert-level knowledge, especially in the biomedical domain. This study aims to investigate whether a machine comprehension model can process biomedical articles as well as general texts. Since there is no dataset for the biomedical literature comprehension task, our work includes generating a large-scale question answering dataset using PubMed and manually evaluating the generated dataset. We present an attention-based deep neural model tailored to the biomedical domain. To further enhance the performance of our model, we used a pretrained word vector and biomedical entity type embedding. We also developed an ensemble method of combining the results of several independent models to reduce the variance of the answers from the models. The experimental results showed that our proposed deep neural network model outperformed the baseline model by more than 7% on the new dataset. We also evaluated human performance on the new dataset. The human evaluation result showed that our deep neural model outperformed humans in comprehension by 22% on average. In this work, we introduced a new task of machine comprehension in the biomedical domain using a deep neural model. Since there was no large-scale dataset for training deep neural models in the biomedical domain, we created the new cloze-style datasets Biomedical Knowledge Comprehension Title (BMKC_T) and Biomedical Knowledge Comprehension Last

  8. Drinking water studies: a review on heavy metal, application of biomarker and health risk assessment (a special focus in Malaysia).

    Science.gov (United States)

    Ab Razak, Nurul Hafiza; Praveena, Sarva Mangala; Aris, Ahmad Zaharin; Hashim, Zailina

    2015-12-01

    Malaysia has abundant sources of drinking water from river and groundwater. However, rapid developments have deteriorated quality of drinking water sources in Malaysia. Heavy metal studies in terms of drinking water, applications of health risk assessment and bio-monitoring in Malaysia were reviewed from 2003 to 2013. Studies on heavy metal in drinking water showed the levels are under the permissible limits as suggested by World Health Organization and Malaysian Ministry of Health. Future studies on the applications of health risk assessment are crucial in order to understand the risk of heavy metal exposure through drinking water to Malaysian population. Among the biomarkers that have been reviewed, toenail is the most useful tool to evaluate body burden of heavy metal. Toenails are easy to collect, store, transport and analysed. This review will give a clear guidance for future studies of Malaysian drinking water. In this way, it will help risk managers to minimize the exposure at optimum level as well as the government to formulate policies in safe guarding the population. Copyright © 2015 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  9. Suitability of Yin Yang 1 transcript and protein levels for biomarker studies in B cell non-Hodgkin lymphoma.

    Science.gov (United States)

    Arribas Arranz, Jéssica; Winter, Dalia Nilufar; Drexler, Hans Günter; Eberth, Sonja

    2018-01-01

    Yin Yang 1 (YY1) is a transcription factor that plays an important role during all stages of B cell differentiation. Several studies reported upregulation of YY1 in B cell derived lymphoma, indicating that it might act as an oncogene. Furthermore, aberrant YY1 expression has been associated with survival in some entities of B cell non-Hodgkin lymphoma (B-NHL), suggesting that YY1 could be a valuable biomarker in B-NHL. However, studies are controversial and methodologically disparate, partially because some studies are based on transcript levels while others rely on YY1 protein data. Therefore, we aimed to investigate the dependence of YY1 protein levels on YY1 transcription. A panel of human cell lines representing different B-NHL subtypes was used to test for the correlation of YY1 mRNA and protein levels which were determined by quantitative PCR and immunoblotting. To analyze YY1 mRNA and YY1 protein stability cells were treated with actinomycin-D and cycloheximide, respectively. siRNAs were transfected to knockdown YY1 . Kaplan-Meier survival analyses were performed with data from published patient cohorts. Pearson's correlation analyses were assessed and statistical power was examined by Student's t-test. In the analyzed panel of B-NHL cell lines YY1 transcript levels do not correlate with their cellular protein amounts. YY1 protein levels were unaffected by transient block of transcription or by targeting YY1 mRNA using siRNA. Additionally, global inhibition of translation up to 48 h did not alter protein levels of YY1, indicating that YY1 is a highly stable protein in B-NHL. Furthermore, in a retrospective analysis of two different B-NHL cohorts, YY1 transcript levels had no impact on patients' survival probabilities. Our results point out the necessity to focus on YY1 protein expression to understand the potential role of YY1 as an oncogene and to unravel its suitability as clinical biomarker in B-NHL.

  10. Testing audiovisual comprehension tasks with questions embedded in videos as subtitles: a pilot multimethod study

    OpenAIRE

    Casañ Núñez, Juan Carlos

    2017-01-01

    [EN] Listening, watching, reading and writing simultaneously in a foreign language is very complex. This paper is part of wider research which explores the use of audiovisual comprehension questions imprinted in the video image in the form of subtitles and synchronized with the relevant fragments for the purpose of language learning and testing. Compared to viewings where the comprehension activity is available only on paper, this innovative methodology may provide some benefits. Among them, ...

  11. Development and validation of a score for evaluating comprehensive stroke care capabilities: J-ASPECT Study

    OpenAIRE

    Kada, Akiko; Nishimura, Kunihiro; Nakagawara, Jyoji; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Toyoda, Kazunori; Matsuda, Shinya; Suzuki, Akifumi; Kataoka, Hiroharu; Nakamura, Fumiaki; Kamitani, Satoru

    2017-01-01

    Background Although the Brain Attack Coalition recommended establishing centers of comprehensive care for stroke and cerebrovascular disease patients, a scoring system for such centers was lacking. We created and validated a comprehensive stroke center (CSC) score, adapted to Japanese circumstances. Methods Of the selected 1369 certified training institutions in Japan, 749 completed an acute stroke care capabilities survey. Hospital performance was determined using a 25-item score, evaluating...

  12. Comprehensive Longitudinal Study Challenges the Existence of Neonatal Imitation in Humans.

    Science.gov (United States)

    Oostenbroek, Janine; Suddendorf, Thomas; Nielsen, Mark; Redshaw, Jonathan; Kennedy-Costantini, Siobhan; Davis, Jacqueline; Clark, Sally; Slaughter, Virginia

    2016-05-23

    Human children copy others' actions with high fidelity, supporting early cultural learning and assisting in the development and maintenance of behavioral traditions [1]. Imitation has long been assumed to occur from birth [2-4], with influential theories (e.g., [5-7]) placing an innate imitation module at the foundation of social cognition (potentially underpinned by a mirror neuron system [8, 9]). Yet, the very phenomenon of neonatal imitation has remained controversial. Empirical support is mixed and interpretations are varied [10-16], potentially because previous investigations have relied heavily on cross-sectional designs with relatively small samples and with limited controls [17, 18]. Here, we report surprising results from the most comprehensive longitudinal study of neonatal imitation to date. We presented infants (n = 106) with nine social and two non-social models and scored their responses at 1, 3, 6, and 9 weeks of age. Longitudinal analyses indicated that the infants did not imitate any of the models, as they were just as likely to produce the gestures in response to control models as they were to matching models. Previous positive findings were replicated in limited cross-sections of the data, but the overall analyses confirmed these findings to be mere artifacts of restricted comparison conditions. Our results undermine the idea of an innate imitation module and suggest that earlier studies reporting neonatal imitation were methodologically limited. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Comprehensive studies on the interactions between chitosan nanoparticles and some live cells

    International Nuclear Information System (INIS)

    Zheng Aiping; Liu Huixue; Yuan Lan; Meng Meng; Wang Jiancheng; Zhang Xuan; Zhang Qiang

    2011-01-01

    As more and more oral formulations of nanoparticles are used in clinical contexts, a comprehensive study on the mechanisms of interaction between polymer nanoparticles and live cells seems merited. Such a study was conducted and the results were compared to the polymer itself in order to demonstrate different kinds of effects that are brought into the cell by polymer and its nanoparticles, especially the effects on the biomembrane. Several techniques, including surface plasmon resonance (SPR), Fourier transformed infrared spectroscopy (FTIR), Raman spectroscopy, fluorescence polarization spectroscopy (FP), flow cytometry (FCM) with quantitative analysis, and confocal images with antibody staining were employed toward this end. The cytotoxicity in vitro was also evaluated. Chitosan (CS), a polycationic polymer, was used to prepare the nanoparticles. We demonstrate that chitosan nanoparticles (CS-NP) induce strong alterations in the distribution of membrane proteins, fluidity of membrane lipids, and general membrane structure. Furthermore, the uptake of CS-NP into Caco-2 cells was found to have a similar mechanism to that of CS molecules, but the differences in degree were noted. These results indicate that positive charge and nanoscale size were the factors that most significantly affected the interactions between the nanoparticles of polycationic polymers and live cells. However, no difference in cytotoxicity toward the Caco-2 cells was found between CS and CS-NP. This supports the idea that CS-NP is an effective and safe carrier for oral drug delivery.

  14. Surgeons' physical discomfort and symptoms during robotic surgery: a comprehensive ergonomic survey study.

    Science.gov (United States)

    Lee, G I; Lee, M R; Green, I; Allaf, M; Marohn, M R

    2017-04-01

    It is commonly believed that robotic surgery systems provide surgeons with an ergonomically sound work environment; however, the actual experience of surgeons practicing robotic surgery (RS) has not been thoroughly researched. In this ergonomics survey study, we investigated surgeons' physical symptom reports and their association with factors including demographics, specialties, and robotic systems. Four hundred and thirty-two surgeons regularly practicing RS completed this comprehensive survey comprising 20 questions in four categories: demographics, systems, ergonomics, and physical symptoms. Chi-square and multinomial logistic regression analyses were used for statistical analysis. Two hundred and thirty-six surgeons (56.1 %) reported physical symptoms or discomfort. Among those symptoms, neck stiffness, finger, and eye fatigues were the most common. With the newest robot, eye symptom rate was considerably reduced, while neck and finger symptoms did not improve significantly. A high rate of lower back stiffness was correlated with higher annual robotic case volume, and eye symptoms were more common with longer years practicing robotic surgery (p ergonomic settings reported lower symptom report rates. Symptoms were not correlated with age and gender. Although RS provides relatively better ergonomics, this study demonstrates that 56.1 % of regularly practicing robotic surgeons still experience related physical symptoms or discomfort. In addition to system improvement, surgeon education in optimizing the ergonomic settings may be necessary to maximize the ergonomic benefits in RS.

  15. Comprehensive adsorption studies of doxycycline and ciprofloxacin antibiotics by biochars prepared at different temperatures

    Science.gov (United States)

    Zeng, Zhi-wei; Tan, Xiao-fei; Liu, Yun-guo; Tian, Si-rong; Zeng, Guang-ming; Jiang, Lu-hua; Liu, Shao-bo; Li, Jiang; Liu, Ni; Yin, Zhi-hong

    2018-03-01

    This paper comparatively investigated the removal efficiency and mechanisms of rice straw biochars prepared under three pyrolytic temperatures for two kinds of tetracycline and quinolone antibiotics (doxycycline and ciprofloxacin). The influencing factors of antibiotic adsorption (including biochar dosage, pH, background electrolytes, humic acid, initial antibiotics concentration, contact time, and temperature) were comprehensively studied. The results suggest that biochars produced at high-temperature (i.e., 700°C (BC700)), have higher adsorption capacity for the two antibiotics than low-temperature (i.e., 300-500°C) biochars (BC300 and BC500). Higher surface area gives rise to greater volume of micropores and mesopores, and higher graphitic surfaces of the BC700 contributed to its higher functionality. The maximum adsorption capacity was found to be in the following order: DOX > CIP. The π-π EDA interaction and hydrogen bonding might be the predominant adsorption mechanisms. Findings in this study highlight the important roles of high-temperature biochars in controlling the contamination of tetracycline and quinolone antibiotics in the environment.

  16. Comprehensive Adsorption Studies of Doxycycline and Ciprofloxacin Antibiotics by Biochars Prepared at Different Temperatures

    Science.gov (United States)

    Zeng, Zhi-wei; Tan, Xiao-fei; Liu, Yun-guo; Tian, Si-rong; Zeng, Guang-ming; Jiang, Lu-hua; Liu, Shao-bo; Li, Jiang; Liu, Ni; Yin, Zhi-hong

    2018-01-01

    This paper comparatively investigated the removal efficiency and mechanisms of rice straw biochars prepared under three pyrolytic temperatures for two kinds of tetracycline and quinolone antibiotics (doxycycline and ciprofloxacin). The influencing factors of antibiotic adsorption (including biochar dosage, pH, background electrolytes, humic acid, initial antibiotics concentration, contact time, and temperature) were comprehensively studied. The results suggest that biochars produced at high-temperature [i.e., 700°C (BC700)], have higher adsorption capacity for the two antibiotics than low-temperature (i.e., 300–500°C) biochars (BC300 and BC500). Higher surface area gives rise to greater volume of micropores and mesopores, and higher graphitic surfaces of the BC700 contributed to its higher functionality. The maximum adsorption capacity was found to be in the following order: DOX > CIP. The π-π EDA interaction and hydrogen bonding might be the predominant adsorption mechanisms. Findings in this study highlight the important roles of high-temperature biochars in controlling the contamination of tetracycline and quinolone antibiotics in the environment. PMID:29637067

  17. Comprehensive maternal characteristics associated with birth weight: Bayesian modeling in a prospective cohort study from Iran

    Directory of Open Access Journals (Sweden)

    Marjan Mansourian

    2017-01-01

    Full Text Available Background: In this study, we aimed to determine comprehensive maternal characteristics associated with birth weight using Bayesian modeling. Materials and Methods: A total of 526 participants were included in this prospective study. Nutritional status, supplement consumption during the pregnancy, demographic and socioeconomic characteristics, anthropometric measures, physical activity, and pregnancy outcomes were considered as effective variables on the birth weight. Bayesian approach of complex statistical models using Markov chain Monte Carlo approach was used for modeling the data considering the real distribution of the response variable. Results: There was strong positive correlation between infant birth weight and the maternal intake of Vitamin C, folic acid, Vitamin B3, Vitamin A, selenium, calcium, iron, phosphorus, potassium, magnesium as micronutrients, and fiber and protein as macronutrients based on the 95% high posterior density regions for parameters in the Bayesian model. None of the maternal characteristics had statistical association with birth weight. Conclusion: Higher maternal macro- and micro-nutrient intake during pregnancy was associated with a lower risk of delivering low birth weight infants. These findings support recommendations to expand intake of nutrients during pregnancy to high level.

  18. Dietary long-chain fatty acids and carbohydrate biomarker evaluation in a controlled feeding study in participants from the Women's Health Initiative cohort.

    Science.gov (United States)

    Song, Xiaoling; Huang, Ying; Neuhouser, Marian L; Tinker, Lesley F; Vitolins, Mara Z; Prentice, Ross L; Lampe, Johanna W

    2017-06-01

    Background: Biomarkers of macronutrient intake are lacking. Controlled human feeding studies that preserve the normal variation in nutrient and food consumption are necessary for the development and validation of robust nutritional biomarkers. Objective: We aimed to assess the utility of serum phospholipid fatty acids (PLFAs) as biomarkers of dietary intakes of fatty acids, total fat, and carbohydrate. Design: We used an individualized controlled feeding study in which 153 postmenopausal women from the Women's Health Initiative (WHI) were provided with a 2-wk controlled diet that mimicked each individual's habitual food intake. A total of 41 PLFAs were measured with the use of gas chromatography in end-of-feeding-period fasting serum samples and expressed in both relative and absolute concentrations. R 2 values (percentages of variation explained) from linear regressions of (ln-transformed) consumed fatty acids (individual, groups, and broad categories) on (ln-transformed) corresponding measures of serum PLFAs alone and together with selected participant-related variables (age, race/ethnicity, body mass index, season of study participation, education level, and estimated energy intake from doubly labeled water) were used for evaluation against established urinary recovery biomarkers of energy and protein intake as benchmarks. Models to predict intakes of other nutrients were also explored. Results: Intakes of eicosapentaenoic acid and docosahexaenoic acid achieved the benchmark of R 2 > 36% with or without covariates. When all 41 serum PLFAs and participant-related covariates were initially included in the model for selection, cross-validated R 2 achieved >36% for consumed total carbohydrate (grams per day), total saturated fatty acids (SFAs), percentage of energy from SFAs, and total trans fatty acids with serum PLFAs in both relative and absolute concentrations. Conclusions: Serum PLFA biomarkers perform similarly to established energy and protein urinary

  19. A proposed panel of biomarkers of healthy ageing.

    Science.gov (United States)

    Lara, Jose; Cooper, Rachel; Nissan, Jack; Ginty, Annie T; Khaw, Kay-Tee; Deary, Ian J; Lord, Janet M; Kuh, Diana; Mathers, John C

    2015-09-15

    There is no criterion reference for assessing healthy ageing and this creates difficulties when conducting and comparing research on ageing across studies. A cardinal feature of ageing is loss of function which translates into wide-ranging consequences for the individual and for family, carers and society. We undertook comprehensive reviews of the literature searching for biomarkers of ageing on five ageing-related domains including physical capability and cognitive, physiological and musculoskeletal, endocrine and immune functions. Where available, we used existing systematic reviews, meta-analyses and other authoritative reports such as the recently launched NIH Toolbox for assessment of neurological and behavioural function, which includes test batteries for cognitive and motor function (the latter described here as physical capability). We invited international experts to comment on our draft recommendations. In addition, we hosted an experts workshop in Newcastle, UK, on 22-23 October 2012, aiming to help capture the state-of-the-art in this complex area and to provide an opportunity for the wider ageing research community to critique the proposed panel of biomarkers. Here we have identified important biomarkers of healthy ageing classified as subdomains of the main areas proposed. Cardiovascular and lung function, glucose metabolism and musculoskeletal function are key subdomains of physiological function. Strength, locomotion, balance and dexterity are key physical capability subdomains. Memory, processing speed and executive function emerged as key subdomains of cognitive function. Markers of the HPA-axis, sex hormones and growth hormones were important biomarkers of endocrine function. Finally, inflammatory factors were identified as important biomarkers of immune function. We present recommendations for a panel of biomarkers that address these major areas of function which decline during ageing. This biomarker panel may have utility in epidemiological

  20. The "BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons" (BIOSPHERE) study: Rationale, design and methods.

    Science.gov (United States)

    Calvani, Riccardo; Picca, Anna; Marini, Federico; Biancolillo, Alessandra; Cesari, Matteo; Pesce, Vito; Lezza, Angela Maria Serena; Bossola, Maurizio; Leeuwenburgh, Christiaan; Bernabei, Roberto; Landi, Francesco; Marzetti, Emanuele

    2018-05-10

    Sarcopenia, the progressive and generalised loss of muscle mass and strength/function, is a major health issue in older adults given its high prevalence and burdensome clinical implications. Over the years, this condition has been endorsed as a marker for discriminating biological from chronological age. However, the absence of a unified operational definition has hampered its full appreciation by healthcare providers, researchers and policy-makers. In addition to this unsolved debate, the complexity of musculoskeletal ageing represents a major challenge to the identification of clinically meaningful biomarkers. Here, we illustrate the advantages of biomarker discovery procedures in muscle ageing based on multivariate methodologies as an alternative approach to traditional single-marker strategies. The rationale, design and methods of the "BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons" (BIOSPHERE) study are described as an application of a multi-marker strategy for the development of biomarkers for the newly operationalised Physical Frailty & Sarcopenia condition. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  1. miRNA as potential biomarkers of breast cancer in the Lebanese population and in young women: a pilot study.

    Directory of Open Access Journals (Sweden)

    Farah J Nassar

    Full Text Available Relative to western populations, the percentage of women diagnosed with breast cancer at a young age in Lebanon is high. While the younger age of the Lebanese population compared to the West certainly contributes to this difference, potential genetic, reproductive and/or biological factors likely play an important role. The objective of this study is to investigate the contribution of miRNAs in this setting through the analysis of the expression of five reported dysregulated miRNAs, miR-148b, miR-10b, miR-21, miR-221, and miR-155 in 20 normal and 57 cancerous breast tissues from Lebanese breast cancer patients. After finding their relative expression by quantitative reverse transcription real time PCR, the results were analyzed with respect to the patients' clinical and histopathology presentations. Compared to normal breast tissues, significant upregulation of miR-155, miR-21 and miR-148b, notable downregulation of miR-10b and non-significant expression of miR-221 were observed in tumor tissues. Moreover, miR-10b was significantly underexpressed in estrogen/progesterone receptor (ER/PR negative tumors relative to ER/PR positive tumor tissues. miR-155 was also significantly overexpressed in postmenopausal patients and in those of age at diagnosis greater than 40 years old as well as in PR negative or in human epidermal growth factor 2 (Her2 positive tissues. This study is the first one to report miRNA expression patterns in Lebanese breast cancer patients. We found that differential miRNA expression in breast cancer could be variable between Lebanese and Western populations. miR-10b was positively correlated with the ER and PR status and miR-155 could be a noteworthy biomarker for the menopausal state, age at diagnosis, PR and Her2 status. Hence, miRNA can be used as biomarkers for early breast cancer detection.

  2. CBD: a biomarker database for colorectal cancer.

    Science.gov (United States)

    Zhang, Xueli; Sun, Xiao-Feng; Cao, Yang; Ye, Benchen; Peng, Qiliang; Liu, Xingyun; Shen, Bairong; Zhang, Hong

    2018-01-01

    Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD.Database URL: http://sysbio.suda.edu.cn/CBD/.

  3. Applying Language Learning Strategies in the Foreign Language Listening Comprehension: A Study of Islamic Senior High School Students

    Directory of Open Access Journals (Sweden)

    DIAN PERTIWI

    2018-05-01

    Full Text Available The main purpose of the present study was to empirically investigate the possible correlation and the influence between students’ language learning strategies and listening comprehension. The population of this study was 138 eleventh grade students of Islamic Senior High School number 2 Palembang. The sample was all of eleventh grade students in social class. The total number of the student was 138. Since 16 students were absent, so the sample consisted of 122 students. To collect the data in order to measure the students’ language learning strategies and listening comprehension, SILL (strategy inventory in learning language and listening comprehension test from TOEFL Junior test were used in this study. The Pearson correlation was used in analyzing the data using SPSS 16. The result from questionnaire showed that most of the students used metacognitive strategies were in medium level and sometimes used language learning strategies. The result from listening comprehension test showed that most of the students were in very poor level. Furthermore, there was no significant correlation between the two variables that can be seen from the correlation coefficient or r-obtained (-.011 was lower than r-table (0.1779 then the level of probability or sig. value (.902 was higher than .05. From the result, it can be concluded that there was no significant correlation between language learning strategies and listening comprehension of eleventh grade students of Islamic Senior High School number 2 Palembang.

  4. Enlarged pulmonary artery is predicted by vascular injury biomarkers and is associated with WTC-Lung Injury in exposed fire fighters: a case–control study

    Science.gov (United States)

    Schenck, Edward J; Echevarria, Ghislaine C; Girvin, Francis G; Kwon, Sophia; Comfort, Ashley L; Rom, William N; Prezant, David J; Weiden, Michael D; Nolan, Anna

    2014-01-01

    Objectives We hypothesise that there is an association between an elevated pulmonary artery/aorta (PA/A) and World Trade Center-Lung Injury (WTC-LI). We assessed if serum vascular disease biomarkers were predictive of an elevated PA/A. Design Retrospective case-cohort analysis of thoracic CT scans of WTC-exposed firefighters who were symptomatic between 9/12/2001 and 3/10/2008. Quantification of vascular-associated biomarkers from serum collected within 200 days of exposure. Setting Urban tertiary care centre and occupational healthcare centre. Participants Male never-smoking firefighters with accurate pre-9/11 forced expiratory volume in 1 s (FEV1) ≥75%, serum sampled ≤200 days of exposure was the baseline cohort (n=801). A subcohort (n=97) with available CT scans and serum biomarkers was identified. WTC-LI was defined as FEV1≤77% at the subspecialty pulmonary evaluation (n=34) and compared with controls (n=63) to determine the associated PA/A ratio. The subcohort was restratified based on PA/A≥0.92 (n=38) and PA/A<0.92(n=59) to determine serum vascular biomarkers that were predictive of this vasculopathy. Outcome measures The primary outcome of this study was to identify a PA/A ratio in a cohort of individuals exposed to WTC dust that was associated with WTC-LI. The secondary outcome was to identify serum biomarkers predictive of the PA/A ratio using logistic regression. Results PA/A≥0.92 was associated with WTC-LI, OR of 4.02 (95% CI 1.21 to 13.41; p=0.023) when adjusted for exposure, body mass index and age at CT. Elevated macrophage derived chemokine and soluble endothelial selectin were predictive of PA/A≥0.92, (OR, 95% CI 2.08, 1.05 to 4.11, p=0.036; 1.33, 1.06 to 1.68, p=0.016, respectively), while the increased total plasminogen activator inhibitor 1 was predictive of not having PA/A≥0.92 (OR 0.88, 0.79 to 0.98; p=0.024). Conclusions Elevated PA/A was associated with WTC-LI. Development of an elevated PA/A was predicted by biomarkers of

  5. Top-down proteomics with mass spectrometry imaging: a pilot study towards discovery of biomarkers for neurodevelopmental disorders.

    Directory of Open Access Journals (Sweden)

    Hui Ye

    Full Text Available In the developing mammalian brain, inhibition of NMDA receptor can induce widespread neuroapoptosis, inhibit neurogenesis and cause impairment of learning and memory. Although some mechanistic insights into adverse neurological actions of these NMDA receptor antagonists exist, our understanding of the full spectrum of developmental events affected by early exposure to these chemical agents in the brain is still limited. Here we attempt to gain insights into the impact of pharmacologically induced excitatory/inhibitory imbalance in infancy on the brain proteome using mass spectrometric imaging (MSI. Our goal was to study changes in protein expression in postnatal day 10 (P10 rat brains following neonatal exposure to the NMDA receptor antagonist dizocilpine (MK801. Analysis of rat brains exposed to vehicle or MK801 and comparison of their MALDI MS images revealed differential relative abundances of several proteins. We then identified these markers such as ubiquitin, purkinje cell protein 4 (PEP-19, cytochrome c oxidase subunits and calmodulin, by a combination of reversed-phase (RP HPLC fractionation and top-down tandem MS platform. More in-depth large scale study along with validation experiments will be carried out in the future. Overall, our findings indicate that a brief neonatal exposure to a compound that alters excitatory/inhibitory balance in the brain has a long term effect on protein expression patterns during subsequent development, highlighting the utility of MALDI-MSI as a discovery tool for potential biomarkers.

  6. Study of secondhand smoke levels pre and post implementation of the comprehensive smoking ban in Mumbai

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    Deshpande Aditi

    2010-01-01

    Full Text Available Objectives: This research was undertaken with the aim of assessing the indoor air quality in popular hospitality venues, as also to evaluate the effectiveness of the nationwide comprehensive public smoking ban. The analysis was split into two halves - baseline study taken up prior to implementation of the said ban on 2 nd October 2008, and the follow-up study after it came into effect. Materials and Methods: Twenty-five venues including five restaurants, fourteen resto-bars, two hookah (smoking water-pipe cafes and four pubs were selected using a mix of random, convenience and purposeful sampling. Particulate matter (PM 2.5 measurements at these venues were made using TSI SidePak AM510 Personal Aerosol Monitor. Results: The average PM 2.5 level in venues where smoking was permitted prior to implementation of ban was found to be 669.95 ΅g/m 3 in the baseline study. Post ban, the average PM 2.5 level in same test venues reduced to 240.8 ΅g/m 3 . The hookah cafes were an exception as the average PM 2.5 levels exceeded the permissible limits before as well as post ban. Conclusion: The baseline study showed that the hospitality venues had hazardous levels of PM 2.5 particles arising from second-hand smoke prior to smoking ban. These decreased by a maximum of 64% after the law took effect. A substantial improvement in air quality at these venues post implementation of the smoking ban indicated the effectiveness of the law.

  7. Primary motor cortex functionally contributes to language comprehension: An online rTMS study.

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    Vukovic, Nikola; Feurra, Matteo; Shpektor, Anna; Myachykov, Andriy; Shtyrov, Yury

    2017-02-01

    Among various questions pertinent to grounding human cognitive functions in a neurobiological substrate, the association between language and motor brain structures is a particularly debated one in neuroscience and psychology. While many studies support a broadly distributed model of language and semantics grounded, among other things, in the general modality-specific systems, theories disagree as to whether motor and sensory cortex activity observed during language processing is functional or epiphenomenal. Here, we assessed the role of motor areas in linguistic processing by investigating the responses of 28 healthy volunteers to different word types in semantic and lexical decision tasks, following repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex. We found that early rTMS (delivered within 200ms of word onset) produces a left-lateralised and meaning-specific change in reaction speed, slowing down behavioural responses to action-related words, and facilitating abstract words - an effect present only during semantic, but not lexical, decision. We interpret these data in light of action-perception theory of language, bolstering the claim that motor cortical areas play a functional role in language comprehension. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.

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    Le Quesne Stabej, Polona; Saihan, Zubin; Rangesh, Nell; Steele-Stallard, Heather B; Ambrose, John; Coffey, Alison; Emmerson, Jenny; Haralambous, Elene; Hughes, Yasmin; Steel, Karen P; Luxon, Linda M; Webster, Andrew R; Bitner-Glindzicz, Maria

    2012-01-01

    Usher syndrome (USH) is an autosomal recessive disorder comprising retinitis pigmentosa, hearing loss and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous with three distinctive clinical types (I-III) and nine Usher genes identified. This study is a comprehensive clinical and genetic analysis of 172 Usher patients and evaluates the contribution of digenic inheritance. The genes MYO7A, USH1C, CDH23, PCDH15, USH1G, USH2A, GPR98, WHRN, CLRN1 and the candidate gene SLC4A7 were sequenced in 172 UK Usher patients, regardless of clinical type. No subject had definite mutations (nonsense, frameshift or consensus splice site mutations) in two different USH genes. Novel missense variants were classified UV1-4 (unclassified variant): UV4 is 'probably pathogenic', based on control frequency A being the most common USH1 mutation in the cohort). USH2A was responsible for 79.3% of USH2 families and GPR98 for only 6.6%. No mutations were found in USH1G, WHRN or SLC4A7. One or two pathogenic/likely pathogenic variants were identified in 86% of cases. No convincing cases of digenic inheritance were found. It is concluded that digenic inheritance does not make a significant contribution to Usher syndrome; the observation of multiple variants in different genes is likely to reflect polymorphic variation, rather than digenic effects.

  9. International and Domestic Challenges to Comprehensive National Cybersecurity: A Case Study of the Czech Republic

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    Nadiya Kostyuk

    2014-04-01

    Full Text Available While many countries and companies have fallen victim to cyber attacks over the past few years, including American companies such as Apple, Microsoft, and Facebook, Czech websites remained relatively safe until March 2013, when they were interrupted by a series of cyber attacks. Even though the origin of the attacks remains debatable, this case study demonstrates the importance of cooperation between nations in the nascent phase of the internet development and their more powerful allies. Domestic challenges that nations face in addressing cybersecurity in an effective and comprehensive manner include ambiguous legislation, recalcitrant officials, and a lack of both fiscal and human capital. To address these challenges, nations should cooperate with their more capable allies, such as the EU and NATO, create better cyber protective measures, train and hire qualified specialists in the public sector, and intensify private-public partnership. Until an international agenda on cyberspace is set, these nations with limited resources should cooperate with developed nations lest they risk more severe attacks in the future.

  10. Comprehensive Study of Lanthanum Aluminate High-Dielectric-Constant Gate Oxides for Advanced CMOS Devices

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    Masamichi Suzuki

    2012-03-01

    Full Text Available A comprehensive study of the electrical and physical characteristics of Lanthanum Aluminate (LaAlO3 high-dielectric-constant gate oxides for advanced CMOS devices was performed. The most distinctive feature of LaAlO3 as compared with Hf-based high-k materials is the thermal stability at the interface with Si, which suppresses the formation of a low-permittivity Si oxide interfacial layer. Careful selection of the film deposition conditions has enabled successful deposition of an LaAlO3 gate dielectric film with an equivalent oxide thickness (EOT of 0.31 nm. Direct contact with Si has been revealed to cause significant tensile strain to the Si in the interface region. The high stability of the effective work function with respect to the annealing conditions has been demonstrated through comparison with Hf-based dielectrics. It has also been shown that the effective work function can be tuned over a wide range by controlling the La/(La + Al atomic ratio. In addition, gate-first n-MOSFETs with ultrathin EOT that use sulfur-implanted Schottky source/drain technology have been fabricated using a low-temperature process.

  11. A Comprehensive Study on the Internet of Underwater Things: Applications, Challenges, and Channel Models

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    Chien-Chi Kao

    2017-06-01

    Full Text Available The Internet of Underwater Things (IoUT is a novel class of Internet of Things (IoT, and is defined as the network of smart interconnected underwater objects. IoUT is expected to enable various practical applications, such as environmental monitoring, underwater exploration, and disaster prevention. With these applications, IoUT is regarded as one of the potential technologies toward developing smart cities. To support the concept of IoUT, Underwater Wireless Sensor Networks (UWSNs have emerged as a promising network system. UWSNs are different from the traditional Territorial Wireless Sensor Networks (TWSNs, and have several unique properties, such as long propagation delay, narrow bandwidth, and low reliability. These unique properties would be great challenges for IoUT. In this paper, we provide a comprehensive study of IoUT, and the main contributions of this paper are threefold: (1 we introduce and classify the practical underwater applications that can highlight the importance of IoUT; (2 we point out the differences between UWSNs and traditional TWSNs, and these differences are the main challenges for IoUT; and (3 we investigate and evaluate the channel models, which are the technical core for designing reliable communication protocols on IoUT.

  12. A Comprehensive Study on the Internet of Underwater Things: Applications, Challenges, and Channel Models.

    Science.gov (United States)

    Kao, Chien-Chi; Lin, Yi-Shan; Wu, Geng-De; Huang, Chun-Ju

    2017-06-22

    The Internet of Underwater Things (IoUT) is a novel class of Internet of Things (IoT), and is defined as the network of smart interconnected underwater objects. IoUT is expected to enable various practical applications, such as environmental monitoring, underwater exploration, and disaster prevention. With these applications, IoUT is regarded as one of the potential technologies toward developing smart cities. To support the concept of IoUT, Underwater Wireless Sensor Networks (UWSNs) have emerged as a promising network system. UWSNs are different from the traditional Territorial Wireless Sensor Networks (TWSNs), and have several unique properties, such as long propagation delay, narrow bandwidth, and low reliability. These unique properties would be great challenges for IoUT. In this paper, we provide a comprehensive study of IoUT, and the main contributions of this paper are threefold: (1) we introduce and classify the practical underwater applications that can highlight the importance of IoUT; (2) we point out the differences between UWSNs and traditional TWSNs, and these differences are the main challenges for IoUT; and (3) we investigate and evaluate the channel models, which are the technical core for designing reliable communication protocols on IoUT.

  13. A Comprehensive Study of the Polypropylene Fiber Reinforced Fly Ash Based Geopolymer.

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    Navid Ranjbar

    Full Text Available As a cementitious material, geopolymers show a high quasi-brittle behavior and a relatively low fracture energy. To overcome such a weakness, incorporation of fibers to a brittle matrix is a well-known technique to enhance the flexural properties. This study comprehensively evaluates the short and long term impacts of different volume percentages of polypropylene fiber (PPF reinforcement on fly ash based geopolymer composites. Different characteristics of the composite were compared at fresh state by flow measurement and hardened state by variation of shrinkage over time to assess the response of composites under flexural and compressive load conditions. The fiber-matrix interface, fiber surface and toughening