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Sample records for biomarker validation study

  1. 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...

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

    DEFF Research Database (Denmark)

    Gallo, Valentina; Khan, Aneire; Gonzales, Carlos;

    2008-01-01

    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...

  3. 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...

  4. Validating Biomarkers for PTSD

    Science.gov (United States)

    2015-04-01

    Months 3-21, Tasks: 1. Outreach and recruitment via flyers, presentations, website newspaper and television advertisements, informal letters...NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 TABLE OF CONTENTS Page No. 1. Introduction 4 2. Keywords 4 3... analysis Timeframe: Months 7-22, 1. Obtain Archived Sera data, remove PII, and distribute information to appropriate team members for omic studies 2

  5. 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...

  6. Proposal for levels of evidence schema for validation of a soluble biomarker reflecting damage endpoints in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, and recommendations for study design

    DEFF Research Database (Denmark)

    Maksymowych, Walter P; Fitzgerald, Oliver; Wells, George A

    2009-01-01

    arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We also aimed to generate consensus on minimum standards for the design of longitudinal studies aimed at validating biomarkers. METHODS: Before the meeting, the Soluble Biomarker Working Group prepared a preliminary framework...... and discussed various models for association and prediction related to the statistical strength domain. In addition, 3 Delphi exercises addressing longitudinal study design for RA, PsA, and AS were conducted within the working group and members of the Assessments in SpondyloArthritis International Society (ASAS...... Biomarker Group has successfully formulated a levels of evidence scheme and a study design template that will provide guidance to conduct validation studies in the setting of soluble biomarkers proposed to replace the measurement of damage endpoints in RA, PsA, and AS....

  7. 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

    liver in an estrogen dependent manner (Aarskog et al., 1983). GSC has been shown to be widely distributed in the tissues, and this protein or its...highly polymorphic serum protein, and studies have linked GSC variants to osteoporosis , Graves’ disease, Hashimoto’s thyroiditis, diabetes, COPD, AIDS...185 5. REFERENCES Aarskog D, Aksnes L, Markestad T, and Rodland O, “Effect of estrogen on vitamin D metabolism in tall girls,” The Journal of

  8. Proposal for levels of evidence schema for validation of a soluble biomarker reflecting damage endpoints in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, and recommendations for study design

    DEFF Research Database (Denmark)

    Maksymowych, W.P.; Fitzgerald, O.; Wells, G.A.

    2009-01-01

    arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We also aimed to generate consensus on minimum standards for the design of longitudinal studies aimed at validating biomarkers. METHODS: Before the meeting, the Soluble Biomarker Working Group prepared a preliminary framework...... and discussed various models for association and prediction related to the statistical strength domain. In addition, 3 Delphi exercises addressing longitudinal study design for RA, PsA, and AS were conducted within the working group and members of the Assessments in SpondyloArthritis International Society (ASAS...

  9. Laser scanning cytometry as a tool for biomarker validation

    Science.gov (United States)

    Mittag, Anja; Füldner, Christiane; Lehmann, Jörg; Tarnok, Attila

    2013-03-01

    Biomarkers are essential for diagnosis, prognosis, and therapy. As diverse is the range of diseases the broad is the range of biomarkers and the material used for analysis. Whereas body fluids can be relatively easily obtained and analyzed, the investigation of tissue is in most cases more complicated. The same applies for the screening and the evaluation of new biomarkers and the estimation of the binding of biomarkers found in animal models which need to be transferred into applications in humans. The latter in particular is difficult if it recognizes proteins or cells in tissue. A better way to find suitable cellular biomarkers for immunoscintigraphy or PET analyses may be therefore the in situ analysis of the cells in the respective tissue. In this study we present a method for biomarker validation using Laser Scanning Cytometry which allows the emulation of future in vivo analysis. The biomarker validation is exemplarily shown for rheumatoid arthritis (RA) on synovial membrane. Cryosections were scanned and analyzed by phantom contouring. Adequate statistical methods allowed the identification of suitable markers and combinations. The fluorescence analysis of the phantoms allowed the discrimination between synovial membrane of RA patients and non-RA control sections by using median fluorescence intensity and the "affected area". As intensity and area are relevant parameters of in vivo imaging (e.g. PET scan) too, the presented method allows emulation of a probable outcome of in vivo imaging, i.e. the binding of the target protein and hence, the validation of the potential of the respective biomarker.

  10. Validation of Biomarker-based risk prediction models

    OpenAIRE

    Taylor, Jeremy M.G.; Ankerst, Donna P.; Andridge, Rebecca R.

    2008-01-01

    The increasing availability and use of predictive models to facilitate informed decision making highlights the need for careful assessment of the validity of these models. In particular, models involving biomarkers require careful validation for two reasons: issues with overfitting when complex models involve a large number of biomarkers, and inter-laboratory variation in assays used to measure biomarkers. In this paper we distinguish between internal and external statistical validation. Inte...

  11. Addressing the Challenge of Defining Valid Proteomic Biomarkers and Classifiers

    LENUS (Irish Health Repository)

    Dakna, Mohammed

    2010-12-10

    Abstract Background The purpose of this manuscript is to provide, based on an extensive analysis of a proteomic data set, suggestions for proper statistical analysis for the discovery of sets of clinically relevant biomarkers. As tractable example we define the measurable proteomic differences between apparently healthy adult males and females. We choose urine as body-fluid of interest and CE-MS, a thoroughly validated platform technology, allowing for routine analysis of a large number of samples. The second urine of the morning was collected from apparently healthy male and female volunteers (aged 21-40) in the course of the routine medical check-up before recruitment at the Hannover Medical School. Results We found that the Wilcoxon-test is best suited for the definition of potential biomarkers. Adjustment for multiple testing is necessary. Sample size estimation can be performed based on a small number of observations via resampling from pilot data. Machine learning algorithms appear ideally suited to generate classifiers. Assessment of any results in an independent test-set is essential. Conclusions Valid proteomic biomarkers for diagnosis and prognosis only can be defined by applying proper statistical data mining procedures. In particular, a justification of the sample size should be part of the study design.

  12. Coefficient of Variation, Signal-to-Noise Ratio, and Effects of Normalization in Validation of Biomarkers from NMR-based Metabonomics Studies.

    Science.gov (United States)

    Wang, Bo; Goodpaster, Aaron M; Kennedy, Michael A

    2013-10-15

    A primary goal of metabonomics research is biomarker discovery for human diseases based on differences in metabolic profiles between healthy and diseased patient populations. One of the most significant challenges in biomarker discovery is validation, which implicitly depends on the coefficient of variation (CV) associated with the measurement technique. This paper investigates how the CV of metabolite resonances measured by nuclear magnetic resonance spectroscopy (NMR) depends on signal-to-noise ratio (SNR) and normalization method. CVs were calculated for NMR resonance peaks in a series of NMR spectra of five synthetic urine samples collected over an eight-month period. An inverse correlation was detected between SNR and CV for all normalization methods. Small peaks with SNR150, which typically had smaller CVs (5-10%). The inverse relationship between CV and SNR roughly obeyed a log10 dependence. Quotient normalization (QN) tended to produce smaller CVs for smaller peaks, but larger CVs for the strongest peaks in the data, compared to no normalization, normalization to total intensity (NTI) or normalization to an internal standard (NIS). Consequently, quotient normalization appears optimal for validating low concentration metabolites. NTI or NIS appear superior to QN for samples that have very small variation in total signal intensity. While the inverse relationship between CV and log10(SNR) did not strictly hold for all metabolites, weaker concentration metabolites will likely require more rigorous validation as potential biomarkers since they tend to have poorer reproducibility.

  13. Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma

    DEFF Research Database (Denmark)

    Daugaard, Iben; Dominguez, Diana; Kjeldsen, Tina E;

    2016-01-01

    , HOXA5, Chr1(q21.1).A, and Chr6(p22.1). In particular the OSR1, SIM1 and HOXB3/HOXB4 regions demonstrated high potential as biomarkers in LAC. For OSR1, hypermethylation was detected in 47/48 LAC cases compared to 1/31 tumor-adjacent normal lung samples. Similarly, 45/49 and 36/48 LAC cases compared...... patients by methylation-sensitive high resolution melting (MS-HRM) analysis. Significant increases in methylation were confirmed for 15 DMRs associated with the genes and genomic regions: OSR1, SIM1, GHSR, OTX2, LOC648987, HIST1H3E, HIST1H3G/HIST1H2BI, HIST1H2AJ/HIST1H2BM, HOXD10, HOXD3, HOXB3/HOXB4, HOXA3...... to 3/31 and 0/31 tumor-adjacent normal lung samples showed hypermethylation of the SIM1 and HOXB3/HOXB4 regions, respectively. In conclusion, this study has identified and validated 15 DMRs that can be targeted as biomarkers in LAC....

  14. Biomarkers of teratogenesis: suggestions from animal studies.

    Science.gov (United States)

    Giavini, Erminio; Menegola, Elena

    2012-09-01

    Biomarkers of effect are measurable biochemical, physiological or other alterations within an organism that can be recognized as causing an established or potential impairment of embryo-fetal development. They may be identified studying the mechanisms of action of teratogens. Hyperacetylation of histones, oxidative stress, cholesterol and retinoic acid unbalance are some of the identified mechanisms of action of some known teratogens. Nevertheless, their use is not currently applicable in human pregnancy because of the difficulty of the choice of biological material, the time when the material must be obtained, and the invasivity of methods. Furthermore, before using them in human pregnancy studies, biomarkers should be validated in experimental animals and in epidemiologic studies. On the contrary, some biomarkers could be useful in the screening of developmental toxicity of chemicals and drugs, comparing molecules of the same chemical class or with the similar pharmacologic activity, and using adequate in vitro tests, in order to reduce the use of experimental animals.

  15. Imaging biomarker roadmap for cancer studies

    Science.gov (United States)

    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, John 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; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

    2017-01-01

    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 drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing ‘translational gaps’ through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored ‘roadmap’. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use. PMID:27725679

  16. Current technological challenges in biomarker discovery and validation

    NARCIS (Netherlands)

    Horvatovich, Peter L.; Bischoff, Rainer

    2010-01-01

    In this review we will give an overview of the issues related to biomarker discovery studies with a focus on liquid chromatography-mass spectrometry (LC-MS) methods. Biomarker discovery is based on a close collaboration between clinicians, analytical scientists and chemometritians/statisticians. It

  17. Validation of Biomarkers for Prostate Cancer Prognosis

    Science.gov (United States)

    2015-11-01

    example the OncotypeDx assay has been calibrated and already validated precisely for this purpose. In addition, multiparametric MRI shows good ...testing. Cancer 119: 3906-3909, 2013. Zuxiong Chen, Zulfiqar G. Gulzar, Catherine A. St. Hill, Bruce Walcheck, James D. Brooks: Increased expression...Jamaspishvili T, Wei W, Feng Z, Good J, Hawley S, Fazli L, McKenney J, Simko J, Hurtado-Coll A, Carroll P, Gleave M, Lance R, Lin D, Nelson P, Thompson I

  18. Validation of Biomarkers of the Tumor Microenvironment

    Science.gov (United States)

    2015-10-01

    CONTRACTING ORGANIZATION: University of California Irvine, Ca 92697-4800 REPORT DATE: October 2015 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army...not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE ...14. ABSTRACT Currently the diagnosis of prostate cancer rests on the results of a biopsy . There are over one million biopsies performed in the U.S

  19. Validation of Biomarkers of the Tumor Microenvironment

    Science.gov (United States)

    2014-10-01

    anatomically negative biopsies. The methods that needed to be developed were PCR primers that operate on RNA retrieved from FFPE prostate cancer tissue and...biopsy tissue in order to validate the accuracy of a multigene stroma-based classifier for diagnosis of prostate cancer using anatomically negative...Canadian journal of urology 21, 14-21 7. Dorff, T. B., Flaig, T. W., Tangen, C. M., Hussain, M. H., Swanson, G. P., Wood , D. P., Jr., Sakr, W. A

  20. Improving Biomarker Development and Assessment: Standards for Study Design

    Institute of Scientific and Technical Information of China (English)

    Ziding FENG

    2009-01-01

    Background: The Early Detection Research Network (EDRN), NCI funded and investigator driven, has the mission to evaluate biomarkers for their clinical utilities in cancer risk prediction, diagnosis, early detection, and prognosis. Abundant cancer biomarkers reported in literature yet few are used in clinics. Therefore, the emphasis of the EDRN is biomarker validation. Although schema for a phased approach to development exists and guidelines are available for study reporting, a coherent and comprehensive set of guideline for a definitive biomarker validation study design have not been delineated.Methods: We proposed PROBE study design, Prospective specimen collec-tion and Retrospective Blinded Evaluation, for pivotal definitive evaluation of the accuracy of a classification biomarker. A detailed formulation of all aspects of the design is provided. Four tables itemize aspects that relate to (i) the Clinical Context; (ii) Performance Criteria; (iii) the Biomarker test; and (iv) Study power and termination. Alternative designs and strategies were contrasted to illustrate the merit of PROBE design.Results: The ideas are applied to studies of biomarkers the intended use of which is for disease diagnosis, screening, or prognosis. Two EDRN valida-tion studies (breast cancer and prostate cancer) were used as examples to elucidate PROBE design.Conclusion: Common biases that pervade the biomarker research literaturewould be eliminated if these rigorous standards were followed closely. We urge the adoption of the design as standard of practice for pivotal evaluation of the classification accuracy ofbiomarkers.

  1. Validation of beverage intake methods vs. hydration biomarker: a short review

    Directory of Open Access Journals (Sweden)

    Mariela Nissensohn

    2013-12-01

    Full Text Available Introduction: Fluid intake is difficult to monitor. Biomarkers of beverage intake are able to assess dietary intake / hydration status without the bias of self-reported dietary intake errors and also the intra-individual variability. Various markers have been proposed to assess hydration, however, to date; there is a lack of universally accepted biomarker that reflects changes of hydration status in response to changes in beverage intake. Aim: We conduct a review to find out the questionnaires of beverage intake available in the scientific literature to assess beverage intake and hydration status and their validation against hydration biomarkers. Methods: A scientific literature search was conducted. Only two articles were selected, in which, two different beverage intake questionnaires designed to capture the usual beverage intake were validated against Urine Specific Gravidity biomarker (Usg. Results: Water balance questionnaire (WBQ reported no correlations in the first study and the Beverage Intake Questionnaire (BEVQ, a quantitative Food frequency questionnaire (FFQ in the second study, also found a negative correlation. FFQ appears to measure better beverage intake than WBQ when compared with biomarkers. However, the WBQ seems to be a more complete method to evaluate the hydration balance of a given population. Conclusions: Further research is needed to understand the meaning of the different correlations between intake estimates and biomarkers of hydration in distinct population groups and environments.

  2. Validation of CBCT for the computation of textural biomarkers

    Science.gov (United States)

    Paniagua, Beatriz; Ruellas, Antonio C.; Benavides, Erika; Marron, Steve; Wolford, Larry; Cevidanes, Lucia

    2015-03-01

    Osteoarthritis (OA) is associated with significant pain and 42.6% of patients with TMJ disorders present with evidence of TMJ OA. However, OA diagnosis and treatment remain controversial, since there are no clear symptoms of the disease. The subchondral bone in the TMJ is believed to play a major role in the progression of OA. We hypothesize that the textural imaging biomarkers computed in high resolution Conebeam CT (hr- CBCT) and μCT scans are comparable. The purpose of this study is to test the feasibility of computing textural imaging biomarkers in-vivo using hr-CBCT, compared to those computed in μCT scans as our Gold Standard. Specimens of condylar bones obtained from condylectomies were scanned using μCT and hr- CBCT. Nine different textural imaging biomarkers (four co-occurrence features and five run-length features) from each pair of μCT and hr-CBCT were computed and compared. Pearson correlation coefficients were computed to compare textural biomarkers values of μCT and hr-CBCT. Four of the nine computed textural biomarkers showed a strong positive correlation between biomarkers computed in μCT and hr-CBCT. Higher correlations in Energy and Contrast, and in GLN (grey-level non-uniformity) and RLN (run length non-uniformity) indicate quantitative texture features can be computed reliably in hr-CBCT, when compared with μCT. The textural imaging biomarkers computed in-vivo hr-CBCT have captured the structure, patterns, contrast between neighboring regions and uniformity of healthy and/or pathologic subchondral bone. The ability to quantify bone texture non-invasively now makes it possible to evaluate the progression of subchondral bone alterations, in TMJ OA.

  3. Multicentric Validation of Proteomic Biomarkers in Urine Specific for Diabetic Nephropathy

    NARCIS (Netherlands)

    Alkhalaf, Alaa; Zurbig, Petra; Bakker, Stephan J. L.; Bilo, Henk J. G.; Cerna, Marie; Fischer, Christine; Fuchs, Sebastian; Janssen, Bart; Medek, Karel; Mischak, Harald; Roob, Johannes M.; Rossing, Kasper; Rossing, Peter; Rychlik, Ivan; Sourij, Harald; Tiran, Beate; Winklhofer-Roob, Brigitte M.; Navis, Gerjan J.

    2010-01-01

    Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respe

  4. Validity of biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes : a systematic review

    NARCIS (Netherlands)

    Hellemons, M. E.; Kerschbaum, J.; Bakker, S. J. L.; Neuwirt, H.; Mayer, B.; Mayer, G.; de Zeeuw, D.; Lambers Heerspink, H. J.; Rudnicki, M.

    2012-01-01

    Novel biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes have been recently identified. We performed a systematic review to assess the validity of biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes in longitudinal studie

  5. Targeted discovery and validation of plasma biomarkers of Parkinson's disease.

    Science.gov (United States)

    Pan, Catherine; Zhou, Yong; Dator, Romel; Ginghina, Carmen; Zhao, Yanchun; Movius, James; Peskind, Elaine; Zabetian, Cyrus P; Quinn, Joseph; Galasko, Douglas; Stewart, Tessandra; Shi, Min; Zhang, Jing

    2014-11-07

    Despite extensive research, an unmet need remains for protein biomarkers of Parkinson's disease (PD) in peripheral body fluids, especially blood, which is easily accessible clinically. The discovery of such biomarkers is challenging, however, due to the enormous complexity and huge dynamic range of human blood proteins, which are derived from nearly all organ systems, with those originating specifically from the central nervous system (CNS) being exceptionally low in abundance. In this investigation of a relatively large cohort (∼300 subjects), selected reaction monitoring (SRM) assays (a targeted approach) were used to probe plasma peptides derived from glycoproteins previously found to be altered in the CNS based on PD diagnosis or severity. Next, the detected peptides were interrogated for their diagnostic sensitivity and specificity as well as the correlation with PD severity, as determined by the Unified Parkinson's Disease Rating Scale (UPDRS). The results revealed that 12 of the 50 candidate glycopeptides were reliably and consistently identified in plasma samples, with three of them displaying significant differences among diagnostic groups. A combination of four peptides (derived from PRNP, HSPG2, MEGF8, and NCAM1) provided an overall area under curve (AUC) of 0.753 (sensitivity: 90.4%; specificity: 50.0%). Additionally, combining two peptides (derived from MEGF8 and ICAM1) yielded significant correlation with PD severity, that is, UPDRS (r = 0.293, p = 0.004). The significance of these results is at least two-fold: (1) it is possible to use a targeted approach to identify otherwise very difficult to detect CNS related biomarkers in peripheral blood and (2) the novel biomarkers, if validated in independent cohorts, can be employed to assist with clinical diagnosis of PD as well as monitoring disease progression.

  6. Validated biomarkers: The key to precision treatment in patients with breast cancer.

    Science.gov (United States)

    Duffy, Michael J; O'Donovan, Norma; McDermott, Enda; Crown, John

    2016-10-01

    Recent DNA sequencing and gene expression studies have shown that at a molecular level, almost every case of breast cancer is unique and different from other breast cancers. For optimum management therefore, every patient should receive treatment that is guided by the molecular composition of their tumor, i.e., precision treatment. While such a scenario is still some distance into the future, biomarkers are beginning to play an important role in preparing the way for precision treatment. In particular, biomarkers are increasingly being used for predicting patient outcome and informing as to the most appropriate type of systemic therapy to be administered. Mandatory biomarkers for every newly diagnosed case of breast cancer are estrogen receptors and progesterone receptors in selecting patients for endocrine treatment and HER2 for identifying patients likely to benefit from anti-HER2 therapy. Amongst the best validated prognostic biomarker tests are uPA/PAI-1, MammaPrint and Oncotype DX. Although currently, there are no biomarkers available for predicting response to specific forms of chemotherapy, uPA/PAI-1 and Oncotype DX can aid the identification of lymph node-negative patients that are most likely to benefit from adjuvant chemotherapy, in general. In order to accelerate progress towards precision treatment for women with breast cancer, we need additional predictive biomarkers, especially for enhancing the positive predictive value for endocrine and anti-HER2 therapies, as well as biomarkers for predicting response to specific forms of chemotherapy. The ultimate biomarker test for achieving the goal of precision treatment for patients with breast cancer will likely require a combination of gene sequencing and transcriptomic analysis of every patient's tumor.

  7. Strategies for discovery and validation of methylated and hydroxymethylated DNA biomarkers.

    Science.gov (United States)

    Olkhov-Mitsel, Ekaterina; Bapat, Bharati

    2012-10-01

    DNA methylation, consisting of the addition of a methyl group at the fifth-position of cytosine in a CpG dinucleotide, is one of the most well-studied epigenetic mechanisms in mammals with important functions in normal and disease biology. Disease-specific aberrant DNA methylation is a well-recognized hallmark of many complex diseases. Accordingly, various studies have focused on characterizing unique DNA methylation marks associated with distinct stages of disease development as they may serve as useful biomarkers for diagnosis, prognosis, prediction of response to therapy, or disease monitoring. Recently, novel CpG dinucleotide modifications with potential regulatory roles such as 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine have been described. These potential epigenetic marks cannot be distinguished from 5-methylcytosine by many current strategies and may potentially compromise assessment and interpretation of methylation data. A large number of strategies have been described for the discovery and validation of DNA methylation-based biomarkers, each with its own advantages and limitations. These strategies can be classified into three main categories: restriction enzyme digestion, affinity-based analysis, and bisulfite modification. In general, candidate biomarkers are discovered using large-scale, genome-wide, methylation sequencing, and/or microarray-based profiling strategies. Following discovery, biomarker performance is validated in large independent cohorts using highly targeted locus-specific assays. There are still many challenges to the effective implementation of DNA methylation-based biomarkers. Emerging innovative methylation and hydroxymethylation detection strategies are focused on addressing these gaps in the field of epigenetics. The development of DNA methylation- and hydroxymethylation-based biomarkers is an exciting and rapidly evolving area of research that holds promise for potential applications in diverse clinical

  8. Identification and validation of urinary metabolite biomarkers for major depressive disorder.

    Science.gov (United States)

    Zheng, Peng; Wang, Ying; Chen, Liang; Yang, Deyu; Meng, Huaqing; Zhou, Dezhi; Zhong, Jiaju; Lei, Yang; Melgiri, N D; Xie, Peng

    2013-01-01

    Major depressive disorder (MDD) is a widespread and debilitating mental disorder. However, there are no biomarkers available to aid in the diagnosis of this disorder. In this study, a nuclear magnetic resonance spectroscopy-based metabonomic approach was employed to profile urine samples from 82 first-episode drug-naïve depressed subjects and 82 healthy controls (the training set) in order to identify urinary metabolite biomarkers for MDD. Then, 44 unselected depressed subjects and 52 healthy controls (the test set) were used to independently validate the diagnostic generalizability of these biomarkers. A panel of five urinary metabolite biomarkers-malonate, formate, N-methylnicotinamide, m-hydroxyphenylacetate, and alanine-was identified. This panel was capable of distinguishing depressed subjects from healthy controls with an area under the receiver operating characteristic curve (AUC) of 0.81 in the training set. Moreover, this panel could classify blinded samples from the test set with an AUC of 0.89. These findings demonstrate that this urinary metabolite biomarker panel can aid in the future development of a urine-based diagnostic test for MDD.

  9. Potentials of single-cell biology in identification and validation of disease biomarkers.

    Science.gov (United States)

    Niu, Furong; Wang, Diane C; Lu, Jiapei; Wu, Wei; Wang, Xiangdong

    2016-09-01

    Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location. We headline the important role of single-cell biology in the discovery and development of disease-specific biomarkers with a special emphasis on understanding single-cell biological functions, e.g. mechanical phenotypes, single-cell biology, heterogeneity and organization of genome function. We have reason to believe that such multi-dimensional, multi-layer, multi-crossing and stereoscopic single-cell biology definitely benefits the discovery and development of disease-specific biomarkers.

  10. Validation of Candidate Serum Ovarian Cancer Biomarkers for Early Detection

    Directory of Open Access Journals (Sweden)

    Feng Su

    2007-01-01

    Full Text Available Objective: We have previously analyzed protein profi les using Surface Enhanced Laser Desorption and Ionization Time-Of-Flight Mass Spectroscopy (SELDI-TOF-MS [Kozak et al. 2003, Proc. Natl. Acad. Sci. U.S.A. 100:12343–8] and identified 3 differentially expressed serum proteins for the diagnosis of ovarian cancer (OC [Kozak et al. 2005, Proteomics, 5:4589–96], namely, apolipoprotein A-I (apoA-I, transthyretin (TTR and transferin (TF. The objective of the present study is to determine the efficacy of the three OC biomarkers for the detection of early stage (ES OC, in direct comparison to CA125.Methods: The levels of CA125, apoA-I, TTR and TF were measured in 392 serum samples [82 women with normal ovaries (N, 24 women with benign ovarian tumors (B, 85 women with ovarian tumors of low malignant potential (LMP, 126 women with early stage ovarian cancer (ESOC, and 75 women with late stage ovarian cancer (LSOC], obtained through the GOG and Cooperative Human Tissue Network. Following statistical analysis, multivariate regression models were built to evaluate the utility of the three OC markers in early detection.Results: Multiple logistic regression models (MLRM utilizing all biomarker values (CA125, TTR, TF and apoA-I from all histological subtypes (serous, mucinous, and endometrioid adenocarcinoma distinguished normal samples from LMP with 91% sensitivity (specifi city 92%, and normal samples from ESOC with a sensitivity of 89% (specifi city 92%. MLRM, utilizing values of all four markers from only the mucinous histological subtype showed that collectively, CA125, TTR, TF and apoA-I, were able to distinguish normal samples from mucinous LMP with 90% sensitivity, and further distinguished normal samples from early stage mucinous ovarian cancer with a sensitivity of 95%. In contrast, in serum samples from patients with mucinous tumors, CA125 alone was able to distinguish normal samples from LMP and early stage ovarian cancer with a sensitivity of

  11. Statistical design and evaluation of biomarker studies.

    Science.gov (United States)

    Dobbin, Kevin K

    2014-01-01

    We review biostatistical aspects of biomarker studies, including design and analysis issues, covering the range of settings required for translational research-from early exploratory studies through clinical trials.

  12. Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening.

    Directory of Open Access Journals (Sweden)

    Michael Phillips

    Full Text Available Breath volatile organic compounds (VOCs have been reported as biomarkers of lung cancer, but it is not known if biomarkers identified in one group can identify disease in a separate independent cohort. Also, it is not known if combining breath biomarkers with chest CT has the potential to improve the sensitivity and specificity of lung cancer screening.Model-building phase (unblinded: Breath VOCs were analyzed with gas chromatography mass spectrometry in 82 asymptomatic smokers having screening chest CT, 84 symptomatic high-risk subjects with a tissue diagnosis, 100 without a tissue diagnosis, and 35 healthy subjects. Multiple Monte Carlo simulations identified breath VOC mass ions with greater than random diagnostic accuracy for lung cancer, and these were combined in a multivariate predictive algorithm. Model-testing phase (blinded validation: We analyzed breath VOCs in an independent cohort of similar subjects (n = 70, 51, 75 and 19 respectively. The algorithm predicted discriminant function (DF values in blinded replicate breath VOC samples analyzed independently at two laboratories (A and B. Outcome modeling: We modeled the expected effects of combining breath biomarkers with chest CT on the sensitivity and specificity of lung cancer screening.Unblinded model-building phase. The algorithm identified lung cancer with sensitivity 74.0%, specificity 70.7% and C-statistic 0.78. Blinded model-testing phase: The algorithm identified lung cancer at Laboratory A with sensitivity 68.0%, specificity 68.4%, C-statistic 0.71; and at Laboratory B with sensitivity 70.1%, specificity 68.0%, C-statistic 0.70, with linear correlation between replicates (r = 0.88. In a projected outcome model, breath biomarkers increased the sensitivity, specificity, and positive and negative predictive values of chest CT for lung cancer when the tests were combined in series or parallel.Breath VOC mass ion biomarkers identified lung cancer in a separate independent cohort

  13. Early-Phase Studies of Biomarkers

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Many cancer biomarker research studies seek to develop markers that can accurately detect or predict future onset of disease. To design and evaluate these studies, one must specify the levels of accuracy sought. However, justified target levels are rarely available. METHODS: We describe...... a way to calculate target levels of sensitivity and specificity for a biomarker intended to be applied in a defined clinical context. The calculation requires knowledge of the prevalence or incidence of cases in the clinical population and the ratio of benefit associated with the clinical consequences...... 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...

  14. The Integrated Oncology Program of the Italian Ministry of Health. Analytical and clinical validation of new biomarkers for early diagnosis: network, resources, methodology, quality control, and data analysis.

    Science.gov (United States)

    Paradiso, Angelo; Mangia, Anita; Orlando, Claudio; Verderio, Paolo; Belfiglio, Maurizio; Marchetti, Antonio; Bertario, Lucio; Chiappetta, Gennaro; Gion, Massimo; Tonini, Gian Paolo; Podo, Franca; Vocaturo, Amina; Silvestrini, Rosella; Romani, Massimo; Belloni, Elena; Cavallo, Delia; Ulivi, Paola; Tommasi, Stefania; Steffan, Agostino; Russo, Antonio; Alessio, Massimo; Calistri, Daniele; Zancan, Matelda; Parrela, Paola; Broggini, Massimo; Giuseppe, Antonio; Buttitta, Fiamma; Finocchiaro, Gaetano; Mazzocco, Katia; Veronesi, Giulia; Landuzzi, Lorena; Benevolo, Maria; Mariani, Luciano; De Marco, Federico; Venuti, Aldo; Giannelli, Gianluigi; Quaranta, Michele; Trojano, Vito

    2009-01-01

    In 2007, an Italian cancer research group proposed a specific concerted action aimed at the "analytical and clinica validation of new biomarkers for early diagnosis: Network, resources, methodology, quality control, and data analysis." The proposal united 37 national operative units involved in different biomarker studies and it created a strong coordinative body with the necessary expertise in methodologies, statistical analysis, quality control, and biological resources to perform ad hoc validation studies for new biomarkers of early cancer diagnosis. The action, financed by the Italian Ministry of Health within the Integrated Oncology Program (PIO) coordinated by NCI-Istituto Tumori Bari, started in 2007 and activated 7 projects, each of which focused on disease-specific biomarker studies. Overall, the 37 participating units proposed studies on 50 biomarkers, including analytical and clinical validation procedures. Clusters of units were specifically involved in research of early-detection biomarkers for cancers of the lung, digestive tract, prostate/bladder, and nervous system, as well as female cancers. Furthermore, a cluster involved in biomarkers for bioimaging and infection-related cancers was created. The first investigators' meeting, "Analytical and clinical validation of new biomarkers for early diagnosis," was held on 9 September 2008 in Bari. During this meeting, methodological aspects, scientific programs and preliminary results were presented and discussed.

  15. Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes.

    Directory of Open Access Journals (Sweden)

    Barbara Stefanska

    Full Text Available Poor prognosis of hepatocellular carcinoma (HCC associated with late diagnosis necessitates the development of early diagnostic biomarkers. We have previously delineated the landscape of DNA methylation in HCC patients unraveling the importance of promoter hypomethylation in activation of cancer- and metastasis-driving genes. The purpose of the present study was to test the feasibility that genes that are hypomethylated in HCC could serve as candidate diagnostic markers. We use high resolution melting analysis (HRM as a simple translatable PCR-based method to define methylation states in clinical samples. We tested seven regions selected from the shortlist of genes hypomethylated in HCC and showed that HRM analysis of several of them distinguishes methylation states in liver cancer specimens from normal adjacent liver and chronic hepatitis in the Shanghai area. Such regions were identified within promoters of neuronal membrane glycoprotein M6-B (GPM6B and melanoma antigen family A12 (MAGEA12 genes. Differences in HRM in the immunoglobulin superfamily Fc receptor (FCRL1 separated invasive tumors from less invasive HCC. The identified biomarkers differentiated HCC from chronic hepatitis in another set of samples from Dhaka. Although the main thrust in DNA methylation diagnostics in cancer is on hypermethylated genes, our study for the first time illustrates the potential use of hypomethylated genes as markers for solid tumors. After further validation in a larger cohort, the identified DNA hypomethylated regions can become important candidate biomarkers for liver cancer diagnosis and prognosis, especially in populations with high risk for HCC development.

  16. Validation of plasma microRNAs as biomarkers for myotonic dystrophy type 1

    Science.gov (United States)

    Perfetti, A.; Greco, S.; Cardani, R.; Fossati, B.; Cuomo, G.; Valaperta, R.; Ambrogi, F.; Cortese, A.; Botta, A.; Mignarri, A.; Santoro, M.; Gaetano, C.; Costa, E.; Dotti, M. T.; Silvestri, G.; Massa, R.; Meola, G.; Martelli, F.

    2016-01-01

    Non-invasive and simple to measure biomarkers are still an unmet need for myotonic dystrophy type 1 (DM1). Indeed, muscle biopsies can be extremely informative, but their invasive nature limits their application. Extracellular microRNAs are emerging humoral biomarkers and preliminary studies identified a group of miRNAs that are deregulated in the plasma or serum of small groups of DM1 patients. Here we adopted very stringent selection and normalization criteria to validate or disprove these miRNAs in 103 DM1 patients and 111 matched controls. We confirmed that 8 miRNAs out of 12 were significantly deregulated in DM1 patients: miR-1, miR-27b, miR-133a, miR-133b, miR-206, miR-140-3p, miR-454 and miR-574. The levels of these miRNAs, alone or in combination, discriminated DM1 from controls significantly, and correlated with both skeletal muscle strength and creatine kinase values. Interestingly, miR-133b levels were significantly higher in DM1 female patients. Finally, the identified miRNAs were also deregulated in the plasma of a small group (n = 30) of DM2 patients. In conclusion, this study proposes that miRNAs might be useful as DM1 humoral biomarkers. PMID:27905532

  17. Sterol and genomic analyses validate the sponge biomarker hypothesis.

    Science.gov (United States)

    Gold, David A; Grabenstatter, Jonathan; de Mendoza, Alex; Riesgo, Ana; Ruiz-Trillo, Iñaki; Summons, Roger E

    2016-03-01

    Molecular fossils (or biomarkers) are key to unraveling the deep history of eukaryotes, especially in the absence of traditional fossils. In this regard, the sterane 24-isopropylcholestane has been proposed as a molecular fossil for sponges, and could represent the oldest evidence for animal life. The sterane is found in rocks ∼650-540 million y old, and its sterol precursor (24-isopropylcholesterol, or 24-ipc) is synthesized today by certain sea sponges. However, 24-ipc is also produced in trace amounts by distantly related pelagophyte algae, whereas only a few close relatives of sponges have been assayed for sterols. In this study, we analyzed the sterol and gene repertoires of four taxa (Salpingoeca rosetta, Capsaspora owczarzaki, Sphaeroforma arctica, and Creolimax fragrantissima), which collectively represent the major living animal outgroups. We discovered that all four taxa lack C30 sterols, including 24-ipc. By building phylogenetic trees for key enzymes in 24-ipc biosynthesis, we identified a candidate gene (carbon-24/28 sterol methyltransferase, or SMT) responsible for 24-ipc production. Our results suggest that pelagophytes and sponges independently evolved C30 sterol biosynthesis through clade-specific SMT duplications. Using a molecular clock approach, we demonstrate that the relevant sponge SMT duplication event overlapped with the appearance of 24-isopropylcholestanes in the Neoproterozoic, but that the algal SMT duplication event occurred later in the Phanerozoic. Subsequently, pelagophyte algae and their relatives are an unlikely alternative to sponges as a source of Neoproterozoic 24-isopropylcholestanes, consistent with growing evidence that sponges evolved long before the Cambrian explosion ∼542 million y ago.

  18. Identification and Validation of Plasma Biomarkers in California Sea Lions

    Science.gov (United States)

    2014-04-24

    Final 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) Office of Naval Research 100 Alabama St. SW Suite4R15 Atlanta, GA 30303-3104 10...enable the Navy marine mammal program to screen animals for DAT. Several proteomic approaches were utilized and data were modeled using neural...biomarkers using investigator-blinded plasma samples from The Marine Mammal Center. 3. Assess the performance of MALDI-ToF mass spectrometry

  19. Computational protein biomarker prediction: a case study for prostate cancer

    Directory of Open Access Journals (Sweden)

    Adam Bao-Ling

    2004-03-01

    Full Text Available Abstract Background Recent technological advances in mass spectrometry pose challenges in computational mathematics and statistics to process the mass spectral data into predictive models with clinical and biological significance. We discuss several classification-based approaches to finding protein biomarker candidates using protein profiles obtained via mass spectrometry, and we assess their statistical significance. Our overall goal is to implicate peaks that have a high likelihood of being biologically linked to a given disease state, and thus to narrow the search for biomarker candidates. Results Thorough cross-validation studies and randomization tests are performed on a prostate cancer dataset with over 300 patients, obtained at the Eastern Virginia Medical School using SELDI-TOF mass spectrometry. We obtain average classification accuracies of 87% on a four-group classification problem using a two-stage linear SVM-based procedure and just 13 peaks, with other methods performing comparably. Conclusions Modern feature selection and classification methods are powerful techniques for both the identification of biomarker candidates and the related problem of building predictive models from protein mass spectrometric profiles. Cross-validation and randomization are essential tools that must be performed carefully in order not to bias the results unfairly. However, only a biological validation and identification of the underlying proteins will ultimately confirm the actual value and power of any computational predictions.

  20. Recommendations for adaptation and validation of commercial kits for biomarker quantification in drug development.

    Science.gov (United States)

    Khan, Masood U; Bowsher, Ronald R; Cameron, Mark; Devanarayan, Viswanath; Keller, Steve; King, Lindsay; Lee, Jean; Morimoto, Alyssa; Rhyne, Paul; Stephen, Laurie; Wu, Yuling; Wyant, Timothy; Lachno, D Richard

    2015-01-01

    Increasingly, commercial immunoassay kits are used to support drug discovery and development. Longitudinally consistent kit performance is crucial, but the degree to which kits and reagents are characterized by manufacturers is not standardized, nor are the approaches by users to adapt them and evaluate their performance through validation prior to use. These factors can negatively impact data quality. This paper offers a systematic approach to assessment, method adaptation and validation of commercial immunoassay kits for quantification of biomarkers in drug development, expanding upon previous publications and guidance. These recommendations aim to standardize and harmonize user practices, contributing to reliable biomarker data from commercial immunoassays, thus, enabling properly informed decisions during drug development.

  1. Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Alaa Alkhalaf

    Full Text Available BACKGROUND: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN, urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration ≥5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66. Controls were matched for gender and diabetes duration (n = 82. METHODOLOGY/PRINCIPAL FINDINGS: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS. Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978. Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. CONCLUSIONS: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin.

  2. Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Richard J Perrin

    Full Text Available Ideally, disease modifying therapies for Alzheimer disease (AD will be applied during the 'preclinical' stage (pathology present with cognition intact before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1 (n = 24 and cognitively normal controls (CDR 0 (n = 24 were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA. Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs to a larger independent cohort (n = 292 that included individuals with very mild dementia (CDR 0.5. Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI] and 0.88 (0.81-0.94 CI, respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding

  3. Biomarker Validation for Aging: Lessons from mtDNA Heteroplasmy Analyses in Early Cancer Detection

    Directory of Open Access Journals (Sweden)

    Peter E. Barker

    2009-11-01

    Full Text Available The anticipated biological and clinical utility of biomarkers has attracted significant interest recently. Aging and early cancer detection represent areas active in the search for predictive and prognostic biomarkers. While applications differ, overlapping biological features, analytical technologies and specific biomarker analytes bear comparison. Mitochondrial DNA (mtDNA as a biomarker in both biological models has been evaluated. However, it remains unclear whether mtDNA changes in aging and cancer represent biological relationships that are causal, incidental, or a combination of both. This article focuses on evaluation of mtDNA-based biomarkers, emerging strategies for quantitating mtDNA admixtures, and how current understanding of mtDNA in aging and cancer evolves with introduction of new technologies. Whether for cancer or aging, lessons from mtDNA based biomarker evaluations are several. Biological systems are inherently dynamic and heterogeneous. Detection limits for mtDNA sequencing technologies differ among methods for low-level DNA sequence admixtures in healthy and diseased states. Performance metrics of analytical mtDNA technology should be validated prior to application in heterogeneous biologically-based systems. Critical in evaluating biomarker performance is the ability to distinguish measurement system variance from inherent biological variance, because it is within the latter that background healthy variability as well as high-value, disease-specific information reside.

  4. Validity of multiplex biomarker model of 6 genes for the differential diagnosis of thyroid nodules

    Directory of Open Access Journals (Sweden)

    Ducena Kristine

    2011-06-01

    Full Text Available Abstract Background Currently the cytological examination of fine needle aspiration (FNA biopsies is the standard technique for the pre-operative differential diagnosis of thyroid nodules. However, the results may be non-informative in ~20% of cases due to an inadequate sampling and the lack of highly specific, measurable cytological criteria, therefore ancillary biomarkers that could aid in these cases are clearly needed. The aim of our study was to evaluate the mRNA expression levels of 8 candidate marker genes as the diagnostic biomarkers for the discrimination of benign and malignant thyroid nodules and to find a combination of biomarkers with the highest diagnostic value. Materials and methods mRNA expression levels of eight candidate marker genes - BIRC5, CCND1, CDH1, CITED1, DPP4, LGALS3, MET and TFF3 was measured by real-time RT-PCR in paired nodular and surrounding normal thyroid tissue specimens of 105 consecutive patients undergoing thyroid surgery and compared between different types of thyroid lesions. Results Significant differences in the mRNA expression levels between the normal and malignant thyroid tissues and between benign and malignant nodules were found for BIRC5, CCND1, CITED1, DPP4, LGALS3, MET and TFF3, but not CDH1. On a single gene basis, relative quantity (RQ of LGALS3 had the highest diagnostic value for the discrimination of malignant and benign thyroid nodules (AUC = 0.832, P LGALS3 was RQ sum of LGALS3 and BIRC5 (AUC = 0.841, P LGALS3, BIRC5, TFF3, CCND1, MET and CITED1 that had considerably higher specificity than a single marker or two marker gene-based models (AUC = 0.895, P Conclusions This study confirmed that mRNA expression levels of 7 out of 8 candidate genes analysed have a diagnostic value for the distinction of benign and malignant thyroid nodules. The multiplex biomarker model based on 6 genes outperformed a single marker or two marker-based models and warrants feasibility studies on FNA biopsies and

  5. Validation of trichloroacetic acid exposure via drinking water during pregnancy using a urinary TCAA biomarker.

    Science.gov (United States)

    Smith, Rachel B; Nieuwenhuijsen, Mark J; Wright, John; Raynor, Pauline; Cocker, John; Jones, Kate; Kappaostopoulou-Karadanelli, Maria; Toledano, Mireille B

    2013-10-01

    Disinfection by-product (DBP) exposure during pregnancy may be related to reduced fetal growth, but the evidence is inconclusive and improved DBP exposure assessment is required. The authors conducted a nested exposure study on a subset (n=39) of pregnant women in the Born in Bradford cohort to assess validity of TCAA exposure assessment based on tap water sampling and self-reported water-use; water-use questionnaire validity; and use of a one-time urinary TCAA biomarker. TCAA levels in urine and home tap water supply were quantified, and water use was measured via a questionnaire and 7-day diary, at 28 weeks gestation. Diary and urine measures were repeated later in pregnancy (n=14). TCAA level in home tap water supply was not correlated with urinary TCAA (0.18, P=0.29). Cold unfiltered tap water intake at home measured by questionnaire was correlated with urinary TCAA (0.44, P=0.007), but correlation was stronger still for cold unfiltered tap water intake reported over the 3 days prior to urine sampling (0.60, Pwater sampling and self-reported water-use, correlated strongly with urinary TCAA (0.78, Pwater intake is most influential in determining TCAA exposure variability in this cohort, and that TCAA ingestion at home is a valid proxy for TCAA exposure for unemployed women but less satisfactory for employed women.

  6. Neuroimaging as a biomarker in symptom validity and performance validity testing.

    Science.gov (United States)

    Bigler, Erin D

    2015-09-01

    How neuropsychological assessment findings are deemed valid has been a topic of numerous articles but few have addressed any role that neuroimaging studies could provide. Within military and various clinical samples of individuals undergoing neuropsychological evaluations, high levels of failure on measures of symptom validity testing (SVT) and/or performance validity testing (PVT) have been reported. Where 'failure' is defined as a below cut-score performance on some pre-determined set-point on a SVT/PVT measure, are such failures always indicative of invalid test findings or are there other explanations, especially based on informative neuroimaging findings? This review starts with the premise that even though the SVT/PVT task is designed to be simple and easy to perform, it nonetheless requires intact frontoparietal attention, working memory and task engagement (motivation) networks. If there is damage or pathology within any aspect of these networks as demonstrated by neuroimaging findings, the patient may perform below the cut-point as a result of the underlying damage or pathophysiology. The argument is made that neuroimaging findings should be considered as to where SVT/PVT cut-points are established and there should be much greater flexibility in SVT/PVT measures based on other personal, demographic and neuroimaging information. Several case studies are used to demonstrate these points.

  7. 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

    2013-11-15

    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.

  8. Analytical validation considerations of multiplex mass-spectrometry-based proteomic platforms for measuring protein biomarkers.

    Science.gov (United States)

    Boja, Emily S; Fehniger, Thomas E; Baker, Mark S; Marko-Varga, György; Rodriguez, Henry

    2014-12-01

    Protein biomarker discovery and validation in current omics era are vital for healthcare professionals to improve diagnosis, detect cancers at an early stage, identify the likelihood of cancer recurrence, stratify stages with differential survival outcomes, and monitor therapeutic responses. The success of such biomarkers would have a huge impact on how we improve the diagnosis and treatment of patients and alleviate the financial burden of healthcare systems. In the past, the genomics community (mostly through large-scale, deep genomic sequencing technologies) has been steadily improving our understanding of the molecular basis of disease, with a number of biomarker panels already authorized by the U.S. Food and Drug Administration (FDA) for clinical use (e.g., MammaPrint, two recently cleared devices using next-generation sequencing platforms to detect DNA changes in the cystic fibrosis transmembrane conductance regulator (CFTR) gene). Clinical proteomics, on the other hand, albeit its ability to delineate the functional units of a cell, more likely driving the phenotypic differences of a disease (i.e., proteins and protein-protein interaction networks and signaling pathways underlying the disease), "staggers" to make a significant impact with only an average ∼ 1.5 protein biomarkers per year approved by the FDA over the past 15-20 years. This statistic itself raises the concern that major roadblocks have been impeding an efficient transition of protein marker candidates in biomarker development despite major technological advances in proteomics in recent years.

  9. Testing of the OMERACT 8 draft validation criteria for a soluble biomarker reflecting structural damage in rheumatoid arthritis: a systematic literature search on 5 candidate biomarkers

    DEFF Research Database (Denmark)

    Syversen, Silje W; Landewe, Robert; van der Heijde, Désirée;

    2009-01-01

    OBJECTIVE: To test the OMERACT 8 draft validation criteria for soluble biomarkers by assessing the strength of literature evidence in support of 5 candidate biomarkers. METHODS: A systematic literature search was conducted on the 5 soluble biomarkers RANKL, osteoprotegerin (OPG), matrix...... metalloprotease (MMP-3), urine C-telopeptide of types I and II collagen (U-CTX-I and U CTX-II), focusing on the 14 OMERACT 8 criteria. Two electronic voting exercises were conducted to address: (1) strength of evidence for each biomarker as reflecting structural damage according to each individual criterion...... and the importance of each individual criterion; (2) overall strength of evidence in support of each of the 5 candidate biomarkers as reflecting structural damage endpoints in rheumatoid arthritis (RA) and identification of omissions to the criteria set. RESULTS: The search identified 111 articles. The strength...

  10. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

    Science.gov (United States)

    2015-10-01

    biomarkers to determine the presence of or progression to aggressive disease. ( Lead site: FHCRC) Milestone 2. Execute collaboration agreement with...panel of four-kallikrein plasma-based markers to determine the presence of or progression to clinically relevant prostate cancer. ( Lead site: FHCRC... Lead site: FHCRC) Milestone 10. Urine specimens identified for analysis. Due 12/30/2014 COMPLETED Milestone 11. PCA3 and TMPRSS2:ERG validation

  11. Validation of APF as a Urinary Biomarker for Interstitial Cystitis

    Science.gov (United States)

    2014-10-01

    compatible with IATA regulations as well as other protocol-related supplies to be used at each study site. A standard operating procedure was also...were generated by PCR and subcloned into the pET15b bacterial expression vector. All of the mutants (tagged at N-terminus with His6) were expressed...infectious substances (IATA and DOT) certification for appropriate personnel. • Procured shipping supplies for clinical specimens that are compatible

  12. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to d...

  13. A Novel Point-of-Care Biomarker Recognition Method: Validation by Detecting Marker for Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Sahana Pentyala

    2015-04-01

    Full Text Available Biological fluid collection to identify and analyze different disease markers is a routine and normal procedure in health care settings. Body fluids are as varied as urine, blood, mucus, cerebrospinal fluid (CSF, tears, semen, etc. The volumes of the collected fluids range from micro liters (e.g., tears, CSF to tens and hundreds of milliliters (blood, urine, etc.. In some manifestations, a disease marker (particularly protein markers can occur in trace amounts, yet the fluids collected are in large volumes. To identify these trace markers, cumbersome methods, expensive instruments, and trained personnel are required. We developed an easy method to rapidly capture, concentrate, and identify protein markers in large volumes of test fluids. This method involves the utilization of two antibodies recognizing two different epitopes of the protein biomarker. Antibody-1 helps to capture and concentrate the biomarker and Antibody-2 adsorbed or conjugated to nanogold beads will detect the biomarker. This method was validated in capturing and detecting lipocalin type prostaglandin-D2 synthase, a marker in urine that implicates diabetic nephropathy. A one-step collection, concentration, and detection device was designed based on this method. This device can replace many of the normal body fluid collection devices such as tubes and containers. A one-step fluid collection and biomarker capture and concentration device for rapid diagnosis of diseases has tremendous advantage in terms of cost and providing timely results.

  14. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...... endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...

  15. 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.

  16. Cerebrospinal Fluid Biomarkers in Spinocerebellar Ataxia: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Ashley M. Brouillette

    2015-01-01

    Full Text Available Neurodegenerative diseases, including the spinocerebellar ataxias (SCA, would benefit from the identification of reliable biomarkers that could serve as disease subtype-specific and stage-specific indicators for the development and monitoring of treatments. We analyzed the cerebrospinal fluid (CSF level of tau, α-synuclein, DJ-1, and glial fibrillary acidic protein (GFAP, proteins previously associated with neurodegenerative processes, in patients with the autosomal dominant SCA1, SCA2, and SCA6, and the sporadic disease multiple system atrophy, cerebellar type (MSA-C, compared with age-matched controls. We estimated disease severity using the Scale for the Assessment and Rating of Ataxia (SARA. Most proteins measured trended higher in disease versus control group yet did not reach statistical significance. We found the levels of tau in both SCA2 and MSA-C patients were significantly higher than control. We found that α-synuclein levels were lower with higher SARA scores in SCA1 and tau levels were higher with greater SARA in MSA-C, although this final correlation did not reach statistical significance after post hoc correction. Additional studies with larger sample sizes are needed to improve the power of these studies and validate the use of CSF biomarkers in SCA and MSA-C.

  17. Use of a food frequency questionnaire to assess diets of Jamaican adults: validation and correlation with biomarkers

    Directory of Open Access Journals (Sweden)

    Younger Novie M

    2011-04-01

    Full Text Available Abstract Background Assessment of habitual diet is important in investigations of diet-disease relationships. Many epidemiological studies use the food frequency questionnaire (FFQ to evaluate dietary intakes but few studies validate the instrument against biological markers. The aim of this study was to assess the validity and reproducibility of a previously validated 70-item food frequency questionnaire (FFQ that was expanded to 120-items to assess diet - cancer relations. Methods Relative validity of the FFQ was assessed against twelve 24-hour recalls administered over 12 months in 70 subjects. The FFQ was repeated after one year (FFQ2 to assess reproducibility. The validity of the FFQ was evaluated by comparing nutrient and food group intakes from 24-hour recalls with the first and second FFQ. In addition, FFQ validity for cholesterol and folate were determined through correlation with biomarkers (serum cholesterol, serum folate and whole blood folate in 159 control subjects participating in a case-control prostate cancer study. Results Compared to recalls the FFQ tended to overestimate energy and carbohydrate intakes but gave no differences in intake for protein and fat. Quartile agreement for energy-adjusted nutrient intakes between FFQ2 and recalls ranged from 31.8% - 77.3% for the lowest quartile and 20.8% - 81.0% in the highest quartile. Gross misclassification of nutrients was low with the exceptions of protein, vitamin E and retinol and weighted kappa values ranged from 0.33 to 0.64 for other nutrients. Validity correlations for energy-adjusted nutrients (excluding retinol were moderate to high (0.38- 0.86. Correlation coefficients between multiple recalls and FFQ1 ranged from 0.27 (fruits to 0.55 (red meat; the second FFQ gave somewhat higher coefficients (0.30 to 0.61. Reproducibility correlations for the nutrients ranged from 0.50 to 0.84. Calibration of the FFQ with biochemical markers showed modest correlations with serum

  18. Neuro-imaging the serotonin 2A receptor as a valid biomarker for canine behavioural disorders.

    Science.gov (United States)

    Vermeire, Simon; Audenaert, Kurt; De Meester, Rudy; Vandermeulen, Eva; Waelbers, Tim; De Spiegeleer, Bart; Eersels, Jos; Dobbeleir, André; Peremans, Kathelijne

    2011-12-01

    The serotonergic system is disturbed in different mood and affective disorders, with especially the serotonin (5-HT) 2A receptor involved in impulsive aggressiveness and anxiety. The aim of the study was to evaluate the involvement of the brain 5-HT 2A receptor in dogs with different behavioural disorders. Three groups of drug naive dogs were studied: 22 dogs showing impulsive aggressive behaviour, 22 showing normal behaviour, and 22 showing anxious behaviour. The serotonin 2A receptor was evaluated with Single Photon Emission Computed Tomography (SPECT) and the serotonin 2A receptor-selective radiopharmaceutical (123)I-R91150. A serotonin 2A receptor binding index (BI), proportional to the cortical receptor density, was calculated. A receiver operating characteristic (ROC) analysis was performed to determine cut-off values at which optimal sensitivity and specificity are achieved and to evaluate the general performance of the BI in reflecting the state of the dog, i.e., impulsive aggressive, normal or anxious. Significantly (Pdogs behaving abnormally, with consistently increased BI in impulsive aggressive dogs and decreased BI in anxious dogs. These results provide clear evidence for a disturbed serotonergic balance in canine impulsive aggression and anxiety disorders. A right frontal cut-off value of ≥1.92 with 86.4% sensitivity and 2.3% (1-specificity) was obtained for the impulsive aggressive dogs. Differentiating the anxious dogs from the rest of the population was possible with a cut-off value of ≤1.73 with 86.4% sensitivity and 18.2% (1-specificity). We conclude that SPECT imaging with the radioligand (123)I-R91150 can be a helpful tool in evaluating the involvement of the serotonin 2A receptor in the complex mechanisms of impulsive aggressive and anxious behaviour. The 5HT-2A binding index of the right frontal cortex appears to be a valid biomarker in differentiating the studied canine behavioural disorders.

  19. Charting a roadmap for heart failure biomarker studies.

    Science.gov (United States)

    Ahmad, Tariq; Fiuzat, Mona; Pencina, Michael J; Geller, Nancy L; Zannad, Faiez; Cleland, John G F; Snider, James V; Blankenberg, Stephan; Adams, Kirkwood F; Redberg, Rita F; Kim, Jae B; Mascette, Alice; Mentz, Robert J; O'Connor, Christopher M; Felker, G Michael; Januzzi, James L

    2014-10-01

    Heart failure is a syndrome with a pathophysiological basis that can be traced to dysfunction in several interconnected molecular pathways. Identification of biomarkers of heart failure that allow measurement of the disease on a molecular level has resulted in enthusiasm for their use in prognostication and selection of appropriate therapies. However, despite considerable amounts of information available on numerous biomarkers, inconsistent research methodologies and lack of clinical correlations have made bench-to-bedside translations rare and left the literature with countless publications of varied quality. There is a need for a systematic and collaborative approach aimed at definitively studying the clinical benefits of novel biomarkers. In this review, on the basis of input from academia, industry, and governmental agencies, we propose a systematized approach based on adherence to specific quality measures for studies looking to augment current prediction model or use biomarkers to tailor therapeutics. We suggest that study quality, rather than results, should determine publication and propose a system for grading biomarker studies. We outline the need for collaboration between clinical investigators and statisticians to introduce more advanced statistical methodologies into the field of biomarkers that would allow for data from a large number of variables to be distilled into clinically actionable information. Lastly, we propose the creation of a heart failure biomarker consortium that would allow for a comprehensive list of biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and hypotheses to be generated for testing in biomarker-guided trials. Such a consortium could collaborate in sharing samples to identify biomarkers, undertake meta-analyses on completed trials, and spearhead clinical trials to test the clinical utility of new biomarkers.

  20. GFAP and S100B are biomarkers of traumatic brain injury : an observational cohort study

    NARCIS (Netherlands)

    Vos, P E; Jacobs, B; Andriessen, T M J C; Lamers, K J B; Borm, G F; Beems, T; Edwards, M; Rosmalen, C F; Vissers, J L M

    2010-01-01

    BACKGROUND: Biomarker levels in blood after traumatic brain injury (TBI) may offer diagnostic and prognostic tools in addition to clinical indices. This study aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations in blood as outcome predictors of TBI using cutoff levels of

  1. Biomarkers intersect with the exposome.

    Science.gov (United States)

    Rappaport, Stephen M

    2012-09-01

    The exposome concept promotes use of omic tools for discovering biomarkers of exposure and biomarkers of disease in studies of diseased and healthy populations. A two-stage scheme is presented for profiling omic features in serum to discover molecular biomarkers and then for applying these biomarkers in follow-up studies. The initial component, referred to as an exposome-wide-association study (EWAS), employs metabolomics and proteomics to interrogate the serum exposome and, ultimately, to identify, validate and differentiate biomarkers of exposure and biomarkers of disease. Follow-up studies employ knowledge-driven designs to explore disease causality, prevention, diagnosis, prognosis and treatment.

  2. Discovery and Validation of Prognostic Biomarker Models to Guide Triage among Adult Dengue Patients at Early Infection

    Science.gov (United States)

    Tolfvenstam, Thomas; Thein, Tun-Linn; Naim, Ahmad Nazri Mohamed; Ling, Ling; Chow, Angelia; Chen, Mark I-Cheng; Ooi, Eng Eong; Leo, Yee Sin; Hibberd, Martin L.

    2016-01-01

    Background Dengue results in a significant public health burden in endemic regions. The World Health Organization (WHO) recommended the use of warning signs (WS) to stratify patients at risk of severe dengue disease in 2009. However, WS is limited in stratifying adult dengue patients at early infection (Day 1–3 post fever), who require close monitoring in hospitals to prevent severe dengue. The aim of this study is to identify and validate prognostic models, built with differentially expressed biomarkers, that enable the early identification of those with early dengue infection that require close clinical monitoring. Methods RNA microarray and protein assays were performed to identify differentially expressed biomarkers of severity among 92 adult dengue patients recruited at early infection from years 2005–2008. This comprised 47 cases who developed WS after first presentation and required hospitalization (WS+Hosp), as well as 45 controls who did not develop WS after first presentation and did not require hospitalization (Non-WS+Non-Hosp). Independent validation was conducted with 80 adult dengue patients recruited from years 2009–2012. Prognostic models were developed based on forward stepwise and backward elimination estimation, using multiple logistic regressions. Prognostic power was estimated by the area under the receiver operating characteristic curve (AUC). Results The WS+Hosp group had significantly higher viral load (Pdengue patients at early infection, with sensitivity and specificity up to 83% and 84%, respectively. These results were tested in the independent validation group, showing sensitivity and specificity up to 96% and 54.6%, respectively. Conclusions At early infection, adult dengue patients who later presented WS and require hospitalization have significantly different pathophysiology compared with patients who consistently presented no WS and / or require no hospitalization. The molecular prognostic models developed and validated here

  3. Statistical design for biospecimen cohort size in proteomics-based biomarker discovery and verification studies.

    Science.gov (United States)

    Skates, Steven J; Gillette, Michael A; LaBaer, Joshua; Carr, Steven A; Anderson, Leigh; Liebler, Daniel C; Ransohoff, David; Rifai, Nader; Kondratovich, Marina; Težak, Živana; Mansfield, Elizabeth; Oberg, Ann L; Wright, Ian; Barnes, Grady; Gail, Mitchell; Mesri, Mehdi; Kinsinger, Christopher R; Rodriguez, Henry; Boja, Emily S

    2013-12-01

    Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor, and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC) with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step toward building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research.

  4. The role of metabolic biomarkers in drug toxicity studies.

    Science.gov (United States)

    Schnackenberg, Laura K; Beger, Richard D

    2008-01-01

    ABSTRACT Metabolic profiling is a technique that can potentially provide more sensitive and specific biomarkers of toxicity than the current clinical measures benefiting preclinical and clinical drug studies. Both nuclear magnetic resonance (NMR) and mass spectrometry (MS) platforms have been used for metabolic profiling studies of drug toxicity. Not only can both techniques provide novel biomarker(s) of toxicity but the combination of both techniques gives a broader range of metabolites evaluated. Changes in metabolic patterns can provide insight into mechanism(s) of toxicity and help to eliminate a potentially toxic new chemical entity earlier in the developmental process. Metabolic profiling offers numerous advantages in toxicological research and screening as sample collection and preparation are relatively simple. Further, sample throughput, reproducibility, and accuracy are high. The area of drug toxicity of therapeutic compounds has already been impacted by metabolic profiling studies and will continue to be impacted as new, more specific biomarker(s) are found. In order for a biomarker or pattern of biomarkers to be accepted, it must be shown that they originate from the target tissue of interest. Metabolic profiling studies are amenable to any biofluid or tissue sample making it possible to link the changes noted in urine for instance as originating from renal injury. Additionally, the ease of sample collection makes it possible to follow a single animal or subject over time in order to determine whether and when the toxicity resolves itself. This review focuses on the advantages of metabolic profiling for drug toxicity studies.

  5. SurvExpress: an online biomarker validation tool and database for cancer gene expression data using survival analysis.

    Directory of Open Access Journals (Sweden)

    Raul Aguirre-Gamboa

    Full Text Available Validation of multi-gene biomarkers for clinical outcomes is one of the most important issues for cancer prognosis. An important source of information for virtual validation is the high number of available cancer datasets. Nevertheless, assessing the prognostic performance of a gene expression signature along datasets is a difficult task for Biologists and Physicians and also time-consuming for Statisticians and Bioinformaticians. Therefore, to facilitate performance comparisons and validations of survival biomarkers for cancer outcomes, we developed SurvExpress, a cancer-wide gene expression database with clinical outcomes and a web-based tool that provides survival analysis and risk assessment of cancer datasets. The main input of SurvExpress is only the biomarker gene list. We generated a cancer database collecting more than 20,000 samples and 130 datasets with censored clinical information covering tumors over 20 tissues. We implemented a web interface to perform biomarker validation and comparisons in this database, where a multivariate survival analysis can be accomplished in about one minute. We show the utility and simplicity of SurvExpress in two biomarker applications for breast and lung cancer. Compared to other tools, SurvExpress is the largest, most versatile, and quickest free tool available. SurvExpress web can be accessed in http://bioinformatica.mty.itesm.mx/SurvExpress (a tutorial is included. The website was implemented in JSP, JavaScript, MySQL, and R.

  6. Six Serum miRNAs Fail to Validate as Myotonic Dystrophy Type 1 Biomarkers

    Science.gov (United States)

    Fernandez-Costa, Juan M.; Llamusi, Beatriz; Bargiela, Ariadna; Zulaica, Miren; Alvarez-Abril, M. Carmen; Perez-Alonso, Manuel; Lopez de Munain, Adolfo

    2016-01-01

    Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disease caused by expansion of a CTG microsatellite in the 3’ untranslated region of the DMPK gene. Despite characteristic muscular, cardiac, and neuropsychological symptoms, CTG trinucleotide repeats are unstable both in the somatic and germinal lines, making the age of onset, clinical presentation, and disease severity very variable. A molecular biomarker to stratify patients and to follow disease progression is, thus, an unmet medical need. Looking for a novel biomarker, and given that specific miRNAs have been found to be misregulated in DM1 heart and muscle tissues, we profiled the expression of 175 known serum miRNAs in DM1 samples. The differences detected between patients and controls were less than 2.6 fold for all of them and a selection of six candidate miRNAs, miR-103, miR-107, miR-21, miR-29a, miR-30c, and miR-652 all failed to show consistent differences in serum expression in subsequent validation experiments. PMID:26919350

  7. Six Serum miRNAs Fail to Validate as Myotonic Dystrophy Type 1 Biomarkers.

    Directory of Open Access Journals (Sweden)

    Juan M Fernandez-Costa

    Full Text Available Myotonic dystrophy type 1 (DM1 is an autosomal dominant genetic disease caused by expansion of a CTG microsatellite in the 3' untranslated region of the DMPK gene. Despite characteristic muscular, cardiac, and neuropsychological symptoms, CTG trinucleotide repeats are unstable both in the somatic and germinal lines, making the age of onset, clinical presentation, and disease severity very variable. A molecular biomarker to stratify patients and to follow disease progression is, thus, an unmet medical need. Looking for a novel biomarker, and given that specific miRNAs have been found to be misregulated in DM1 heart and muscle tissues, we profiled the expression of 175 known serum miRNAs in DM1 samples. The differences detected between patients and controls were less than 2.6 fold for all of them and a selection of six candidate miRNAs, miR-103, miR-107, miR-21, miR-29a, miR-30c, and miR-652 all failed to show consistent differences in serum expression in subsequent validation experiments.

  8. Six Serum miRNAs Fail to Validate as Myotonic Dystrophy Type 1 Biomarkers.

    Science.gov (United States)

    Fernandez-Costa, Juan M; Llamusi, Beatriz; Bargiela, Ariadna; Zulaica, Miren; Alvarez-Abril, M Carmen; Perez-Alonso, Manuel; Lopez de Munain, Adolfo; Lopez-Castel, Arturo; Artero, Ruben

    2016-01-01

    Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disease caused by expansion of a CTG microsatellite in the 3' untranslated region of the DMPK gene. Despite characteristic muscular, cardiac, and neuropsychological symptoms, CTG trinucleotide repeats are unstable both in the somatic and germinal lines, making the age of onset, clinical presentation, and disease severity very variable. A molecular biomarker to stratify patients and to follow disease progression is, thus, an unmet medical need. Looking for a novel biomarker, and given that specific miRNAs have been found to be misregulated in DM1 heart and muscle tissues, we profiled the expression of 175 known serum miRNAs in DM1 samples. The differences detected between patients and controls were less than 2.6 fold for all of them and a selection of six candidate miRNAs, miR-103, miR-107, miR-21, miR-29a, miR-30c, and miR-652 all failed to show consistent differences in serum expression in subsequent validation experiments.

  9. Banking of biological fluids for studies of disease-associated protein biomarkers

    DEFF Research Database (Denmark)

    Rasmussen, Anne-Sofie Schrohl; Würtz, Sidse Ørnbjerg; Kohn, Elise

    2008-01-01

    and prognostic classification to prediction of response to therapy. Clinically validated biomarkers may provide information to be used for diagnosis, screening, evaluation of risk/predisposition, assessment of prognosis, monitoring (recurrence of disease), and prediction of response to treatment...... of the samples, and handling and storage of samples. Critical points in each step important for high quality biomarker studies are described in this review. Failure to develop and adhere to robust standardized protocols may have significant consequences as the quality of the material stored in the biobank...

  10. Parkinson's disease plasma biomarkers: an automated literature analysis followed by experimental validation.

    Science.gov (United States)

    Alberio, Tiziana; Bucci, Enrico M; Natale, Massimo; Bonino, Dario; Di Giovanni, Marco; Bottacchi, Edo; Fasano, Mauro

    2013-09-02

    Diagnosis of Parkinson's disease (PD) is currently assessed by the clinical evaluation of extrapyramidal signs. The identification of specific biomarkers would be advisable, however most studies stop at the discovery phase, with no biomarkers reaching clinical exploitation. To this purpose, we developed an automated literature analysis procedure to retrieve all the background knowledge available in public databases. The bioinformatic platform allowed us to analyze more than 51,000 scientific papers dealing with PD, containing information on 4121 proteins. Out of these, we could track back 35 PD-related proteins as present in at least two published 2-DE maps of human plasma. Then, 9 different proteins (haptoglobin, transthyretin, apolipoprotein A-1, serum amyloid P component, apolipoprotein E, complement factor H, fibrinogen γ, thrombin, complement C3) split into 32 spots were identified as a potential diagnostic pattern. Eventually, we compared the collected literature data to experimental gels from 90 subjects (45 PD patients, 45 non-neurodegenerative control subjects) to experimentally verify their potential as plasma biomarkers of PD.

  11. Discovery and validation of plasma biomarkers for major depressive disorder classification based on liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Liu, Xinyu; Zheng, Peng; Zhao, Xinjie; Zhang, Yuqing; Hu, Chunxiu; Li, Jia; Zhao, Jieyu; Zhou, Jingjing; Xie, Peng; Xu, Guowang

    2015-05-01

    Major depressive disorder (MDD) is a debilitating mental disease with a pronounced impact on the quality of life of many people; however, it is still difficult to diagnose MDD accurately. In this study, a nontargeted metabolomics approach based on ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to find the differential metabolites in plasma samples from patients with MDD and healthy controls. Furthermore, a validation analysis focusing on the differential metabolites was performed in another batch of samples using a targeted approach based on the dynamic multiple reactions monitoring method. Levels of acyl carnitines, ether lipids, and tryptophan pronouncedly decreased, whereas LPCs, LPEs, and PEs markedly increased in MDD subjects as compared with the healthy controls. Disturbed pathways, mainly located in acyl carnitine metabolism, lipid metabolism, and tryptophan metabolism, were clearly brought to light in MDD subjects. The binary logistic regression result showed that carnitine C10:1, PE-O 36:5, LPE 18:1 sn-2, and tryptophan can be used as a combinational biomarker to distinguish not only moderate but also severe MDD from healthy control with good sensitivity and specificity. Our findings, on one hand, provide critical insight into the pathological mechanism of MDD and, on the other hand, supply a combinational biomarker to aid the diagnosis of MDD in clinical usage.

  12. Prospective transcriptomic pathway analysis of human lymphatic vascular insufficiency: identification and validation of a circulating biomarker panel.

    Directory of Open Access Journals (Sweden)

    Shin Lin

    Full Text Available BACKGROUND: In our previous transcriptional profiling of a murine model, we have identified a remarkably small number of specific pathways with altered expression in lymphedema. In this investigation, we utilized microarray-based transcriptomics of human skin for an unbiased a priori prospective candidate identification, with subsequent validation of these candidates through direct serum assay. The resulting multi-analyte biomarker panel sensitively should sensitively discriminate human lymphedema subjects from normal individuals. METHODS AND FINDINGS: We enrolled 63 lymphedema subjects and 27 normals in our attempt to discover protein analytes that can distinguish diseased individuals from controls. To minimize technical and biologically irrelevant variation, we first identified potential candidates by performing transcriptional microarray analysis on paired diseased and normal skin specimens sampled from the same individuals. We focused our attention on genes with corresponding protein products that are secreted and took these candidates forward to a protein multiplex assay applied to diseased and normal subjects. We developed a logistic regression-based model on an eventual group of six proteins and validated our system on a separate cohort of study subjects. The area under the receiver operating characteristic curve was calculated to be 0.87 (95% CI : 0.75 to 0.97. CONCLUSIONS: We have developed an accurate bioassay utilizing proteins representing four central pathogenetic modalities of the disease: lymphangiogenesis, inflammation, fibrosis, and lipid metabolism, suggesting that these proteins are directly related to the pathogenesis of the tissue pathology in lymphatic vascular insufficiency. Further studies are warranted to determine whether this newly-identified biomarker panel will possess utility as an instrument for in vitro diagnosis of early and latent disease; the ultimate applicability to risk stratification, quantitation of

  13. Skin carotenoids as biomarker for vegetable and fruit intake: Validation of the reflection-spectroscopy based “Veggie Meter”

    Science.gov (United States)

    Skin is a relatively stable storage medium for carotenoids; non-invasive optical measurements of carotenoids in this tissue via Resonance Raman spectroscopy (RRS) serve as a non-invasive biomarker for fruit and vegetable (F/V) intake. The RRS method has been validated with HPLC-based measurements of...

  14. A short food frequency questionnaire to assess intake of seafood and n-3 supplements: validation with biomarkers

    Directory of Open Access Journals (Sweden)

    Dahl Lisbeth

    2011-11-01

    Full Text Available Abstract Background Seafood intake is associated with beneficial effects for human health. Seafood provides a number of nutrients beyond the traditionally known long chain marine n-3 fatty acids EPA, DPA and DHA, such as protein, vitamin D, iodine, selenium and vitamin B12. Valid assessment of dietary seafood and n-3 supplement intakes are becoming increasingly crucial when giving recommendations to populations as seafood consumption is regarded as an important part of a healthy and balanced diet. Methods The aim was to validate a short FFQ developed for assessment of dietary intake of seafood and n-3 supplements using the biomarkers marine n-3 fatty acids in erythrocytes and 25(OHD in serum. Results Fifty-three healthy Norwegians aged 30-64 years with a mean BMI of 25 kg/m2 were compliant with the study protocol. 70% reported eating seafood for dinner one to two times per week, and 45% reported to eat seafood as spread, in salads or as snack meal three to five times or more per week. The FFQ correlated significantly with both the levels of marine n-3 fatty acids (r = 0.73, p Conclusion The present short FFQ predicted strongly the levels of marine n-3 fatty acids in erythrocytes, and predicted fairly good the level of serum 25(OHD and may therefore be a valid method for assessment of seafood and n-3 supplements intake among adults.

  15. Will the future lie in multitude? A critical appraisal of biomarker panel studies on prediction of diabetic kidney disease progression.

    Science.gov (United States)

    Schutte, Elise; Gansevoort, Ron T; Benner, Jacqueline; Lutgers, Helen L; Lambers Heerspink, Hiddo J

    2015-08-01

    Diabetic kidney disease is diagnosed and staged by albuminuria and estimated glomerular filtration rate. Although albuminuria has strong predictive power for renal function decline, there is still variability in the rate of renal disease progression across individuals that are not fully captured by the level of albuminuria. Therefore, research focuses on discovering and validating additional biomarkers that improve risk stratification for future renal function decline and end-stage renal disease in patients with diabetes, on top of established biomarkers. Most studies address the value of single biomarkers to predict progressive renal disease and aim to understand the mechanisms that underlie accelerated renal function decline. Since diabetic kidney disease is a disease encompassing several pathophysiological processes, a combination of biomarkers may be more likely to improve risk prediction than a single biomarker. In this review, we provide an overview of studies on the use of multiple biomarkers and biomarker panels, appraise their study design, discuss methodological pitfalls and make recommendations for future biomarker panel studies.

  16. Practical Guidance for Implementing Predictive Biomarkers into Early Phase Clinical Studies

    Directory of Open Access Journals (Sweden)

    Matthew J. Marton

    2013-01-01

    Full Text Available The recent U.S. Food and Drug Administration (FDA coapprovals of several therapeutic compounds and their companion diagnostic devices (FDA News Release, 2011, 2013 to identify patients who would benefit from treatment have led to considerable interest in incorporating predictive biomarkers in clinical studies. Yet, the translation of predictive biomarkers poses unique technical, logistic, and regulatory challenges that need to be addressed by a multidisciplinary team including discovery scientists, clinicians, biomarker experts, regulatory personnel, and assay developers. These issues can be placed into four broad categories: sample collection, assay validation, sample analysis, and regulatory requirements. In this paper, we provide a primer for drug development teams who are eager to implement a predictive patient segmentation marker into an early clinical trial in a way that facilitates subsequent development of a companion diagnostic. Using examples of nucleic acid-based assays, we briefly review common issues encountered when translating a biomarker to the clinic but focus primarily on key practical issues that should be considered by clinical teams when planning to use a biomarker to balance arms of a study or to determine eligibility for a clinical study.

  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. Validation of methods to assess potential biomarkers in pediatric patients with esophageal eosinophilia

    Institute of Scientific and Technical Information of China (English)

    Jennifer; M; Colombo; Nancy; A; Neilan; Jennifer; Verrill; Schurman; Craig; A; Friesen

    2013-01-01

    the best in predicting classification of HE vs LE,with mean MBP demonstrating 100% sensitivity and95% specificity at the optimal cut point.CONCLUSION:This study provides methodology and proof-of-concept for future evaluation of these biomarkers for differentiating esophageal eosinophilic diseases such as reflux esophagitis and eosinophilic esophagitis.

  19. Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Sudhanshu Shukla

    2016-08-01

    Full Text Available Rapid advances in the discovery of long noncoding RNAs (lncRNAs have identified lineage- and cancer-specific biomarkers that may be relevant in the clinical management of prostate cancer (PCa. Here we assembled and analyzed a large RNA-seq dataset, from 585 patient samples, including benign prostate tissue and both localized and metastatic PCa to discover and validate differentially expressed genes associated with disease aggressiveness. We performed Sample Set Enrichment Analysis (SSEA and identified genes associated with low versus high Gleason score in the RNA-seq database. Comparing Gleason 6 versus 9+ PCa samples, we identified 99 differentially expressed genes with variable association to Gleason grade as well as robust expression in prostate cancer. The top-ranked novel lncRNA PCAT14, exhibits both cancer and lineage specificity. On multivariate analysis, low PCAT14 expression independently predicts for BPFS (P = .00126, PSS (P = .0385, and MFS (P = .000609, with trends for OS as well (P = .056. An RNA in-situ hybridization (ISH assay for PCAT14 distinguished benign vs malignant cases, as well as high vs low Gleason disease. PCAT14 is transcriptionally regulated by AR, and endogenous PCAT14 overexpression suppresses cell invasion. Thus, Using RNA-sequencing data we identify PCAT14, a novel prostate cancer and lineage-specific lncRNA. PCAT14 is highly expressed in low grade disease and loss of PCAT14 predicts for disease aggressiveness and recurrence.

  20. Parkinsons Disease-related Circulating microRNA Biomarkers——a Validation Study

    Directory of Open Access Journals (Sweden)

    David Petillo

    2015-02-01

    Full Text Available Parkinson's disease (PD is the second most common neurodegenerative disease. One of the major challenges in studying this progressive neurological disorder is to identify and develop biomarkers for early detection. Recently, several blood-based microRNA (miRNA biomarkers for PD have been reported. However, follow-up studies with new, independent cohorts have been rare. Previously, we identified a panel of four circulating miRNA biomarkers for PD (miR-1826, miR-450b-3p, miR-505, and miR-626 with biomarker performance of 91% sensitivity and 100% specificity. However, the expression of miR-450b-3p could not be detected in a new, independent validation set. In our current study, we improved the detection power by including a non-biased pre-amplification step in quantitative real-time PCR (qRT-PCR and reevaluated the biomarker performance. We found the panel of four PD-related miRNAs achieved the predictive power of 83% sensitivity and 75% specificity in our validation set. This is the first biomarker validation study of PD which showed reproducibility and robustness of plasma-based circulating miRNAs as molecular biomarkers and qRT-PCR as potential diagnostic assay.

  1. Biomarker case-detection and prediction with potential for functional psychosis screening: development and validation of a model related to biochemistry, sensory neural timing and end organ performance.

    Directory of Open Access Journals (Sweden)

    Stephanie eFryar-Williams

    2016-04-01

    Full Text Available The Mental Health Biomarker Project aimed to discover case-predictive biomarkers for functional psychosis. In a retrospective, cross-sectional study, candidate marker results from 67, highly-characterized symptomatic participants were compared with results from 67 gender and age matched controls. Urine samples were analysed for catecholamines, their metabolites and hydroxylpyrolline-2-one, an oxidative stress marker. Blood samples were analyzed for vitamin and trace element cofactors of enzymes in the catecholamine synthesis and metabolism pathways. Cognitive, auditory and visual processing measures were assessed using a simple 45 minute, office-based procedure. Receiver Operating Curve (ROC and Odds Ratio analysis discovered biomarkers for deficits in folate, vitamin D and B6 and elevations in free copper to zinc ratio, catecholamines and the oxidative stress marker. Deficits were discovered in peripheral visual and auditory end-organ function, intra-cerebral auditory and visual processing speed and dichotic-listening performance. 15 ROC biomarker variables were divided into 5 functional domains. Through a repeated ROC process, individual ROC variables, followed by domains and finally the overall 15 set model, were dichotomously scored and tallied for abnormal results upon which it was found that ≥ 3 out of 5 abnormal domains achieved an AUC of 0.952 with a sensitivity of 84 per cent and a specificity of 90 percent. Six additional middle ear biomarkers in a 21 biomarker set increased sensitivity to 94% percent. Fivefold cross-validation yielded a mean sensitivity of 85% for the 15 biomarker set. Non-parametric regression analysis confirmed that ≥ 3 out of 5 abnormally scored domains predicted > 50% risk of case-ness whilst 4 abnormally-scored domains predicted 88% risk of case-ness and 100% diagnostic certainty was reached when all 5 domains were abnormally scored. These findings require validation in prospective cohorts and other mental

  2. CTF Void Drift Validation Study

    Energy Technology Data Exchange (ETDEWEB)

    Salko, Robert K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gosdin, Chris [Pennsylvania State Univ., University Park, PA (United States); Avramova, Maria N. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gergar, Marcus [Pennsylvania State Univ., University Park, PA (United States)

    2015-10-26

    This milestone report is a summary of work performed in support of expansion of the validation and verification (V&V) matrix for the thermal-hydraulic subchannel code, CTF. The focus of this study is on validating the void drift modeling capabilities of CTF and verifying the supporting models that impact the void drift phenomenon. CTF uses a simple turbulent-diffusion approximation to model lateral cross-flow due to turbulent mixing and void drift. The void drift component of the model is based on the Lahey and Moody model. The models are a function of two-phase mass, momentum, and energy distribution in the system; therefore, it is necessary to correctly model the ow distribution in rod bundle geometry as a first step to correctly calculating the void distribution due to void drift.

  3. Statistical considerations of optimal study design for human plasma proteomics and biomarker discovery.

    Science.gov (United States)

    Zhou, Cong; Simpson, Kathryn L; Lancashire, Lee J; Walker, Michael J; Dawson, Martin J; Unwin, Richard D; Rembielak, Agata; Price, Patricia; West, Catharine; Dive, Caroline; Whetton, Anthony D

    2012-04-01

    A mass spectrometry-based plasma biomarker discovery workflow was developed to facilitate biomarker discovery. Plasma from either healthy volunteers or patients with pancreatic cancer was 8-plex iTRAQ labeled, fractionated by 2-dimensional reversed phase chromatography and subjected to MALDI ToF/ToF mass spectrometry. Data were processed using a q-value based statistical approach to maximize protein quantification and identification. Technical (between duplicate samples) and biological variance (between and within individuals) were calculated and power analysis was thereby enabled. An a priori power analysis was carried out using samples from healthy volunteers to define sample sizes required for robust biomarker identification. The result was subsequently validated with a post hoc power analysis using a real clinical setting involving pancreatic cancer patients. This demonstrated that six samples per group (e.g., pre- vs post-treatment) may provide sufficient statistical power for most proteins with changes>2 fold. A reference standard allowed direct comparison of protein expression changes between multiple experiments. Analysis of patient plasma prior to treatment identified 29 proteins with significant changes within individual patient. Changes in Peroxiredoxin II levels were confirmed by Western blot. This q-value based statistical approach in combination with reference standard samples can be applied with confidence in the design and execution of clinical studies for predictive, prognostic, and/or pharmacodynamic biomarker discovery. The power analysis provides information required prior to study initiation.

  4. Identification and Validation of Protein Biomarkers of Response to Neoadjuvant Platinum Chemotherapy in Muscle Invasive Urothelial Carcinoma.

    Directory of Open Access Journals (Sweden)

    Alexander S Baras

    of both these protein biomarkers detected by IHC in biopsy specimens along with the relevant clinical parameters resulted in a prediction model able to significantly stratify the likelihood of NAC resistance in our cohort (n = 37 into two well separated halves: low-26% n = 19 and high-89% n = 18, Fisher's exact p = 0.0002.We illustrate the feasibility of translating a gene expression signature of NAC response from a discovery cohort into immunohistochemical markers readily applicable to MIBC biopsy specimens in our independent cohort. The results from this study are being characterized in additional validation cohorts. Additionally, we anticipate that emerging somatic mutations in MIBC will also be important for NAC response prediction. The relationship of the findings in this study to the current understanding of variant histologic subtypes of MIBC along with the evolving molecular subtypes of MIBC as it relates to NAC response remains to be fully characterized.

  5. 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

    ) by using the method of triads. The intakes of fruit, juice, vegetables and tea reported in the FFQ were reflected by the flavonoid biomarker both in overnight and 24 h urine samples. Validity coefficients for the flavonoid biomarker in overnight urine ranged from 0.39 to 0.49, while the corresponding...... in overnight urine samples may be used as a more feasible biomarker than 24 h urine for the assessment and validation of fruit, juice, vegetable and tea intakes in epidemiological studies. Copyright © The Authors 2012....... 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...

  6. Development and validation of a skin fibroblast biomarker profile for schizophrenic patients

    Directory of Open Access Journals (Sweden)

    Marianthi Logotheti

    2016-12-01

    Full Text Available Gene expression profiles of non-neural tissues through microarray technology could be used in schizophrenia studies, adding more information to the results from similar studies on postmortem brain tissue. The ultimate goal of such studies is to develop accessible biomarkers. Supervised machine learning methodologies were used, in order to examine if the gene expression from skin fibroblast cells could be exploited for the classification of schizophrenic subjects. A dataset of skin fibroblasts gene expression of schizophrenia patients was obtained from Gene Expression Omnibus database. After applying statistical criteria, we concluded to genes that present a differential expression between the schizophrenic patients and the healthy controls. Based on those genes, functional profiling was performed with the BioInfoMiner web tool. After the statistical analysis, 63 genes were identified as differentially expressed. The functional profiling revealed interesting terms and pathways, such as mitogen activated protein kinase and cyclic adenosine monophosphate signaling pathways, as well as immune-related mechanisms. A subset of 16 differentially expressed genes from fibroblast gene expression profiling that occurred after Support Vector Machines Recursive Feature Elimination could efficiently separate schizophrenic from healthy controls subjects. These findings suggest that through the analysis of fibroblast based gene expression signature and with the application of machine learning methodologies we might conclude to a diagnostic classification model in schizophrenia.

  7. Genetic and biomarker studies of human longevity

    NARCIS (Netherlands)

    Deelen, Joris

    2014-01-01

    The aim of this thesis was to identify novel lifespan regulating loci that influence human longevity and population mortality. To this end, we performed two genome-wide association studies, one of long-lived individuals from the family-based Leiden Longevity Study (LLS) and an extended one of long-l

  8. 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

    2016-06-01

    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.

  9. Systematic review of clinical studies examining biomarkers of brain injury in athletes after sports-related concussion.

    Science.gov (United States)

    Papa, Linda; Ramia, Michelle M; Edwards, Damyan; Johnson, Brian D; Slobounov, Semyon M

    2015-05-15

    The aim of this study was to systematically review clinical studies examining biofluid biomarkers of brain injury for concussion in athletes. Data sources included PubMed, MEDLINE, and the Cochrane Database from 1966 to October 2013. Studies were included if they recruited athletes participating in organized sports who experienced concussion or head injury during a sports-related activity and had brain injury biomarkers measured. Acceptable research designs included experimental, observational, and case-control studies. Review articles, opinion papers, and editorials were excluded. After title and abstract screening of potential articles, full texts were independently reviewed to identify articles that met inclusion criteria. A composite evidentiary table was then constructed and documented the study title, design, population, methods, sample size, outcome measures, and results. The search identified 52 publications, of which 13 were selected and critically reviewed. All of the included studies were prospective and were published either in or after the year 2000. Sports included boxing (six studies), soccer (five studies), running/jogging (two studies), hockey (one study), basketball (one study), cycling (one study), and swimming (one study). The majority of studies (92%) had fewer than 100 patients. Three studies (23%) evaluated biomarkers in cerebrospinal fluid (CSF), one in both serum and CSF, and 10 (77%) in serum exclusively. There were 11 different biomarkers assessed, including S100β, glial fibrillary acidic protein, neuron-specific enolase, tau, neurofilament light protein, amyloid beta, brain-derived neurotrophic factor, creatine kinase and heart-type fatty acid binding protein, prolactin, cortisol, and albumin. A handful of biomarkers showed a correlation with number of hits to the head (soccer), acceleration/deceleration forces (jumps, collisions, and falls), postconcussive symptoms, trauma to the body versus the head, and dynamics of different sports

  10. Emerging treatments in management of prostate cancer: biomarker validation and endpoints for immunotherapy clinical trial design

    Directory of Open Access Journals (Sweden)

    Slovin SF

    2013-12-01

    Full Text Available Susan F SlovinGenitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: The rapidly emerging field of immunotherapy and the development of novel immunologic agents that have been approved in melanoma and successfully studied in lung cancer, kidney cancer, and prostate cancer have mandated that there be uniformity in clinical trial analysis beyond conventional survival endpoints and imaging. This includes some measure of determining whether the immunologic target is hit and how the treatment has impacted on the immune system in toto. While melanoma is leading the field towards these ends, there is some doubt that not all of the recent successes with immune therapies, for example, checkpoint inhibitors, will be effective for every cancer, and that the toxicities may also be different depending on the malignancy. This review serves to elucidate the current issues facing clinical investigators who perform immunologic trials targeted at patients with prostate cancer and discusses the challenges in assessing the right immunologic endpoints to demonstrate biologic/immunologic targeting leading to clinical benefit.Keywords: sipuleucel-T, prostate-specific antigen, prostate cancer, biomarkers, monoclonal antibodies, vaccines, cellular therapy

  11. On consensus biomarker selection

    Directory of Open Access Journals (Sweden)

    Gambin Anna

    2007-05-01

    Full Text Available Abstract Background Recent development of mass spectrometry technology enabled the analysis of complex peptide mixtures. A lot of effort is currently devoted to the identification of biomarkers in human body fluids like serum or plasma, based on which new diagnostic tests for different diseases could be constructed. Various biomarker selection procedures have been exploited in recent studies. It has been noted that they often lead to different biomarker lists and as a consequence, the patient classification may also vary. Results Here we propose a new approach to the biomarker selection problem: to apply several competing feature ranking procedures and compute a consensus list of features based on their outcomes. We validate our methods on two proteomic datasets for the diagnosis of ovarian and prostate cancer. Conclusion The proposed methodology can improve the classification results and at the same time provide a unified biomarker list for further biological examinations and interpretation.

  12. Validation of methylation biomarkers that distinguish normal colon mucosa of cancer patients from normal colon mucosa of patients without cancer.

    Science.gov (United States)

    Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen

    2014-07-01

    We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of patients with colon cancer and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 patients with cancer and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of ten of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r = 0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy.

  13. Biomarker patterns in present-day vegetation: consistency and variation - A study on plaggen soils

    Science.gov (United States)

    Kirkels, Frédérique; Jansen, Boris; Kalbitz, Karsten

    2013-04-01

    tissues, which hindered full statistical analysis. On species level we also recognized outliers and spreading. Systematic variation was indicated among tree species according to spatial conditions and by ontogeny. Yet, observed effects were ambiguous for other variation sources. This study highlights clear opportunities for application of biomarker patterns for source identification and elucidation of stabilization processes in (plaggen) soils. At the same time, application is challenged by systematic variation. Further research is key to quantify controls, magnitude and potential correction factors for such systematic variation. This would validate the use of n-alkane and n-alcohol patterns across broad spatial and temporal scales or identify boundaries wherein their consistency is ensured. Likely, these challenges apply to vegetation in a broad perspective, transcending plaggen vegetation, as assessment and application of present-day vegetation patterns is emerging.

  14. Validation of proposed prostate cancer biomarkers with gene expression data: a long road to travel.

    Science.gov (United States)

    Amaro, Adriana; Esposito, Alessia Isabella; Gallina, Anna; Nees, Matthias; Angelini, Giovanna; Albini, Adriana; Pfeffer, Ulrich

    2014-09-01

    Biomarkers are important for early detection of cancer, prognosis, response prediction, and detection of residual or relapsing disease. Special attention has been given to diagnostic markers for prostate cancer since it is thought that early detection and surgery might reduce prostate cancer-specific mortality. The use of prostate-specific antigen, PSA (KLK3), has been debated on the base of cohort studies that show that its use in preventive screenings only marginally influences mortality from prostate cancer. Many groups have identified alternative or additional markers, among which PCA3, in order to detect early prostate cancer through screening, to distinguish potentially lethal from indolent prostate cancers, and to guide the treatment decision. The large number of markers proposed has led us to the present study in which we analyze these indicators for their diagnostic and prognostic potential using publicly available genomic data. We identified 380 markers from literature analysis on 20,000 articles on prostate cancer markers. The most interesting ones appeared to be claudin 3 (CLDN3) and alpha-methysacyl-CoA racemase highly expressed in prostate cancer and filamin C (FLNC) and keratin 5 with highest expression in normal prostate tissue. None of the markers proposed can compete with PSA for tissue specificity. The indicators proposed generally show a great variability of expression in normal and tumor tissue or are expressed at similar levels in other tissues. Those proposed as prognostic markers distinguish cases with marginally different risk of progression and appear to have a clinically limited use. We used data sets sampling 152 prostate tissues, data sets with 281 prostate cancers analyzed by microarray analysis and a study of integrated genomics on 218 cases to develop a multigene score. A multivariate model that combines several indicators increases the discrimination power but does not add impressively to the information obtained from Gleason

  15. Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criteria for Alzheimer’s disease

    Science.gov (United States)

    Jack, Clifford R; Barkhof, Frederik; Bernstein, Matt A; Cantillon, Marc; Cole, Patricia E; DeCarli, Charles; Dubois, Bruno; Duchesne, Simon; Fox, Nick C; Frisoni, Giovanni B; Hampel, Harald; Hill, Derek LG; Johnson, Keith; Mangin, Jean-François; Scheltens, Philip; Schwarz, Adam J; Sperling, Reisa; Suhy, Joyce; Thompson, Paul M; Weiner, Michael; Foster, Norman L

    2012-01-01

    Background The promise of Alzheimer’s disease (AD) biomarkers has led to their incorporation in new diagnostic criteria and in therapeutic trials; however, significant barriers exist to widespread use. Chief among these is the lack of internationally accepted standards for quantitative metrics. Hippocampal volumetry is the most widely studied quantitative magnetic resonance imaging (MRI) measure in AD and thus represents the most rational target for an initial effort at standardization. Methods and Results The authors of this position paper propose a path toward this goal. The steps include: 1) Establish and empower an oversight board to manage and assess the effort, 2) Adopt the standardized definition of anatomic hippocampal boundaries on MRI arising from the EADC-ADNI hippocampal harmonization effort as a Reference Standard, 3) Establish a scientifically appropriate, publicly available Reference Standard Dataset based on manual delineation of the hippocampus in an appropriate sample of subjects (ADNI), and 4) Define minimum technical and prognostic performance metrics for validation of new measurement techniques using the Reference Standard Dataset as a benchmark. Conclusions Although manual delineation of the hippocampus is the best available reference standard, practical application of hippocampal volumetry will require automated methods. Our intent is to establish a mechanism for credentialing automated software applications to achieve internationally recognized accuracy and prognostic performance standards that lead to the systematic evaluation and then widespread acceptance and use of hippocampal volumetry. The standardization and assay validation process outlined for hippocampal volumetry is envisioned as a template that could be applied to other imaging biomarkers. PMID:21784356

  16. Utilization of never-medicated bipolar disorder patients towards development and validation of a peripheral biomarker profile.

    Directory of Open Access Journals (Sweden)

    Catherine L Clelland

    Full Text Available There are currently no biological tests that differentiate patients with bipolar disorder (BPD from healthy controls. While there is evidence that peripheral gene expression differences between patients and controls can be utilized as biomarkers for psychiatric illness, it is unclear whether current use or residual effects of antipsychotic and mood stabilizer medication drives much of the differential transcription. We therefore tested whether expression changes in first-episode, never-medicated BPD patients, can contribute to a biological classifier that is less influenced by medication and could potentially form a practicable biomarker assay for BPD. We employed microarray technology to measure global leukocyte gene expression in first-episode (n=3 and currently medicated BPD patients (n=26, and matched healthy controls (n=25. Following an initial feature selection of the microarray data, we developed a cross-validated 10-gene model that was able to correctly predict the diagnostic group of the training sample (26 medicated patients and 12 controls, with 89% sensitivity and 75% specificity (p<0.001. The 10-gene predictor was further explored via testing on an independent cohort consisting of three pairs of monozygotic twins discordant for BPD, plus the original enrichment sample cohort (the three never-medicated BPD patients and 13 matched control subjects, and a sample of experimental replicates (n=34. 83% of the independent test sample was correctly predicted, with a sensitivity of 67% and specificity of 100% (although this result did not reach statistical significance. Additionally, 88% of sample diagnostic classes were classified correctly for both the enrichment (p=0.015 and the replicate samples (p<0.001. We have developed a peripheral gene expression biomarker profile, that can classify healthy controls from patients with BPD receiving antipsychotic or mood stabilizing medication, which has both high sensitivity and specificity

  17. Texture analysis of liver fibrosis microscopic images: a study on the effect of biomarkers

    Institute of Scientific and Technical Information of China (English)

    Amr Amin; Doaa Mahmoud-Ghoneim

    2011-01-01

    Chronic hepatic injury results in liver fibrosis with eventual progression to irreversible cirrhosis. Liver fibrogenesis involves the activation of the quiescent hepatic stellate cell into an activated myofibroblast that is characterized by α-smooth muscle actin (α-SMA) expression and the production of collagens (types Ⅰ and Ⅲ). In the present study,rats were randomly divided into three groups: (i) control group, where rats were only treated with a vehicle; (ii) fibrosis group, where rats were treated with carbon tetrachloride (CCl4) to induce liver fibrosis; and (iii) silymarin group,where rats were protected with silymarin during CCl4 treatment. Rats were sacrificed and sections of liver tissue were counterstained with hematoxylin and eosin and Masson's trichrome. Other sections were immunostained using collagens and α-SMA primary antibodies. Fibrosis was confirmed using serum marker measurements. Microscopic images of the stained sections were acquired and digitized.The Biomarker Index of Fibrosis (BIF) was calculated from the images by quantifying the percentage of stained fibers.Statistical methods of texture analysis (TA), namely cooccurrence and run-length matrices, were applied on the digital images followed by classification using agglomerative hierarchical clustering and linear discriminant analysis with cross validation. TA applied on different biomarkers was successful in discriminating between the groups,showing 100% sensitivity and specificity for classification between the control and fibrosis groups using any biomarker. Some classification attempts showed dependence on the biomarker used, especially for classification between the silymarin and fibrosis groups, which showed optimal results using Masson's trichrome. TA results were consistent with both BIF and serum marker measurements.

  18. Blood diagnostic biomarkers for major depressive disorder using multiplex DNA methylation profiles: discovery and validation.

    Science.gov (United States)

    Numata, Shusuke; Ishii, Kazuo; Tajima, Atsushi; Iga, Jun-ichi; Kinoshita, Makoto; Watanabe, Shinya; Umehara, Hidehiro; Fuchikami, Manabu; Okada, Satoshi; Boku, Shuken; Hishimoto, Akitoyo; Shimodera, Shinji; Imoto, Issei; Morinobu, Shigeru; Ohmori, Tetsuro

    2015-01-01

    Aberrant DNA methylation in the blood of patients with major depressive disorder (MDD) has been reported in several previous studies. However, no comprehensive studies using medication-free subjects with MDD have been conducted. Furthermore, the majority of these previous studies has been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions. The main aim of the present study is to identify DNA methylation markers that distinguish patients with MDD from non-psychiatric controls. Genome-wide DNA methylation profiling of peripheral leukocytes was conducted in two set of samples, a discovery set (20 medication-free patients with MDD and 19 controls) and a replication set (12 medication-free patients with MDD and 12 controls), using Infinium HumanMethylation450 BeadChips. Significant diagnostic differences in DNA methylation were observed at 363 CpG sites in the discovery set. All of these loci demonstrated lower DNA methylation in patients with MDD than in the controls, and most of them (85.7%) were located in the CGIs in the gene promoter regions. We were able to distinguish patients with MDD from the control subjects with high accuracy in the discriminant analysis using the top DNA methylation markers. We also validated these selected DNA methylation markers in the replication set. Our results indicate that multiplex DNA methylation markers may be useful for distinguishing patients with MDD from non-psychiatric controls.

  19. Validation studies in nursing: integrative review

    Directory of Open Access Journals (Sweden)

    Maria Andréia silva Ribeiro

    2013-05-01

    Full Text Available The aim of this study was to analyze the methods used for validation studies in nursing research considering the clinical investigation as phenomenon. We carried out literature at BIREME, CINAHL, PUBMED which contain the terms 'validation studies', 'nursing' and 'clinical' and 21 articles were included in the review. The majority of the studies were conducted in 2008; in North America (USA and European Community (62% in the area of adult health. Most of the phenomena investigated were related to nursing care involving physical and emotional aspects. The content validity has been cited in 71.4% of the articles, criterion validity in 28.5% and construct validity in 23.8%. The reliability by means of Cronbach's alpha was used in the majority of the studies. It was found a knowledge gap concerning the validation estudies in the area of public health, child health and the social phenomena related to nursing care.

  20. Smoking reduction and biomarkers in two longitudinal studies

    DEFF Research Database (Denmark)

    Godtfredsen, Nina; Prescott, Eva; Vestbo, Jørgen

    2006-01-01

    /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......-completion questionnaire. Measurements of biomarkers of smoke intake were taken at the second time-point in the two studies: expired-air carbon monoxide (CO) in the CCHS and serum cotinine in the CMS. Biomarker levels in medium (15-29 g tobacco/day) and heavy (> 30 g/day) smokers at the first time-point who later reported...... 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...

  1. Biomarkers for early diagnosis of type 2 diabetic nephropathy: a study based on an integrated biomarker system.

    Science.gov (United States)

    Huang, Min; Liang, Qionglin; Li, Ping; Xia, Jianfei; Wang, Yong; Hu, Ping; Jiang, Zhiting; He, Yongxin; Pang, Liqiong; Han, Lida; Wang, Yiming; Luo, Guoan

    2013-08-01

    Diabetic nephropathy is a devastating disease that affects a growing number of diabetic patients. A complete cure is very hard to achieve once the disease has been diagnosed, therefore the diagnosis of early stages in diabetic nephropathy has become a hot area. Numbers of molecules have been proposed to be potential biomarkers for this purpose. However, some problems still remain, such as discovering effective biomarkers to diagnose the disease before obvious clinical evidence appears. Thus, the main purpose of this study was to find plasma biomarkers for early diagnosis of type 2 diabetic nephropathy stage 1 and stage 2, as well as separating them from diabetes. 182 subjects (Chinese) were recruited for this study, including 50 healthy controls, 33 type 2 diabetic patients and 99 type 2 diabetic nephropathy patients (33 of these were stage 3). Important clinical indicators including proteinuria, serum creatinine, and urea nitrogen were measured and the glomerular filtration rate was estimated to assess kidney function; fasting blood glucose, postprandial blood glucose and glycated hemoglobin were measured to assess the blood glucose control. Key metabolites and genes in plasma samples were identified and determined using -omic and quantitative techniques. The potential biomarkers were then combined and carefully screened to determine the most informative ones for early diagnosis of type 2 diabetic nephropathy. An integrated biomarker system (IBS) incorporating 6 clinical indicators, 40 metabolites and 5 genes was established. Correlation analysis results revealed that most of the potential biomarkers significantly correlated with the 6 clinical indicators. Discriminant analysis results showed that the developed IBS gave the highest total predictive accuracy (98.9%). Significant test and receiver operating characteristic analysis results indicated that inosine had the highest sensitivity (0.889), specificity (1.000), positive predictive rate (1.000) and negative

  2. Biomarker response of climate change-induced ocean acidification and hypercapnia studies on brachyurian crab Portunus pelagicus

    Directory of Open Access Journals (Sweden)

    R. Jeevapriya

    2017-04-01

    Full Text Available A laboratory level microcosm analysis of the impacts of ocean acidification on the environmental stress biomarkers in Portunus pelagicus (Linneaus 1758exposed to a series of pH regimes expected in the year 2100 (pH 7.5 and 7.0 and leakage from a sub-seabed carbon dioxide storage site (pH 6.5 - 5.5 was carried out. Levels of the antioxidant enzyme catalase, the phase II detoxification enzyme, glutathione S. transferase, the lipid peroxidation biomarker, malondialdehyde, acetylcholinesterase, and reduced glutathione were estimated in the tissues of the exposed animals to validate theses enzymes as biomarkers of Hypercapnia. The integrated biomarkers indicated a stress full environment in all animals except those exposed to the control seawater (pH 8.1. The reducing pH was also observed to be highly lethal to the animals exposed to lower pH levels which were obvious from the rate of mortality in a short term of exposure. The present study substantiates the role of biomarkers as an early warning of ocean acidification at a sub-lethal level.

  3. Thinking and Creative Styles: A Validity Study

    Science.gov (United States)

    Wechsler, Solange Muglia; Vendramini, Claudette Maria Medeiros; Oakland, Thomas

    2012-01-01

    The validity evidences of thinking and creative styles were analyzed. Two studies are reported, one analyzing the dimensionality of creative styles and the other verifying their external validity. Participants were Brazilians, 1,752 in the first study (55% women) and 128 in the second study (53% women), among whom 45% had demonstrated creative…

  4. Improving low-level plasma protein mass spectrometry-based detection for candidate biomarker discovery and validation

    Energy Technology Data Exchange (ETDEWEB)

    Page, Jason S.; Kelly, Ryan T.; Camp, David G.; Smith, Richard D.

    2008-09-01

    Methods. To improve the detection of low abundance protein candidate biomarker discovery and validation, particularly in complex biological fluids such as blood plasma, increased sensitivity is desired using mass spectrometry (MS)-based instrumentation. A key current limitation on the sensitivity of electrospray ionization (ESI) MS is due to the fact that many sample molecules in solution are never ionized, and the vast majority of the ions that are created are lost during transmission from atmospheric pressure to the low pressure region of the mass analyzer. Two key technologies, multi-nanoelectrospray emitters and the electrodynamic ion funnel have recently been developed and refined at Pacific Northwest National Laboratory (PNNL) to greatly improve the ionization and transmission efficiency of ESI MS based analyses. Multi-emitter based ESI enables the flow from a single source (typically a liquid chromatography [LC] column) to be divided among an array of emitters (Figure 1). The flow rate delivered to each emitter is thus reduced, allowing the well-documented benefits of nanoelectrospray 1 for both sensitivity and quantitation to be realized for higher flow rate separations. To complement the increased ionization efficiency afforded by multi-ESI, tandem electrodynamic ion funnels have also been developed at PNNL, and shown to greatly improve ion transmission efficiency in the ion source interface.2, 3 These technologies have been integrated into a triple quadrupole mass spectrometer for multiple reaction monitoring (MRM) of probable biomarker candidates in blood plasma and show promise for the identification of new species even at low level concentrations.

  5. Hair Measurements of Cortisol, DHEA, and DHEA to Cortisol Ratio as Biomarkers of Chronic Stress among People Living with HIV in China: Known-Group Validation

    Science.gov (United States)

    Li, Xiaoming; Zilioli, Samuele; Chen, Zheng; Deng, Huihua; Pan, Juxian

    2017-01-01

    Background Existing literature suggests that endocrine measures, including the steroid hormones of cortisol and Dehydroepiandrosterone (DHEA), as well as the DHEA to cortisol ratio in the human hair can be used as promising biomarkers of chronic stress among humans. However, data are limited regarding the validity of these measures as biomarkers of chronic stress among people living with HIV (PLWH), whose endocrine system or hypothalamic pituitary adrenal (HPA) axis may be affected by HIV infection and/or antiretroviral therapy (ART) medications. Method Using hair sample data and self-reported survey from 60 PLWH in China, we examined the validity of three endocrine measures among Chinese PLWH using a known-groups validation strategy. High-stress group (n = 30) and low-stress group (n = 30) of PLWH were recruited through individual assessment interviews by a local licensed psychologist. The endocrine measures in hair were extracted and assessed by LC-APCI-MS/MS method. Both bivariate and multivariate analyses were conducted to examine the associations between the endocrine measures and the stress level, and to investigate if the associations differ by ART status. Results The levels of endocrine measures among Chinese PLWH were consistent with existing studies among PLWH. Generally, this pilot study confirmed the association between endocrine measures and chronic stress. The high stress group showed higher level hair cortisol and lower DHEA to cortisol ratio. The higher stress group also reported higher scores of stressful life events, perceived stress, anxiety and depression. Hair cortisol level was positively related to anxiety; DHEA was negatively associated with stressful life events; and the DHEA to cortisol ratio was positively related to stressful life events and perceived stress. ART did not affect the associations between the endocrine measures and stress level. Conclusions Our findings suggest that hair cortisol and DHEA to cortisol ratio can be used as

  6. The past and the future of Alzheimer’s disease CSF biomarkers – a journey towards validated biochemical tests covering the whole spectra of molecular events

    Directory of Open Access Journals (Sweden)

    Kaj eBlennow

    2015-09-01

    Full Text Available This paper gives a short review on cerebrospinal fluid (CSF biomarkers for Alzheimer’s disease (AD, from early developments to high-precision validated assays on fully automated lab analyzers. We also discuss developments on novel biomarkers, such as synaptic proteins and Aβ oligomers. Our vision for the future is that assaying a set of biomarkers in a single CSF tube can monitor the whole spectra of AD molecular pathogenic events. CSF biomarkers will have a central position not only for clinical diagnosis, but also for the understanding of the sequence of molecular events in the pathogenic process underlying AD and as tools to monitor the effects of novel drug candidates targeting these different mechanisms.

  7. Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting

    Energy Technology Data Exchange (ETDEWEB)

    Perani, Daniela [Vita-Salute San Raffaele University, Milan (Italy); San Raffaele Scientific Institute, Division of Neuroscience, Milan (Italy); San Raffaele Hospital, Nuclear Medicine Unit, Milan (Italy); Cerami, Chiara [Vita-Salute San Raffaele University, Milan (Italy); San Raffaele Scientific Institute, Division of Neuroscience, Milan (Italy); San Raffaele Hospital, Clinical Neuroscience Department, Milan (Italy); Caminiti, Silvia Paola [Vita-Salute San Raffaele University, Milan (Italy); San Raffaele Scientific Institute, Division of Neuroscience, Milan (Italy); Santangelo, Roberto; Coppi, Elisabetta; Ferrari, Laura; Magnani, Giuseppe [San Raffaele Hospital, Department of Neurology, Milan (Italy); Pinto, Patrizia [Papa Giovanni XXIII Hospital, Department of Neurology, Bergamo (Italy); Passerini, Gabriella [Servizio di Medicina di Laboratorio OSR, Milan (Italy); Falini, Andrea [Vita-Salute San Raffaele University, Milan (Italy); San Raffaele Scientific Institute, Division of Neuroscience, Milan (Italy); San Raffaele Hospital, CERMAC - Department of Neuroradiology, Milan (Italy); Iannaccone, Sandro [San Raffaele Hospital, Clinical Neuroscience Department, Milan (Italy); Cappa, Stefano Francesco [San Raffaele Scientific Institute, Division of Neuroscience, Milan (Italy); IUSS Pavia, Pavia (Italy); Comi, Giancarlo [Vita-Salute San Raffaele University, Milan (Italy); San Raffaele Hospital, Department of Neurology, Milan (Italy); Gianolli, Luigi [San Raffaele Hospital, Nuclear Medicine Unit, Milan (Italy)

    2016-03-15

    The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI). We evaluated the supportive role of CSF Aβ{sub 42}, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression. Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer's disease and in the differential diagnosis of non-Alzheimer's disease dementias. The p-tau/Aβ{sub 42} ratio was the only CSF biomarker providing a significant classification rate for Alzheimer's disease. An Alzheimer's disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer's disease. In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ{sub 42} ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer's disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role. (orig.)

  8. Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease.

    Science.gov (United States)

    Murugesan, Vagishwari; Liu, Jun; Yang, Ruhua; Lin, Haiquin; Lischuk, Andrew; Pastores, Gregory; Zhang, Xiaokui; Chuang, Wei-Lien; Mistry, Pramod K

    2016-12-13

    In the spleens of Gaucher disease mice and patients, there is a striking elevation of expression of glycoprotein non-Metastatic Melanoma B (gpNMB). We conducted a study in a large cohort of patients with Gaucher disease to assess the utility of serum levels of soluble fragment of gpNMB as a biomarker of disease activity. There was >15-fold elevation of gpNMB in sera of untreated patients with Gaucher disease. gpNMB levels correlated with overall disease severity as well as the severity of individual organ compartments: liver, spleen, bone and hematological disease. Imiglucerase enzyme replacement therapy resulted in significant reduction of gpNMB. Serum levels of gpNMB were highly correlated with accumulation of bioactive lipid substrate of Gaucher disease, glucosylsphingosine as well as established biomarkers, chitotriosidase and chemokine, CCL18. Our results suggest utility of gpNMB as a biomarker of Gaucher disease to monitor individual patients and cohorts of patients for disease progression or response to therapy. Investigation of gpNMB in Gaucher disease pathophysiology is likely to illuminate our understanding disease mechanisms.

  9. 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...... was significantly associated with survival, even after adjustment for chronological age, sex, and rearing environment. Perceived age was still significantly associated with survival after further adjustment for physical and cognitive functioning. The likelihood that the older looking twin of the pair died first...... age, controlled for chronological age and sex, also correlated significantly with physical and cognitive functioning as well as with leucocyte telomere length. CONCLUSION: Perceived age-which is widely used by clinicians as a general indication of a patient's health-is a robust biomarker of ageing...

  10. 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

    play an important role in the reliable measurement of these biomarkers across laboratories. AIM: In this study, we aim to surpass the efforts from previous studies, by employing a multicenter approach to assess the impact of less studied CSF pre-analytical confounders in AD-biomarkers quantification...

  11. Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects.

    Directory of Open Access Journals (Sweden)

    Mark Pimentel

    Full Text Available Diarrhea-predominant irritable bowel syndrome (IBS is diagnosed through clinical criteria after excluding "organic" conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375 were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3. Subjects with inflammatory bowel disease (IBD (n=142, subjects with celiac disease (n=121, and healthy controls (n=43 were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001. Anti-vinculin titers were also significantly higher in IBS (P<0.001 compared to the other groups. The area-under-the-receiver operating curves (AUCs were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density≥2.80 the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD≥1.68 were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and

  12. Reappraisal of OMERACT 8 draft validation criteria for a soluble biomarker reflecting structural damage endpoints in rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis

    DEFF Research Database (Denmark)

    Maksymowych, Walter P; Landewé, Robert; Tak, Paul-Peter

    2009-01-01

    and the principle objectives of the validation process were clarified at a meeting of the working group in London, December 2007. A new framework was proposed after the following steps were conducted: (A) A systematic review of the literature focusing on the draft criteria and a preselected group of biomarkers (MMP...

  13. D-lactate is a valid biomarker of intestinal ischemia induced by abdominal compartment syndrome

    DEFF Research Database (Denmark)

    Nielsen, Casper; Kirkegård, Jakob; Erlandsen, Erland J;

    2015-01-01

    BACKGROUND: Intra-abdominal hypertension (IAH) often leads to abdominal compartment syndrome, which is followed by intestinal ischemia and associated with a high mortality. The diagnosis of abdominal compartment syndrome is difficult, and no valid biochemical markers are available. We conducted...

  14. The use of biomarkers for improved retrospective exposure assessment in epidemiological studies: summary of an ECETOC workshop.

    Science.gov (United States)

    Scheepers, Paul T J

    2008-11-01

    During a scientific workshop the use of biological monitoring in characterization of retrospective exposure assessment was discussed. The workshop addressed currently available methodology and also novel approaches such as in different fields of 'omics'. For use in epidemiology requiring retrospective exposure assessment, biomarker levels should not vary too much over time. If variability in exposure over time is large and differences in exposure between individuals are relatively small, this may lead to underestimation of the exposure-response relationship. This means that, for a sound assessment of health risk, biomarkers that reflect cumulative exposure over a long period of time are preferred over biomarkers with short half-lives. Most of the existing biomarkers such as metabolites in body fluids usually have rather short half-lives, typically less than 1-2 days. Some adducts to DNA show somewhat longer half-lives. The current limit to persistence of biomarkers reflecting cumulative exposure over time is from adducts to haemoglobin with a half-life of 4 months. Some specific organic substances may be more persistent due to storage in adipose tissue or metals in kidneys, nails and hair. The metabonomics, proteomics and present gene expression profiling approaches do not provide a perspective to the availability of more persistent biomarkers and most approaches discussed to date show that it is difficult to interpret study outcomes in terms of exposure to a specific xenobiotic factor. Research efforts should focus on improvement and validation of currently available approaches in the field of addition products to DNA and proteins. Promising new developments may be phosphotriester DNA adducts and adducts to more long-lived proteins such as histones.

  15. Intensive serial biomarker profiling for the prediction of neutropenic fever in patients with hematologic malignancies undergoing chemotherapy: a pilot study

    Directory of Open Access Journals (Sweden)

    Steven M. Chan

    2014-06-01

    Full Text Available Neutropenic fever (NF is a life-threatening complication of myelosuppressive chemotherapy in patients with hematologic malignancies and triggers the administration of broad-spectrum antimicrobials. The ability to accurately predict NF would permit initiation of antimicrobials earlier in the course of infection with the goal of decreasing morbid complications and progression to septic shock and death. Changes in the blood level of inflammatory biomarkers may precede the occurrence of NF. To identify potential biomarkers for the prediction of NF, we performed serial meas- urements of nine biomarkers [C-reactive protein (CRP, protein C, interleukin (IL-6, IL-8, IL-10, IL-1β, tumor necrosis factor-α, monocyte chemotactic protein-1, and intercellular adhesion molecule-1] using a multiplex ELISA array platform every 6-8 hours in patients undergoing myelosuppressive chemotherapy for hematologic malignancies. We found that the blood levels of IL-6 and CRP increased significantly 24 to 48 hours prior to the onset of fever. In addition, we showed that frequent biomarker monitoring is feasible using a bedside micro sample test device. The results of this pilot study suggest that serial monitoring of IL-6 and CRP levels using a bedside device may be useful in the prediction of NF. Prospective studies involving a larger cohort of patients to validate this observation are warranted. This trial is registered at ClinicalTrials.gov (NCT01144793.

  16. 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.

  17. 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

    of studies. This guideline by the BioMS-eu consortium is aimed at setting a standard for the reporting of future body fluid biomarker research studies in neurologic disorders. We anticipate that following these guidelines will help to accelerate the selection of biomarkers for clinical development.......OBJECTIVE: The aim of these guidelines is to make the process of reporting body fluid biomarker studies in neurologic disorders more uniform and transparent, in line with existing standards for reporting research in other biomedical areas. Although biomarkers have been around for decades......-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...

  18. Who to target in sudden unexpected death in epilepsy prevention and how? Risk factors, biomarkers, and intervention study designs.

    Science.gov (United States)

    Tomson, Torbjörn; Surges, Rainer; Delamont, Robert; Haywood, Serena; Hesdorffer, Dale C

    2016-01-01

    The risk of dying suddenly and unexpectedly is increased 24- to 28-fold among young people with epilepsy compared to the general population, but the incidence of sudden unexpected death in epilepsy (SUDEP) varies markedly depending on the epilepsy population. This article first reviews risk factors and biomarkers for SUDEP with the overall aim of enabling identification of epilepsy populations with different risk levels as a background for a discussion of possible intervention strategies. The by far most important clinical risk factor is frequency of generalized tonic-clonic seizures (GTCS), but nocturnal seizures, early age at onset, and long duration of epilepsy have been identified as additional risk factors. Lack of antiepileptic drug (AED) treatment or, in the context of clinical trials, adjunctive placebo versus active treatment is associated with increased risks. Despite considerable research, reliable electrophysiologic (electrocardiography [ECG] or electroencephalography [EEG]) biomarkers of SUDEP risk remain to be established. This is an important limitation for prevention strategies and intervention studies. There is a lack of biomarkers for SUDEP, and until validated biomarkers are found, the endpoint of interventions to prevent SUDEP must be SUDEP itself. These interventions, be they pharmacologic, seizure-detection devices, or nocturnal supervision, require large numbers. Possible methods for assessing prevention measures include public health community interventions, self-management, and more traditional (and much more expensive) randomized clinical trials.

  19. Novel multimetabolite prediction of walnut consumption by a urinary biomarker model in a free-living population: the PREDIMED study.

    Science.gov (United States)

    Garcia-Aloy, Mar; Llorach, Rafael; Urpi-Sarda, Mireia; Tulipani, Sara; Estruch, Ramon; Martínez-González, Miguel A; Corella, Dolores; Fitó, Montserrat; Ros, Emilio; Salas-Salvadó, Jordi; Andres-Lacueva, Cristina

    2014-07-03

    The beneficial impact of walnuts on human health has been attributed to their unique chemical composition. In order to characterize the dietary walnut fingerprinting, spot urine samples from two sets of 195 (training) and 186 (validation) individuals were analyzed by an HPLC-q-ToF-MS untargeted metabolomics approach, selecting the most discriminating metabolites by multivariate data analysis (VIP ≥ 1.5). Stepwise logistic regression analysis was used to design a multimetabolite prediction biomarker model. The global performance of the model and each included metabolite in it was evaluated by receiver operating characteristic curves, using the area under the curve (AUC) values. Dietary exposure to walnuts was characterized by 18 metabolites, including markers of fatty acid metabolism, ellagitannin-derived microbial compounds, and intermediate metabolites of the tryptophan/serotonin pathway. The predictive model of walnut exposure included at least one compound of each class. The AUC (95% CI) for the combined biomarker model was 93.4% (90.1-96.8%) in the training set and 90.2% (85.9-94.6%) in the validation set. The AUCs for individual metabolites were ≤85%. As far as we know, this is the first study proposing a combination of biomarkers of walnut exposure in a population under free-living conditions, as considered in epidemiological studies examining associations between diet and health outcomes.

  20. A Validated High-Let Radiation Specific Biomarker in the Mayak Worker Cohort

    Energy Technology Data Exchange (ETDEWEB)

    David J. Brenner, Ph.D., D.Sc.; Tamara Azizova, M.D.

    2006-12-11

    Our goal (see Project Objectives) is to deliver a dosimetry system which will enable both a Pu body burden of 0.3 kBq, and a 30 cGy {gamma} ray dose, to be separately estimated with a confidence limit of {+-}30%. In terms of the numbers analyzed and the data we have accrued, we have direct quantitative evidence that we are on track to providing such a comprehensive independent dosimetry system for Mayak workers. We had previously demonstrated that intra-chromosomal aberrations measured in peripheral blood lymphocytes can be used as a sensitive long-lived low-background quantitative biomarker of densely-ionizing radiation dose in individuals exposed many years ago. We propose to calibrate the system such that it can be used to estimate both the densely-ionizing internal plutonium exposure and the sparsely-ionizing external exposure in Mayak workers exposed to different combinations of these over a prolonged period, mostly many years ago. Our objective is to deliver a dosimetry system (set of calibration parameters) which will enable both a comparatively low Pu body burden of 0.3 kBq, and a comparatively low 30 cGy {gamma} ray dose (one of these or both of these) to be estimated with a confidence limit of {+-}30% (higher doses will of course be estimated with smaller confidence intervals and still lower doses with larger confidence intervals). (1) Draw blood, make metaphase slides and measure numbers of intra- and inter-chromosome aberrations (using the mBAND and mFISH techniques) in - (A) 255 healthy former Mayak workers who were exposed various combinations of internal and external exposures. The individuals were chosen from the data base of healthy former workers through computer simulation to optimize estimates of the dosimetry parameters. The individuals have both internal and external dose estimates from the SUBI Doses-99 system. (B) 85 healthy non-exposed controls with ages, gender, and smoking status, chosen based on computer simulation to optimize estimates

  1. Validation of differential GDAP1 DNA methylation in alcohol dependence and its potential function as a biomarker for disease severity and therapy outcome.

    Science.gov (United States)

    Brückmann, Christof; Di Santo, Adriana; Karle, Kathrin Nora; Batra, Anil; Nieratschker, Vanessa

    2016-06-02

    Alcohol dependence is a severe disorder contributing substantially to the global burden of disease. Despite the detrimental consequences of chronic alcohol abuse and dependence, effective prevention strategies as well as treatment options are largely missing to date. Accumulating evidence suggests that gene-environment interactions, including epigenetic mechanisms, play a role in the etiology of alcohol dependence. A recent epigenome-wide study reported widespread alterations of DNA methylation patterns in alcohol dependent patients compared to control individuals. In the present study, we validate and replicate one of the top findings from this previous investigation in an independent cohort: the hypomethylation of GDAP1 in patients. To our knowledge, this is the first independent replication of an epigenome-wide finding in alcohol dependence. Furthermore, the AUDIT as well as the GSI score were negatively associated with GDAP1 methylation and we found a trend toward a negative association between GDAP1 methylation and the years of alcohol dependency, pointing toward a potential role of GDAP1 hypomethylation as biomarker for disease severity. In addition, we show that the hypomethylation of GDAP1 in patients reverses during a short-term alcohol treatment program, suggesting that GDAP1 DNA methylation could also serve as a potential biomarker for treatment outcome. Our data add to the growing body of knowledge on epigenetic effects in alcohol dependence and support GDAP1 as a novel candidate gene implicated in this disorder. As the role of GDAP1 in alcohol dependence is unknown, this novel candidate gene should be followed up in future studies.

  2. 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

  3. The emerging science of quantitative imaging biomarkers terminology and definitions for scientific studies and regulatory submissions.

    Science.gov (United States)

    Kessler, Larry G; Barnhart, Huiman X; Buckler, Andrew J; Choudhury, Kingshuk Roy; Kondratovich, Marina V; Toledano, Alicia; Guimaraes, Alexander R; Filice, Ross; Zhang, Zheng; Sullivan, Daniel C

    2015-02-01

    The development and implementation of quantitative imaging biomarkers has been hampered by the inconsistent and often incorrect use of terminology related to these markers. Sponsored by the Radiological Society of North America, an interdisciplinary group of radiologists, statisticians, physicists, and other researchers worked to develop a comprehensive terminology to serve as a foundation for quantitative imaging biomarker claims. Where possible, this working group adapted existing definitions derived from national or international standards bodies rather than invent new definitions for these terms. This terminology also serves as a foundation for the design of studies that evaluate the technical performance of quantitative imaging biomarkers and for studies of algorithms that generate the quantitative imaging biomarkers from clinical scans. This paper provides examples of research studies and quantitative imaging biomarker claims that use terminology consistent with these definitions as well as examples of the rampant confusion in this emerging field. We provide recommendations for appropriate use of quantitative imaging biomarker terminological concepts. It is hoped that this document will assist researchers and regulatory reviewers who examine quantitative imaging biomarkers and will also inform regulatory guidance. More consistent and correct use of terminology could advance regulatory science, improve clinical research, and provide better care for patients who undergo imaging studies.

  4. Identification and Validation of Established and Novel Biomarkers for Infections in Burns

    Science.gov (United States)

    2015-10-01

    PROJECT NUMBER Associate Professor, Department of Surgery The University of Texas Medical Branch at Galveston 5e. TASK NUMBER E-Mail: ccfinner@utmb.edu...include workshops, conferences, seminars , study groups, and individual study. Include participation in conferences, workshops, and seminars not listed...propranolol in treating pediatric burn patients Aims: We will determine the safety and efficacy of administration of propranolol for one year in

  5. 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...

  6. Identification of biomarkers of human pancreatic adenocarcinomas by expression profiling and validation with gene expression analysis in endoscopic ultrasound-guided fine needle aspiration samples

    Institute of Scientific and Technical Information of China (English)

    Henrik Laurell; Louis Buscail; Michèle Bouisson; Philippe Berthelémy; Philippe Rochaix; Sébastien Déjean; Philippe Besse; Christiane Susini; Lucien Pradayrol; Nicole Vaysse

    2006-01-01

    AIM: To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR (RT-QPCR) in endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) specimens.METHODS: Commercially dedicated cancer cDNA macroarrays (Atlas Human Cancer 1.2) containing 1176 genes were used. Different statistical approaches (hierarchical clustering, principal component analysis (PCA) and SAM) were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results.RESULTS: RT-QPCR validated the increased expression of LCN2 (lipocalin 2) and for the first time PLAT (tissue-type plasminogen activator or tPA) in malignant pancreas as compared with normal pancreas.Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique.CONCLUSION: Expression profiling is a useful method to identify biomarkers and potential target genes.Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.

  7. Validation of the Diet Quality Index for Adolescents by Comparison with Biomarkers, Nutrient and Food Intakes

    DEFF Research Database (Denmark)

    Vyncke, Krishna; Cruz Fernandez, Estefania; Fajó-Pascual, Marta

    2013-01-01

    Food-based dietary guidelines (FBDG) aim to address the nutritional requirements at population level in order to prevent diseases and promote a healthy lifestyle. Diet quality indices can be used to assess the compliance with these FBDG. The present study aimed to investigate whether the newly...... in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study. Dietary intake was assessed by two, non-consecutive 24 h recalls. A DQI-A score, considering the components' dietary quality, diversity and equilibrium, was calculated. Associations between the DQI-A and food and nutrient intakes...

  8. Possible Biomarkers of Chronic Stress Induced Exhaustion - A Longitudinal Study.

    Directory of Open Access Journals (Sweden)

    Johanna Wallensten

    Full Text Available Vascular endothelial growth factor (VEGF, epidermal growth factor (EGF and monocyte chemotactic protein-1 (MCP-1 have previously been suggested to be potential biomarkers for chronic stress induced exhaustion. The knowledge about VEGF has increased during the last decades and supports the contention that VEGF plays an important role in stress and depression. There is scarce knowledge on the possible relationship of EGF and MCP-1 in chronic stress and depression. This study further examines the role of VEGF, EGF and MCP-1 in women with chronic stress induced exhaustion and healthy women during a follow-up period of two years.Blood samples were collected from 105 women with chronic stress induced exhaustion on at least 50% sick leave for at least three months, at inclusion (T0, after 12 months (T12 and after 24 months (T24. Blood samples were collected at inclusion (T0 in 116 physically and psychiatrically healthy women. The plasma levels of VEGF, EGF and MCP-1 were analyzed using Biochip Array Technology. Women with chronic stress induced exhaustion had significantly higher plasma levels of VEGF and EGF compared to healthy women at baseline, T12 and at T24. There was no significant difference in plasma levels of MCP-1. Plasma levels of VEGF and EGF decreased significantly in women with chronic stress induced exhaustion during the two years follow-up.The replicated findings of elevated levels of VEGF and EGF in women with chronic stress induced exhaustion and decreasing plasma levels of VEGF and EGF during the two years follow-up add important knowledge to the pathophysiology of chronic stress induced exhaustion.

  9. Biomarkers in Veterinary Medicine.

    Science.gov (United States)

    Myers, Michael J; Smith, Emily R; Turfle, Phillip G

    2017-02-08

    This article summarizes the relevant definitions related to biomarkers; reviews the general processes related to biomarker discovery and ultimate acceptance and use; and finally summarizes and reviews, to the extent possible, examples of the types of biomarkers used in animal species within veterinary clinical practice and human and veterinary drug development. We highlight opportunities for collaboration and coordination of research within the veterinary community and leveraging of resources from human medicine to support biomarker discovery and validation efforts for veterinary medicine.

  10. Biomarkers in Barrett's esophagus.

    Science.gov (United States)

    Reid, Brian J; Blount, Patricia L; Rabinovitch, Peter S

    2003-04-01

    This article provides a framework for clinicians who are attempting the difficult task of interpreting the Barrett's biomarker literature with the goal of improving care for their patients. Although many articles. including more that 60 proposed biomarkers, have been published on this subject, only a few describe phase 3 and 4 studies that are of interest to the clinical gastroenterologist (Table 1). For year, dysplasia grade has been the sole means of risk stratification for patients with BE, and it likely will continue to be used in the foreseeable future. The current authors believe that dysplasia classification can be valuable using the team management approach and quality controls described previously. Significant problems, however, have emerged in phase 2 through 4 studies of dysplasia that make it imperative for the Barrett's field to incorporate additional biomarkers as they are validated. These problems include poor reproducibility of dysplasia interpretations, poor predictive value for negative, indefinite, and low-grade dysplasia, and inconsistent results for HGD in different centers, all of which makes it virtually impossible to develop national guidelines for surveillance. Some studies have even suggested that endoscopic biopsy surveillance using dysplasia may not be worthwhile. Currently, flow cytometric tetraploidy and aneuploidy have progressed furthest in biomarker validation (see Table 1). With proper handling, endoscopic biopsy specimens can be shipped to reference laboratories that have the instruments, computer analytic methods, and expertise to reproducibly detect tetraploidy and aneuploidy. The results of phase 4 studies indicate that flow cytometry appears to be useful in detecting a subset of patients who do not have HGD and yet have an increased risk of progression to cancer that cannot be identified by dysplasia grade. For many reasons, the authors anticipate that the number of validated biomarkers will increase substantially in the

  11. Testing of the preliminary OMERACT validation criteria for a biomarker to be regarded as reflecting structural damage endpoints in rheumatoid arthritis clinical trials: the example of C-reactive protein

    DEFF Research Database (Denmark)

    Keeling, Stephanie O; Landewe, Robert; van der Heijde, Desiree;

    2007-01-01

    OBJECTIVE: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker...

  12. Validity of physiological biomarkers for maternal behavior in cows--a comparison of beef and dairy cattle.

    Science.gov (United States)

    Geburt, Katrin; Friedrich, Morten; Piechotta, Marion; Gauly, Matthias; König von Borstel, Uta

    2015-02-01

    The objectives of the present study were to evaluate the suitability of potential biomarkers for maternal ability in cattle, and in addition to test the hypothesis that dairy cows have a less pronounced motherliness than beef cows. Therefore, maternal behavior of 20 Simmental beef-type (S) and 20 German Black Pied (dairy-type) Cattle (BP) was assessed on the 2nd and again on the 3rd day of the calf's life. Measurements included the frequency of interactions between cow and calf, the cow's willingness to defend her calf, the overall maternal behavior, saliva cortisol, saliva oxytocin, heart rate, and thermal images of the eye (ET). Mixed model analysis revealed that BP had significantly (Poxytocin (88.6±9.2 vs. 62.8±9.2 pg/ml saliva) and cortisol (1.3±0.1 vs. 1.0±0.1 ng/ml saliva) levels, but lower heart rates (80.0±2.0 vs. 95.8±2.0bpm) than S cows. Simmental (beef) cows showed more defensive behavior (3.5±0.2 vs. 2.7±0.2 scores), but fewer total interactions between cow and calf (8.1±1.4 vs. 13.8±1.4), compared to BP (dairy). However, with the exception of heart rate and overall maternal behavior, breed differences tended to diminish from the 2nd to the 3rd day of the calf's life. Repeatabilities ranged from 9±23% (ET) to 77±7% (maternal behavior measured on a visual analogue scale), and correlations between physiological parameters and behavior differed between breeds and were generally at a low level. In conclusion, beef cows do not seem to be per se more maternal compared to dairy cows, and the assessed parameters are of limited use as biomarkers for maternal behavior.

  13. Reliability of Two Diameters Method in Determining Acute Infarct Size. Validation as New Imaging Biomarker.

    Directory of Open Access Journals (Sweden)

    Jochen B Fiebach

    Full Text Available In order to select patients most likely to benefit for thrombolysis and to predict patient outcome in acute ischemic stroke, the volumetric assessment of the infarcted tissue is used. However, infarct volume estimation on Diffusion weighted imaging (DWI has moderate interrater variability despite the excellent contrast between ischemic lesion and healthy tissue. In this study, we compared volumetric measurements of DWI hyperintensity to a simple maximum orthogonal diameter approach to identify thresholds indicating infarct size >70 ml and >100 ml.Patients presenting with ischemic stroke with an NIHSS of ≥ 8 were examined with stroke MRI within 24 h after symptom onset. For assessment of the orthogonal DWI lesion diameters (od-values the image with the largest lesion appearance was chosen. The maximal diameter of the lesion was determined and a second diameter was measured perpendicular. Both diameters were multiplied. Od-values were compared to volumetric measurement and od-value thresholds identifying a lesion size of > 70 ml and > 100 ml were determined. In a selected dataset with an even distribution of lesion sizes we compared the results of the od value thresholds with results of the ABC/2 and estimations of lesion volumes made by two resident physicians.For 108 included patients (53 female, mean age 71.36 years with a median infarct volume of 13.4 ml we found an excellent correlation between volumetric measures and od-values (r2 = 0.951. Infarct volume >100 ml corresponds to an od-value cut off of 42; > 70 ml corresponds to an od-value of 32. In the compiled dataset (n = 50 od-value thresholds identified infarcts > 100 ml / > 70 ml with a sensitivity of 90%/ 93% and with a specificity of 98%/ 89%. The od-value offered a higher accuracy in identifying large infarctions compared to both visual estimations and the ABC/2 method.The simple od-value enables identification of large DWI lesions in acute stroke. The cutoff of 42 is useful to

  14. 'Prediction models for risk of developing type 2 diabetes: systematic literature search and independent external validation study'

    NARCIS (Netherlands)

    Beulens, Joline W J; Abbasi, Ali; Peelen, Linda M; Spijkerman, Annemieke M W; van der A, Daphne L; Corpeleijn, Eva; Bakker, Stephan J L; van der Schouw, Yvonne T

    2013-01-01

    OBJECTIVE: To validate risk scores to predict occurrence of type 2 diabetes in the Dutch population. DESIGN: Prospective cohort study. METHODS: Twelve basic risk scores and 13 extensive risk scores with biomarkers were used to predict the risk of developing type 2 diabetes during 7.5 years in a pros

  15. A Structural and Molecular Approach for the Study Biomarkers

    Science.gov (United States)

    Thomas-Keprta, Kathie; Vali, Hojatollah; Sears, S. Kelly; Roh, Yul

    2001-01-01

    Investigation of the nucleation and growth of crystals in both abiotic and biotic systems is critical to seemingly diverse disciplines of geology, biology, environmental science, and astrobiology. While there are abundant studies devoted to the determination of the structure and composition of inorganic crystals, as well as to the development of thermodynamic and kinetic models, it is only recently that research efforts have been directed towards understanding mineralization in biological systems (i.e., biomineralization). Biomineralization refers to the processes by which living organisms form inorganic solids. Studies of the processes of biomineralization under low temperature aqueous conditions have focused primarily on magnetite forming bacteria and shell forming marine organisms. Many of the biological building materials consist of inorganic minerals (calcium carbonate, calcium phosphate, silica or iron oxide) intricately combined with organic polymers (like proteins). More recently, efforts have been undertaken to explore the nature of biological activities in ancient rocks. In the absence of well-preserved microorganisms or genetic material required for the polmerase chain reaction (PCR) method in molecular phylogenetic studies, using biominerals as biomarkers offers an alternative approach for the recognition of biogenic activity in both terrestrial and extraterrestrial environments. The primary driving force in biomineralization is the interaction between organic and inorganic phases. Thus, the investigation of the ultrastructure and the nature of reactions at the molecular level occurring at the interface between inorganic and organic phases is essential to understanding the processes leading to the nucleation and growth of crystals. It is recognized that crystal surfaces can serve as the substrate for the organization of organic molecules that lead to the formation of polymers and other complex organic molecules, and in discussions of the origins of life

  16. 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 shale...... of other 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....

  17. 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

  18. Protein Complexes in Urine Interfere with Extracellular Vesicle Biomarker Studies

    OpenAIRE

    Magda Wachalska; Danijela Koppers-Lalic; Monique van Eijndhoven; Michiel Pegtel; Geldof, Albert A.; Lipinska, Andrea D.; R. Jeroen van Moorselaar; Irene V. Bijnsdorp

    2016-01-01

    Urine exosomes (extracellular vesicles; EVs) contain (micro)RNA (miRNA) and protein biomarkers that are useful for the non-invasive diagnosis of various urological diseases. However, the urinary Tamm-Horsfall protein (THP) complex, which forms at reduced temperatures, may affect EV isolation and may also lead to contamination by other molecules including microRNAs (miRNAs). There‐ fore, we compared the levels of three miRNAs within the purified EV fraction and THP- protein-network. Urine was ...

  19. Is Abeta a sufficient Biomarker for monitoring anti-Abeta clinical studies? A critical review.

    Directory of Open Access Journals (Sweden)

    Jens eMoreth

    2013-07-01

    Full Text Available Amyloid-beta (Aβ in Alzheimer’s disease (AD appeared to be a promising target for disease-modifying therapeutic strategies like passive immunotherapy with anti-Aβ monoclonal antibodies (mAbs. Biochemical markers in cerebrospinal fluid (CSF include alterations of Aβ that allow the diagnosis of AD. Biomarker strategies, such as the levels of Aβ in CSF and plasma, currently play an important role in early clinical trials for AD. Indeed, these strategies have a relevant impact on the outcome of such studies, since the biomarkers are used to monitor the bioactivity of anti-Aβ mAbs. The clinical trials of Solanezumab were mainly based on the readout of Aβ levels in CSF and plasma, whereas those of Bapineuzumab were based on cognition; however, little is known about the mechanisms altering these biomarker levels, and no biomarker has yet been proven to be a successful predictor for AD therapy. In addition, the Aβ biomarkers allow for the determination of free and bound anti-Aβ mAb in order to monitor the available amount of bioactive drug and could give hints to the mechanism of action. In this review, we discuss clinical Aβ biomarker data and the latest regulatory strategies.

  20. Coherent pipeline for biomarker discovery using mass spectrometry and bioinformatics

    Directory of Open Access Journals (Sweden)

    Al-Shahib Ali

    2010-08-01

    Full Text Available Abstract Background Robust biomarkers are needed to improve microbial identification and diagnostics. Proteomics methods based on mass spectrometry can be used for the discovery of novel biomarkers through their high sensitivity and specificity. However, there has been a lack of a coherent pipeline connecting biomarker discovery with established approaches for evaluation and validation. We propose such a pipeline that uses in silico methods for refined biomarker discovery and confirmation. Results The pipeline has four main stages: Sample preparation, mass spectrometry analysis, database searching and biomarker validation. Using the pathogen Clostridium botulinum as a model, we show that the robustness of candidate biomarkers increases with each stage of the pipeline. This is enhanced by the concordance shown between various database search algorithms for peptide identification. Further validation was done by focusing on the peptides that are unique to C. botulinum strains and absent in phylogenetically related Clostridium species. From a list of 143 peptides, 8 candidate biomarkers were reliably identified as conserved across C. botulinum strains. To avoid discarding other unique peptides, a confidence scale has been implemented in the pipeline giving priority to unique peptides that are identified by a union of algorithms. Conclusions This study demonstrates that implementing a coherent pipeline which includes intensive bioinformatics validation steps is vital for discovery of robust biomarkers. It also emphasises the importance of proteomics based methods in biomarker discovery.

  1. Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue.

    Science.gov (United States)

    Benjachat, Thitima; Tongyoo, Pumipat; Tantivitayakul, Pornpen; Somparn, Poorichaya; Hirankarn, Nattiya; Prom-On, Santitham; Pisitkun, Prapaporn; Leelahavanichkul, Asada; Avihingsanon, Yingyos; Townamchai, Natavudh

    2015-06-23

    The prognosis of severe lupus nephritis (LN) is very different among individual patients. None of the current biomarkers can be used to predict the development of refractory LN. Because kidney histology is the gold standard for diagnosing LN, the authors hypothesize that molecular signatures detected in kidney biopsy tissue may have predictive value in determining the therapeutic response. Sixty-seven patients with biopsy-proven severely active LN by International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification III/IV were recruited. Twenty-three kidney tissue samples were used for RNA microarray analysis, while the remaining 44 samples were used for validation by real-time polymerase chain reaction (PCR) gene expression analysis. From hundreds of differential gene expressions in refractory LN, 12 candidates were selected for validation based on gene expression levels as well as relevant functions. The candidate biomarkers were members of the innate immune response molecules, adhesion molecules, calcium-binding receptors, and paracellular tight junction proteins. S100A8, ANXA13, CLDN19 and FAM46B were identified as the best kidney biomarkers for refractory LN, and COL8A1 was identified as the best marker for early loss of kidney function. These new molecular markers can be used to predict refractory LN and may eventually lead to novel molecular targets for therapy.

  2. Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue

    Directory of Open Access Journals (Sweden)

    Thitima Benjachat

    2015-06-01

    Full Text Available The prognosis of severe lupus nephritis (LN is very different among individual patients. None of the current biomarkers can be used to predict the development of refractory LN. Because kidney histology is the gold standard for diagnosing LN, the authors hypothesize that molecular signatures detected in kidney biopsy tissue may have predictive value in determining the therapeutic response. Sixty-seven patients with biopsy-proven severely active LN by International Society of Nephrology/Renal Pathology Society (ISN/RPS classification III/IV were recruited. Twenty-three kidney tissue samples were used for RNA microarray analysis, while the remaining 44 samples were used for validation by real-time polymerase chain reaction (PCR gene expression analysis. From hundreds of differential gene expressions in refractory LN, 12 candidates were selected for validation based on gene expression levels as well as relevant functions. The candidate biomarkers were members of the innate immune response molecules, adhesion molecules, calcium-binding receptors, and paracellular tight junction proteins. S100A8, ANXA13, CLDN19 and FAM46B were identified as the best kidney biomarkers for refractory LN, and COL8A1 was identified as the best marker for early loss of kidney function. These new molecular markers can be used to predict refractory LN and may eventually lead to novel molecular targets for therapy.

  3. 9th GCC closed forum: CAPA in regulated bioanalysis; method robustness, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, regulatory audit experiences and electronic laboratory notebooks.

    Science.gov (United States)

    Hayes, Roger; LeLacheur, Richard; Dumont, Isabelle; Couerbe, Philippe; Safavi, Afshin; Islam, Rafiq; Pattison, Colin; Cape, Stephanie; Rocci, Mario; Briscoe, Chad; Cojocaru, Laura; Groeber, Elizabeth; Silvestro, Luigi; Bravo, Jennifer; Shoup, Ron; Verville, Manon; Zimmer, Jennifer; Caturla, Maria Cruz; Khadang, Ardeshir; Bourdage, James; Hughes, Nicola; Fatmi, Saadya; Di Donato, Lorella; Sheldon, Curtis; Keyhani, Anahita; Satterwhite, Christina; Yu, Mathilde; Fiscella, Michele; Hulse, James; Lin, Zhongping John; Garofolo, Wei; Savoie, Natasha; Xiao, Yi Qun; Kurylak, Kai; Harris, Sarah; Saxena, Manju; Buonarati, Mike; Lévesque, Ann; Boudreau, Nadine; Lin, Jenny; Khan, Masood U; Ray, Gene; Liu, Yansheng; Xu, Allan; Soni, Gunjan; Ward, Ian; Kingsley, Clare; Ritzén, Hanna; Tabler, Edward; Nicholson, Bob; Bennett, Patrick; van de Merbel, Nico; Karnik, Shane; Bouhajib, Mohammed; Wieling, Jaap; Mulvana, Daniel; Ingelse, Benno; Allen, Mike; Malone, Michele; Fang, Xinping

    2016-03-01

    The 9th GCCClosed Forum was held just prior to the 2015 Workshop on Recent Issues in Bioanalysis (WRIB) in Miami, FL, USA on 13 April 2015. In attendance were 58 senior-level participants, from eight countries, representing 38 CRO companies offering bioanalytical services. The objective of this meeting was for CRO bioanalytical representatives to meet and discuss scientific and regulatory issues specific to bioanalysis. The issues selected at this year's closed forum include CAPA, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, and ELNs. A summary of the industry's best practices and the conclusions from the discussion of these topics is included in this meeting report.

  4. Pupillometry and Saccades as Objective mTBI Biomark

    Science.gov (United States)

    2015-10-01

    1 AWARD NUMBER: W81XWH-14-C-0048 TITLE: Pupillometry and Saccades as Objective mTBI Biomark PRINCIPAL INVESTIGATOR: LTC Jose E. Capo-Aponte...Pupillometry and Saccades as Objective mTBI Biomark 5a. CONTRACT NUMBER W81XWH-14-C-0048 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) LTC... objective biomarkers 14. ABSTRACT The objective of the study is to validate pupillary light reflex (PLR), saccadic and convergence eye movements as

  5. HAND WIPE SUBSAMPLING METHOD FOR USE WITH BIOMARKER MEASUREMENTS IN THE AGRICULTURAL HEALTH STUDY/PESTICIDE EXPOSURE STUDY

    Science.gov (United States)

    Dermal exposure studies incorporating urinary biomarker measurements are complicated because dermal sampling may intercept or remove the target chemical before it is absorbed. A hand wipe subsampling method has been developed using polyurethane foam-tipped (PUF) swabs to minim...

  6. (Very) Early technology assessment and translation of predictive biomarkers in breast cancer.

    Science.gov (United States)

    Miquel-Cases, Anna; Schouten, Philip C; Steuten, Lotte M G; Retèl, Valesca P; Linn, Sabine C; van Harten, Wim H

    2017-01-01

    Predictive biomarkers can guide treatment decisions in breast cancer. Many studies are undertaken to discover and translate these biomarkers, yet few biomarkers make it to practice. Before use in clinical decision making, predictive biomarkers need to demonstrate analytical validity, clinical validity and clinical utility. While attaining analytical and clinical validity is relatively straightforward, by following methodological recommendations, the achievement of clinical utility is extremely challenging. It requires demonstrating three associations: the biomarker with the outcome (prognostic association), the effect of treatment independent of the biomarker, and the differential treatment effect between the prognostic and the predictive biomarker (predictive association). In addition, economical, ethical, regulatory, organizational and patient/doctor-related aspects are hampering the translational process. Traditionally, these aspects do not receive much attention until formal approval or reimbursement of a biomarker test (informed by Health Technology Assessment (HTA)) is at stake, at which point the clinical utility and sometimes price of the test can hardly be influenced anymore. When HTA analyses are performed earlier, during biomarker research and development, they may prevent further development of those biomarkers unlikely to ever provide sufficient added value to society, and rather facilitate translation of the promising ones. Early HTA is particularly relevant for the predictive biomarker field, as expensive medicines are under pressure and the need for biomarkers to guide their appropriate use is huge. Closer interaction between clinical researchers and HTA experts throughout the translational research process will ensure that available data and methodologies will be used most efficiently to facilitate biomarker translation.

  7. 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.

  8. Diagnostic and prognostic epigenetic biomarkers in cancer.

    Science.gov (United States)

    Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

    2015-01-01

    Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

  9. A comparative study of n-alkane biomarker and pollen records: an example from southern China

    Institute of Scientific and Technical Information of China (English)

    ZHENG YanHong; ZHOU WeiJian; XIE ShuCheng; YU XueFeng

    2009-01-01

    We report the results of a comparative study of n-alkane biomarkers and pollens in lacustrine and peat deposits at Dingnan, Jiangxi Province in southern China, and discuss the likely causes for the discrepancy in the interpretations of the n-alkane biomarker and pollen records in terms of climate and vegetation change. The results show that past changes in climate and vegetation revealed by the n-alkane record are not always consistent with the pollen assemblage record in the whole section.Biomarkers do not permit direct identification of the plant family and/or genus and mainly record compositions of local plant remains, while pollens mainly reflect the regional vegetation change. Biomarkers and pollen records complement each other, providing a better picture of local and regional environments. Furthermore, biomarkers are more sensitive than pollen to climatic and vegetational change. Several climatic events are clearly identified by the n-alkane biomarker proxies, such as C31/(C27+C29+C31) ratio and can be correlated to the North Atlantic Heinrich event, B/A, YD and two dry-cool events during the early Holocene such as the periods of 9850 to 9585 cal a B.P. and 8590 to 7920 cal a B.P. These events are consistent with those found in the surrounding regions, suggesting that the regional climate was coupled with global-scale abrupt climatic events. Our results suggest that biomarker and pollen data can record the more detailed climate and vegetation information, thus improving the resolution and precision of vegetation and climate reconstruction.

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

    Institute of Scientific and Technical Information of China (English)

    Gary Kim Kuan Low; Seng Chiew Gan; Shu Cheow Ho

    2015-01-01

    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-WhitneyU 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 hasPvalue < 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.

  11. Combined dementia-risk biomarkers in Parkinson's disease: a prospective longitudinal study.

    Science.gov (United States)

    Compta, Yaroslau; Pereira, Joana B; Ríos, Jose; Ibarretxe-Bilbao, Naroa; Junqué, Carme; Bargalló, Núria; Cámara, Ana; Buongiorno, Mariateresa; Fernández, Manel; Pont-Sunyer, Claustre; Martí, Maria J

    2013-08-01

    Neuropsychological (mostly posterior-cortical) deficits, quantitative magnetic resonance imaging (MRI) atrophy patterns, and low cerebrospinal fluid (CSF) levels of amyloid-β have been separately related to worsening cognition in Parkinson's disease (PD). However, these biomarkers have not been longitudinally assessed in combination as PD-dementia predictors. In this prospective longitudinal study, 27 non-demented PD patients underwent CSF, neuropsychological and 3-T brain-MRI studies at baseline and were re-assessed 18 months later in terms of progression to dementia (primary outcome) and longitudinal neuropsychological and cortical thickness changes (secondary outcomes). At follow-up 11 patients (41%) had progressed to dementia. Lower CSF amyloid-β, worse verbal learning, semantic fluency and visuoperceptual scores, and thinner superior-frontal/anterior cingulate and precentral regions were significant baseline dementia predictors in binary logistic regressions as quantitative and/or dichotomised traits. All participants without baseline biomarker abnormalities remained non-demented whereas all with abnormalities in each biomarker type progressed to dementia, with intermediate risk for those showing abnormalities in a single to two biomarker types (p = 0.006). Both the dementia-outcome and low baseline CSF amyloid-β were prospectively associated with limbic and posterior-cortical neuropsychological decline and frontal, limbic and posterior-cortical thinning from baseline to follow-up. These findings suggest that the combination of CSF amyloid-β, neuropsychological and cortical thickness biomarkers might provide a basis for dementia-risk stratification and progression monitoring in PD.

  12. 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......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......, were stable over 12 months. Use of the ADEPT data should prove useful in defining biological phenotypes to facilitate personalized therapeutic approaches....

  13. Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study.

    Directory of Open Access Journals (Sweden)

    Andrea L Conroy

    require validation in prospective studies to confirm that this group of biomarkers improves the diagnostic accuracy of CM from similar conditions causing fever and altered consciousness.

  14. 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.

  15. 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).

  16. Validation Studies for the Diet History Questionnaire II

    Science.gov (United States)

    Data show that the DHQ I instrument provides reasonable nutrient estimates, and three studies were conducted to assess its validity/calibration. There have been no such validation studies with the DHQ II.

  17. An integrated biomarker, isotopic and palaeoenvironmental study through the Late Permian event at Lusitaniadalen, Spitsbergen

    Science.gov (United States)

    Nabbefeld, Birgit; Grice, Kliti; Twitchett, Richard J.; Summons, Roger E.; Hays, Lindsay; Böttcher, Michael E.; Asif, Muhammad

    2010-03-01

    The largest extinction of the Phanerozoic occurred near the Permian/Triassic (P/Tr) boundary some 252 Ma ago. Several scenarios and drivers have been proposed for this event. Here we report for the first time an integrated study comprising sedimentological data, biomarker distributions/abundances and selected stable carbon and hydrogen isotopes along with bulk isotopes (δ 34S pyrite, δ 13C carb, δ 13C org) for a Late Permian section from Lusitaniadalen, Spitsbergen, Norway. Sedimentological and geochemical data support a marine transgression and collapse of the marine ecosystem in the Late Permian. Strong evidence for waxing and waning of photic zone euxinia throughout the Late Permian is provided by Chlorobiaceae-derived biomarkers (including δ 13C data) and δ 34S pyrite, implying multiple phases of H 2S outgassing and potentially several pulses of extinction. A rapid decrease in abundance of various land-plant biomarkers prior to the marine collapse event indicates a dramatic decline of land-plants during the Late Permian and/or increasing distance from palaeoshoreline as a consequence of sea level rise. Changes in δD of selected biomarkers also suggest a change in source of organic matter (OM) or sea level rise. We also found biomarker and isotopic evidence for a phytoplanktonic bloom triggered by eutrophication as a consequence of the marine collapse. Compound specific isotope analyses (CSIA) of algal and land-plant-derived biomarkers, as well as δ 13C of carbonate and bulk OM provide strong evidence for synchronous changes in δ 13C of marine and atmospheric CO 2, attributed to a 13C-depleted source. The source could be associated with isotopically depleted methane released from the melting of gas clathrates and/or from respired OM, due to collapse of the marine ecosystem.

  18. A pilot study of microRNAs as a new potential biomarkers for hypertension

    Institute of Scientific and Technical Information of China (English)

    LI Jie; HUANG Yu-qing; HUANG Cheng; CAI An-ping; YU Xue-ju; WU Ying; FENG Ying-qing

    2016-01-01

    Background MicroRNAs have recently been considered as biomarkers in several different cardiovascular diseases,however,so far there are no circulating miRNAs data about hypertension.Therefore,the aim of the present pilot study was to identify circulating miRNAs for hypertension biomarkers.Methods Using an Agilent microarray,plasma miRNAs were profiled from plasma samples of 10 patients with untreated essential hypertension and 10 healthy controls.Candidate biomarkers identified in the profiles were subjected to validation by using quantitative PCR in an independent sample set of 20 patients with untreated essential hypertension and 20 healthy controls.Then,we assessed the selected miRNAs for the detection and diagnosis of hypertension from plasma samples of 70 patients with untreated essential hypertension and 20 healthy controls.The Spearman correlation coefficient was used to assessed the selected miRNAs correlations with blood pressure.The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy.Results The expressions of selected 8 miRNAs were investigated independently in plasma samples from 10 hypertension patients and 10 healthy subjects.The levels of circulating miR-30c-5p,miR-133b,miR-29b-3p,miR-29a-3p,miR-29c-3p,miR-30a-3p,miR-let7b-3p expression were significantly down regulated in hypertension group compared with healthy group and the level of hsa-rniR-92b-3p was significantly unregulated between the groups.We used qRT-PCR assay to confirm the expression of 8 candidate miRNAs,miR-30c-5p (P < 0.001),miR-29b-3p (P < 0.001),miR-29a -3p (P =0.027),miR-29c-3p (P < 0.001),miR-92b-3p (P =0.003),miR-30a-3p (P =0.704),miR-133b (P =0.346),andmiR-let7b (P =0.161).The diagnostic accuracy of miR-30c-5p,miR-29b-3p,miR-29a-3p,miR-29c-3p and miR-92b-3p,as measured by AUC,were 0.897,0.90,0.829,0.825 and 0.832,respectively,with all P <0.001.Conclusions The plasma levels of miR-30c-5p,miR-29b-3p,miR-29a-3p,miR-29c-3p and

  19. Performance of survivin mRNA as a biomarker for bladder cancer in the prospective study UroScreen.

    Directory of Open Access Journals (Sweden)

    Georg Johnen

    Full Text Available BACKGROUND: Urinary biomarkers have the potential to improve the early detection of bladder cancer. Most of the various known markers, however, have only been evaluated in studies with cross-sectional design. For proper validation a longitudinal design would be preferable. We used the prospective study UroScreen to evaluate survivin, a potential biomarker that has multiple functions in carcinogenesis. METHODS/RESULTS: Survivin was analyzed in 5,716 urine samples from 1,540 chemical workers previously exposed to aromatic amines. The workers participated in a surveillance program with yearly examinations between 2003 and 2010. RNA was extracted from urinary cells and survivin was determined by Real-Time PCR. During the study, 19 bladder tumors were detected. Multivariate generalized estimation equation (GEE models showed that β-actin, representing RNA yield and quality, had the strongest influence on survivin positivity. Inflammation, hematuria and smoking did not confound the results. Survivin had a sensitivity of 21.1% for all and 36.4% for high-grade tumors. Specificity was 97.5%, the positive predictive value (PPV 9.5%, and the negative predictive value (NPV 99.0%. CONCLUSIONS: In this prospective and so far largest study on survivin, the marker showed a good NPV and specificity but a low PPV and sensitivity. This was partly due to the low number of cases, which limits the validity of the results. Compliance, urine quality, problems with the assay, and mRNA stability influenced the performance of survivin. However, most issues could be addressed with a more reliable assay in the future. One important finding is that survivin was not influenced by confounders like inflammation and exhibited a relatively low number of false-positives. Therefore, despite the low sensitivity, survivin may still be considered as a component of a multimarker panel.

  20. Impact of the 2008-2012 French Alzheimer Plan on the use of cerebrospinal fluid biomarkers in research memory center: the PLM Study.

    Science.gov (United States)

    Gabelle, Audrey; Dumurgier, Julien; Vercruysse, Olivier; Paquet, Claire; Bombois, Stéphanie; Laplanche, Jean-Louis; Peoc'h, Katell; Schraen, Susanna; Buée, Luc; Pasquier, Florence; Hugon, Jacques; Touchon, Jacques; Lehmann, Sylvain

    2013-01-01

    The French Alzheimer's Disease Plan aims, in an unprecedented national effort, to develop research, promote optimal diagnosis, and take better care of patients. In order to evaluate the clinical interest and use of cerebrospinal fluid (CSF) biomarkers, a data-sharing project, the PLM (Paris-North, Lille and Montpellier) study has emerged through collaboration between these memory centers, already involved in this field. The revised Alzheimer's disease (AD) diagnosis criteria include CSF biomarkers, but little is known about their use in routine clinical practice. To evaluate their interest and diagnostic accuracy in routine AD diagnosis, a cohort of 677 patients from Montpellier was first analyzed. The results were then validated through the analysis of a second cohort of 638 patients from Lille and Paris-Nord. Diagnoses of AD and other dementias were established by multidisciplinary expert teams, based on neuropsychological exams and structural brain imaging, blinded from CSF results. CSF amyloid-β, tau, and p-tau concentrations were measured for all patients. Receiver-operating characteristic curves were used to define cut-offs and evaluate the ability of each biomarker to discriminate AD from other diagnoses. We showed that p-tau outperformed other biomarkers for discriminating AD from non-AD patients and presents a clear clinical interest. The other biomarkers also showed relevant variations especially when the differential AD diagnoses were taken into account. Altogether we could demonstrate in both mono-centric and multi-centric cohorts from memory clinics the capacity of CSF biomarkers to discriminate AD from non-AD patients in clinical routine with a high sensitivity and specificity.

  1. 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.

  2. 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

  3. Simple, sensitive, selective and validated spectrophotometric methods for the estimation of a biomarker trigonelline from polyherbal gels

    Science.gov (United States)

    Chopra, Shruti; Motwani, Sanjay K.; Ahmad, Farhan J.; Khar, Roop K.

    2007-11-01

    Simple, accurate, reproducible, selective, sensitive and cost effective UV-spectrophotometric methods were developed and validated for the estimation of trigonelline in bulk and pharmaceutical formulations. Trigonelline was estimated at 265 nm in deionised water and at 264 nm in phosphate buffer (pH 4.5). Beer's law was obeyed in the concentration ranges of 1-20 μg mL -1 ( r2 = 0.9999) in deionised water and 1-24 μg mL -1 ( r2 = 0.9999) in the phosphate buffer medium. The apparent molar absorptivity and Sandell's sensitivity coefficient were found to be 4.04 × 10 3 L mol -1 cm -1 and 0.0422 μg cm -2/0.001A in deionised water; and 3.05 × 10 3 L mol -1 cm -1 and 0.0567 μg cm -2/0.001A in phosphate buffer media, respectively. These methods were tested and validated for various parameters according to ICH guidelines. The detection and quantitation limits were found to be 0.12 and 0.37 μg mL -1 in deionised water and 0.13 and 0.40 μg mL -1 in phosphate buffer medium, respectively. The proposed methods were successfully applied for the determination of trigonelline in pharmaceutical formulations (vaginal tablets and bioadhesive vaginal gels). The results demonstrated that the procedure is accurate, precise, specific and reproducible (percent relative standard deviation dosage forms and dissolution studies.

  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. Image Biomarkers and Precision Medicine: need for validation; Los biomarcadores de imagen y la Medicina de Precision: necesidad de validacion

    Energy Technology Data Exchange (ETDEWEB)

    Marti-Bonmati, L.; Alberich-Bayarri, A.; Garcia Castro, F.

    2016-08-01

    Personalized medicine aims to improve the diagnosis, classification and the best treatment for a particular patient. Today, radiologists are challenged to translate new biological discoveries, the different mechanisms of disease and advances in preclinical research, into a clinical reality through patients, images and their associated parameters. In this article we show how digital medical imaging and computational data processing extract numerous quantitative parameters from the obtained images as virtual biopsies. To be implemented in clinical practice, biomarkers should provide useful and relevant information, improving processes diagnostic, therapeutic and monitoring, for the benefit of patients. (Author)

  6. FETAX interlaboratory validation study: Phase 2 testing

    Energy Technology Data Exchange (ETDEWEB)

    Bantle, J.A. (Oklahoma State Univ., Stillwater, OK (United States). Dept. of Zoology); Burton, D.T. (WYE Research and Educational Center, Queenstown, MD (United States)); Dawson, D.A. (Ashland Univ., OH (United States). Dept. of Biology and Toxicology) (and others)

    1994-10-01

    The Frog Embryo Teratogenesis Assay-Xenopus (FETAX) is a 96-h whole embryo developmental toxicity screening assay that can be used in ecotoxicology and in detecting mammalian developmental toxicants when an in vitro metabolic activation system is employed. A standardized American Society for Testing and Materials (ASTM) guide for the conduct of FETAX has been published along with a companion atlas that helps in embryo staging and identifying malformations. As part of the ASTM process, an interlaboratory validation study was undertaken to evaluate the repeatability and reliability of FETAX. Six different laboratories participated in the study. Each laboratory utilized one technician with the exception of one laboratory, which utilized two independent technicians. In Phase 1, FETAX proved to be more repeatable and reliable than many other bioassays. However, some excessive variation was observed in a few laboratories. Some of this variation may have been due to an initial lack of experience with the assay by some technicians. Phase 2, which is reported here, showed far less intralaboratory and interlaboratory variability than did Phase 1. Nonteratogens such as saccharin and sodium cyclamate showed the most consistent results, whereas more variability was observed for the teratogens caffeine and 5-fluorouracil. Interlaboratory coefficient of variation values for all FETAX end points ranged from 7.3 to 54.7%. The minimum concentration to inhibit growth proved to be the most variable end point for three of the four test chemicals, whereas the LC50 and EC50 (malformation) proved to be less variable.

  7. Inconvenient truth: cancer biomarker development by using proteomics.

    Science.gov (United States)

    Kondo, Tadashi

    2014-05-01

    A biomarker is a crucial tool for measuring the progress of disease and the effects of treatment for better clinical outcomes in cancer patients. Diagnostic, predictive, and prognostic biomarkers are required in various clinical settings. The proteome, a functional translation of the genome, is considered a rich source of biomarkers; therefore, sizable time and funding have been spent in proteomics to develop biomarkers. Although significant progress has been made in technologies toward comprehensive protein expression profiling, and many biomarker candidates published, none of the reported biomarkers have proven to be beneficial for cancer patients. The present deceleration in biomarker research can be attributed to technical limitations. Additional efforts are required to further technical progress; however, there are many examples demonstrating that problems in biomarker research are not so much with the technology but in the study design. In the study of biomarkers for early diagnosis, candidates are screened and validated by comparing cases and controls of similar sample size, and the low prevalence of disease is often ignored. Although it is reasonable to take advantage of multiple rather than single biomarkers when studying diverse disease mechanisms, the annotation of individual components of reported multiple biomarkers does not often explain the variety of molecular events underlying the clinical observations. In tissue biomarker studies, the heterogeneity of disease tissues and pathological observations are often not considered, and tissues are homogenized as a whole for protein extraction. In addition to the challenge of technical limitations, the fundamental aspects of biomarker development in a disease study need to be addressed. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.

  8. 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.

  9. 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.

  10. 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.

  11. 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

    intake (including and excluding fruit and vegetable juices). The study population in the present individual participant data meta-analysis consisted of 526 men and women. Carotenoid, folate and vitamin C concentrations showed a positive relationship with fruit and vegetable intake. Measures...... of performance for the prediction model were calculated using cross-validation. For the prediction model of fruit, vegetable and juice intake, the root mean squared error (RMSE) was 258·0 g, the correlation between observed and predicted intake was 0·78 and the mean difference between observed and predicted...... intake was - 1·7 g (limits of agreement: - 466·3, 462·8 g). For the prediction of fruit and vegetable intake (excluding juices), the RMSE was 201·1 g, the correlation was 0·65 and the mean bias was 2·4 g (limits of agreement: - 368·2, 373·0 g). The prediction models which include the biomarkers...

  12. Identification and Validation of Loa loa Microfilaria-Specific Biomarkers: a Rational Design Approach Using Proteomics and Novel Immunoassays

    Science.gov (United States)

    Drame, Papa M.; Meng, Zhaojing; Bennuru, Sasisekhar; Herrick, Jesica A.; Veenstra, Timothy D.

    2016-01-01

    ABSTRACT Immunoassays are currently needed to quantify Loa loa microfilariae (mf). To address this need, we have conducted proteomic and bioinformatic analyses of proteins present in the urine of a Loa mf-infected patient and used this information to identify putative biomarkers produced by L. loa mf. In total, 70 of the 15,444 described putative L. loa proteins were identified. Of these 70, 18 were L. loa mf specific, and 2 of these 18 (LOAG_16297 and LOAG_17808) were biologically immunogenic. We developed novel reverse luciferase immunoprecipitation system (LIPS) immunoassays to quantify these 2 proteins in individual plasma samples. Levels of these 2 proteins in microfilaremic L. loa-infected patients were positively correlated to mf densities in the corresponding blood samples (r = 0.71 and P filariae. Indeed, the specificity of the LOAG_16297 reverse LIPS assay was 96% (with a sensitivity of 77%). Thus, LOAG_16297 is a very promising biomarker that will be exploited in a quantitative point-of-care immunoassay for determination of L. loa mf densities. PMID:26884435

  13. Alcohol and premature death in Estonian men: a study of forensic autopsies using novel biomarkers and proxy informants

    Directory of Open Access Journals (Sweden)

    Ringmets Inge

    2012-02-01

    study is the information on a wide range of informative alcohol biomarkers, several of which have not been used previously in this sort of post-mortem research study. We have demonstrated, for the first time, the epidemiological value and validity of these novel alcohol biomarkers in post-mortem samples.

  14. 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).

  15. Optimal allocation of resources in a biomarker setting.

    Science.gov (United States)

    Rosner, Bernard; Hendrickson, Sara; Willett, Walter

    2015-01-30

    Nutrient intake is often measured with substantial error both in commonly used surrogate instruments such as a food frequency questionnaire (FFQ) and in gold standard-type instruments such as a diet record (DR). If there is a correlated error between the FFQ and DR, then standard measurement error correction methods based on regression calibration can produce biased estimates of the regression coefficient (λ) of true intake on surrogate intake. However, if a biomarker exists and the error in the biomarker is independent of the error in the FFQ and DR, then the method of triads can be used to obtain unbiased estimates of λ, provided that there are replicate biomarker data on at least a subsample of validation study subjects. Because biomarker measurements are expensive, for a fixed budget, one can use a either design where a large number of subjects have one biomarker measure and only a small subsample is replicated or a design that has a smaller number of subjects and has most or all subjects validated. The purpose of this paper is to optimize the proportion of subjects with replicated biomarker measures, where optimization is with respect to minimizing the variance of ln(λ̂). The methodology is illustrated using vitamin C intake data from the European Prospective Investigation into Cancer and Nutrition study where plasma vitamin C is the biomarker. In this example, the optimal validation study design is to have 21% of subjects with replicated biomarker measures.

  16. Immune Biomarker Response Depends on Choice of Experimental Pain Stimulus in Healthy Adults: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Yenisel Cruz-Almeida

    2012-01-01

    Full Text Available Few studies in healthy subjects have examined the neuroimmune responses associated with specific experimental pain stimuli, while none has measured multiple biomarkers simultaneously. The aim of the present study was to compare the neuro-immune responses following two common experimental pain stimuli: cold pressor test (CPT and focal heat pain (FHP. Eight adults participated in two counterbalanced experimental sessions of FHP or CPT with continuous pain ratings and blood sampling before and 30 minutes after the sessions. Despite similar pain intensity ratings (FHP = 42.2±15.3; CPT = 44.5±34.1; P=0.871, CPT and FHP induced different neuro-immune biomarker responses. CPT was accompanied by significant increases in cortisol (P=0.046 and anti-inflammatory cytokine IL-10 (P=0.043 with significant decreases in several pro-inflammatory mediators (IL-1β (P=0.028, IL-12 (P=0.012, TNF-α (P=0.039, and MCP-1 (P=0.038. There were nonsignificant biomarker changes during the FHP session. There were close to significant differences between the sessions for IL-1β (P=0.081, IFN-γ (P=0.072, and IL-12 (P=0.053 with biomarkers decreasing after CPT and increasing after FHP. There were stronger associations between catastrophizing and most biomarkers after CPT compared to FHP. Our results suggest that CPT is a stressful and painful stimulus, while FHP is mostly a painful stimulus. Thus, each experimental pain stimulus can activate different neuro-immune cascades, which are likely relevant for the interpretation of studies in chronic pain conditions.

  17. Biomarkers for systemic lupus erythematosus.

    Science.gov (United States)

    Ahearn, Joseph M; Liu, Chau-Ching; Kao, Amy H; Manzi, Susan

    2012-04-01

    The urgent need for lupus biomarkers was demonstrated in September 2011 during a Workshop sponsored by the Food and Drug Administration: Potential Biomarkers Predictive of Disease Flare. After 2 days of discussion and more than 2 dozen presentations from thought leaders in both industry and academia, it became apparent that highly sought biomarkers to predict lupus flare have not yet been identified. Even short of the elusive biomarker of flare, few biomarkers for systemic lupus erythematosus (SLE) diagnosis, monitoring, and stratification have been validated and employed for making clinical decisions. This lack of reliable, specific biomarkers for SLE hampers proper clinical management of patients with SLE and impedes development of new lupus therapeutics. As such, the intensity of investigation to identify lupus biomarkers is climbing a steep trajectory, lending cautious optimism that a validated panel of biomarkers for lupus diagnosis, monitoring, stratification, and prediction of flare may soon be in hand.

  18. Design and Methods of the Pan-Canadian Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Nephrotoxicity Study

    Science.gov (United States)

    McMahon, Kelly R.; Rod Rassekh, Shahrad; Schultz, Kirk R.; Pinsk, Maury; Blydt-Hansen, Tom; Mammen, Cherry; Tsuyuki, Ross T.; Devarajan, Prasad; Cuvelier, Geoff D. E.; Mitchell, Lesley G.; Baruchel, Sylvain; Palijan, Ana; Carleton, Bruce C.; Ross, Colin J. D.; Zappitelli, Michael

    2017-01-01

    Background: Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity. Data on biomarkers of acute kidney injury (AKI) and late renal outcomes in children treated with cisplatin are limited. Objective: To describe the design and methods of the pan-Canadian ABLE Nephrotoxicity study, which aims to evaluate urine biomarkers (neutrophil gelatinase–associated lipocalin [NGAL] and kidney injury molecule-1 [KIM-1]) for AKI diagnosis, and determine whether they predict risk of long-term renal outcomes (chronic kidney disease [CKD], hypertension). Design: This is a 3-year observational prospective cohort study. Setting: The study includes 12 Canadian pediatric oncology centers. Patients: The target recruitment goal is 150 patients aged less than 18 years receiving cisplatin. Exclusion criteria: Patients with an estimated glomerular filtration rate (eGFR) renal transplantation at baseline. Measurements: Serum creatinine (SCr), urine NGAL, and KIM-1 are measured during cisplatin infusion episodes (pre-infusion, immediate post-infusion, discharge sampling). At follow-up visits, eGFR, microalbuminuria, and blood pressure are measured and outcomes are collected. Methods: Outcomes: AKI is defined as per SCr criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. CKD is defined as eGFR cancer treatment complications. The Nephrotoxicity study is a novel study of AKI biomarkers in children treated with cisplatin that will greatly inform on late cisplatin renal outcomes and follow

  19. Applications and limitations of inflammatory biomarkers for studies on neurocognitive impairment in HIV infection.

    Science.gov (United States)

    Cassol, Edana; Misra, Vikas; Morgello, Susan; Gabuzda, Dana

    2013-12-01

    Despite reduced prevalence of severe forms of HIV-associated neurocognitive disorders (HAND) on current antiretroviral therapy (ART) regimens, milder forms of neurocognitive impairment (NCI) remain prevalent in HIV-infected populations. These mild forms of HAND consist of subtypes, probably reflecting distinct, though possibly overlapping, pathophysiological mechanisms. Factors associated with HAND in HIV patients with prolonged viral suppression on ART include older age, low nadir CD4, active HCV co-infection, and cardiovascular risk factors, but underlying mechanisms and their relationship to innate immune activation, chronic inflammation, and other features of systemic disease are poorly understood. In this article, we discuss applications and limitations of plasma inflammatory biomarkers for studies on HAND in HIV patients on ART and describe an analysis pipeline to reduce common sources of noise and increase likelihood of identifying relevant inflammatory biomarkers. Clinical covariates and comorbidities that influence inflammatory biomarkers, such as aging, obesity, metabolic abnormalities, HCV co-infection, and substance abuse, are also reviewed. As an example for using this analytic pipeline, we present an exploratory study of 22 plasma inflammatory biomarkers (IFN-α 2b and -γ, 16 cytokines/chemokines, sIL-2R, sCD14, HA, and YKL-40) in a cohort of HIV-infected individuals with advanced disease, frequent HCV co-infection, and viral suppression on ART. The identification of inflammatory biomarkers associated with HAND in HIV+ patients on ART may be useful to distinguish between HAND subtypes with distinct pathophysiology, and is important for achieving a systems-level understanding of the biology of these disorders, developing effective therapies, and evaluating therapeutic outcomes.

  20. Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients

    DEFF Research Database (Denmark)

    Győrffy, Balázs; Lánczky, András; Szállási, Zoltán

    2012-01-01

    was set up using gene expression data and survival information of 1287 ovarian cancer patients downloaded from Gene Expression Omnibus and The Cancer Genome Atlas (Affymetrix HG-U133A, HG-U133A 2.0, and HG-U133 Plus 2.0 microarrays). After quality control and normalization, only probes present on all......). A Kaplan–Meier survival plot was generated and significance was computed. The tool can be accessed online at www.kmplot.com/ovar. We used this integrative data analysis tool to validate the prognostic power of 37 biomarkers identified in the literature. Of these, CA125 (MUC16; P=3.7x10–5, hazard ratio (HR...

  1. Identification and Validation of Loa loa Microfilaria-Specific Biomarkers: a Rational Design Approach Using Proteomics and Novel Immunoassays

    Directory of Open Access Journals (Sweden)

    Papa M. Drame

    2016-02-01

    Full Text Available Immunoassays are currently needed to quantify Loa loa microfilariae (mf. To address this need, we have conducted proteomic and bioinformatic analyses of proteins present in the urine of a Loa mf-infected patient and used this information to identify putative biomarkers produced by L. loa mf. In total, 70 of the 15,444 described putative L. loa proteins were identified. Of these 70, 18 were L. loa mf specific, and 2 of these 18 (LOAG_16297 and LOAG_17808 were biologically immunogenic. We developed novel reverse luciferase immunoprecipitation system (LIPS immunoassays to quantify these 2 proteins in individual plasma samples. Levels of these 2 proteins in microfilaremic L. loa-infected patients were positively correlated to mf densities in the corresponding blood samples (r = 0.71 and P < 0.0001 for LOAG_16297 and r = 0.61 and P = 0.0002 for LOAG_17808. For LOAG_16297, the levels in plasma were significantly higher in Loa-infected (geometric mean [GM], 0.045 µg/ml than in uninfected (P < 0.0001, Wuchereria bancrofti-infected (P = 0.0005, and Onchocerca volvulus-infected (P < 0.0001 individuals, whereas for LOAG_17808 protein, they were not significantly different between Loa-infected (GM, 0.123 µg/ml and uninfected (P = 0.06 and W. bancrofti-infected (P = 0.32 individuals. Moreover, only LOAG_16297 showed clear discriminative ability between L. loa and the other potentially coendemic filariae. Indeed, the specificity of the LOAG_16297 reverse LIPS assay was 96% (with a sensitivity of 77%. Thus, LOAG_16297 is a very promising biomarker that will be exploited in a quantitative point-of-care immunoassay for determination of L. loa mf densities.

  2. Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study.

    Science.gov (United States)

    Kenny, Louise C; Black, Michael A; Poston, Lucilla; Taylor, Rennae; Myers, Jenny E; Baker, Philip N; McCowan, Lesley M; Simpson, Nigel A B; Dekker, Gus A; Roberts, Claire T; Rodems, Kelline; Noland, Brian; Raymundo, Michael; Walker, James J; North, Robyn A

    2014-09-01

    More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks' gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks' gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70-0.77) and 0.68 (0.63-0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia.

  3. Pregnancy-induced gingivitis and OMICS in dentistry: in silico modeling and in vivo prospective validation of estradiol-modulated inflammatory biomarkers.

    Science.gov (United States)

    Gürsoy, Mervi; Zeidán-Chuliá, Fares; Könönen, Eija; Moreira, José C F; Liukkonen, Joonas; Sorsa, Timo; Gürsoy, Ulvi K

    2014-09-01

    Pregnancy-associated gingivitis is a bacterial-induced inflammatory disease with a remarkably high prevalence ranging from 35% to 100% across studies. Yet little is known about the attendant mechanisms or diagnostic biomarkers that can help predict individual susceptibility for rational personalized medicine. We aimed to define inflammatory proteins in saliva, induced or inhibited by estradiol, as early diagnostic biomarkers or target proteins in relation to pregnancy-associated gingivitis. An in silico gene/protein interaction network model was developed by using the STITCH 3.1 with "experiments" and "databases" as input options and a confidence score of 0.700 (high confidence). Salivary estradiol, interleukin (IL)-1β and -8, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-2, -8, and -9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 levels from 30 women were measured prospectively three times during pregnancy and twice during postpartum. In silico analysis revealed that estradiol interacts with IL-1β and -8 by an activation link when the "actions view" was consulted. In saliva, estradiol concentrations associated positively with TIMP-1 and negatively with MPO and MMP-8 concentrations. When the gingival bleeding on probing percentage (BOP%) was included in the model as an effect modifier, the only association, a negative one, was found between estradiol and MMP-8. Throughout gestation, estradiol modulates the inflammatory response by inhibiting neutrophilic enzymes, such as MMP-8. The interactions between salivary degradative enzymes and proinflammatory cytokines during pregnancy suggest promising ways to identify candidate biomarkers for pregnancy-associated gingivitis, and for personalized medicine in the field of dentistry. Finally, we call for greater investments in, and action for biomarker research in periodontology and dentistry that have surprisingly lagged behind in personalized medicine compared to other fields, such as cancer research.

  4. Assessment of mycotoxin exposure in the Belgian population using biomarkers: aim, design and methods of the BIOMYCO study.

    Science.gov (United States)

    Heyndrickx, Ellen; Sioen, Isabelle; Bellemans, Mia; De Maeyer, Mieke; Callebaut, Alfons; De Henauw, Stefaan; De Saeger, Sarah

    2014-01-01

    Mycotoxins are harmful food contaminants. Currently, human exposure assessment to these toxins is often based on calculations combining mycotoxin occurrence data in food with population data on food consumption. Because of limitations inherent to that approach, biomarkers have been proposed as a suitable alternative whereby a more accurate assessment of exposure at the individual level can be performed. The BIOMYCO study is designed to assess human mycotoxin exposure using urinary biomarkers of exposure. Over the different seasons of 2013 and 2014, morning urine is gathered in a representative part of the Belgian population according to a designed study protocol, whereby 140 children (3-12 years old) and 278 adults (19-65 years old) are selected based on random cluster sampling stratified for sex, age and geographical areas. Every participant completes a food frequency questionnaire to assess the consumption of relevant foodstuffs (n = 43) of both the day before the urine collection and the previous month. Validated multi-toxin LC-MS/MS methods are used to analyse aflatoxins, fumonisins, ochratoxin A, trichothecenes, zearalenone and their metabolites in morning urine. The study protocol is approved by the ethical committee of the Ghent University Hospital. Within this paper, study design and methods are described. The BIOMYCO study is the first study whereby a multi-toxin approach is applied for mycotoxin exposure assessment in adults and children on a large scale. Moreover, it is the first study that will describe the exposure to an elaborated set of mycotoxins in the Belgian population. In first instance, descriptive analysis will be performed, describing the exposure to mycotoxins for the child and adult group. Exposure of different subgroups will be compared. Furthermore, correlations between the mycotoxin concentrations measured and the food consumption reported will be estimated to explore whether the mycotoxin exposure could be explained by the consumption

  5. Biomarkers of acute lung injury: worth their salt?

    Directory of Open Access Journals (Sweden)

    Proudfoot Alastair G

    2011-12-01

    Full Text Available Abstract The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.

  6. Predicting missing biomarker data in a longitudinal study of Alzheimer disease

    Science.gov (United States)

    Jagust, William J.; Aisen, Paul; Jack, Clifford R.; Toga, Arthur W.; Beckett, Laurel; Gamst, Anthony; Soares, Holly; C. Green, Robert; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Bandy, Dan; Chen, Kewei; Morris, John; Lee, Virginia M.-Y.; Korecka, Magdalena; Crawford, Karen; Neu, Scott; Harvey, Danielle; Kornak, John; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Buckholtz, Neil; Kaye, Jeffrey; Dolen, Sara; Quinn, Joseph; Schneider, Lon; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Tang, Cheuk; Marzloff, George; Toledo-Morrell, Leylade; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn S.; Pedroso, Julia; Toroney, Jaimie; Rusinek, Henry; de Leon, Mony J; De Santi, Susan M; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Aiello, Marilyn; Clark, Christopher M.; Pham, Cassie; Nunez, Jessica; Smith, Charles D.; Given, Curtis A.; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Ismail, M. Saleem; Brand, Connie; Richard, Jennifer; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Diaz-Arrastia, Ramon; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Laubinger, Mary M.; Bartzokis, George; Silverman, Daniel H.S.; Lu, Po H.; Graff-Radford MBBCH, Neill R; Parfitt, Francine; Johnson, Heather; Farlow, Martin; Herring, Scott; Hake, Ann M.; van Dyck, Christopher H.; MacAvoy, Martha G.; Benincasa, Amanda L.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Graham, Simon; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Wu, Chuang-Kuo; Johnson, Nancy; Mesulam, Marsel; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Scott; Johnson, Kathleen B.; Behan, Kelly E.; Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.; Rosen, Allyson; Tinklenberg, Jared; Ashford, Wes; Sabbagh, Marwan; Connor, Donald; Jacobson, Sandra; Killiany, Ronald; Norbash, Alexander; Nair, Anil; Obisesan, Thomas O.; Jayam-Trouth, Annapurni; Wang, Paul; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; DeCarli, Charles; Fletcher, Evan; Carmichael, Owen; Kittur, Smita; Mirje, Seema; Borrie, Michael; Lee, T-Y; Bartha, Dr Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Hendin, Barry A.; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Gandy, Sam; Marenberg, Marjorie E.; Rovner, Barry W.; Pearlson, Godfrey; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Englert, Jessica; Williamson, Jeff D.; Sink, Kaycee M.; Watkins, Franklin; Ott, Brian R.; Wu, Chuang-Kuo; Cohen, Ronald; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo

    2012-01-01

    Objective: To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD). Methods: The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI. Results: CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ42. Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD. Conclusion: The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD. PMID:22491869

  7. College of the Canyons Predictive Validity Studies.

    Science.gov (United States)

    College of the Canyons, Valencia, CA. Office of Institutional Development.

    Matriculation regulations in California require that community colleges which adopt standardized placement tests demonstrate that the tests are valid predictors of future course success. A positive correlation of at least .35 between test score and subsequent student performance in a particular course is needed to demonstrate the predictive…

  8. A critique of biomarkers in environmental toxicology: A case study in birds

    Energy Technology Data Exchange (ETDEWEB)

    Bellward, G.D. [Univ. of British Columbia, Vancouver, British Columbia (Canada)

    1995-12-31

    The authors have been testing the hypothesis that exposure to elevated levels of 2,3,7,8-TCDD and similarly-acting compounds derived from pulp mill effluent adversely affects the reproductive capacity of colonies of great blue herons and double crested cormorants in the local area. Their objectives included developing quantitative TCDD dose-response curves for various toxicologically relevant endpoints in birds, with the goal of finding an appropriate environmental biomarker of dioxin exposure and toxicity. Potential biomarkers studied included ethoxyresorufin O-deethylase (EROD) as a measure of cytochrome P-450 1-A activity, and various hormonally-relevant end-points as measures of dioxin toxicity. The animal model used was the newly hatched chick, after in ovo exposure either in the laboratory or from the environment. Because the TEQ approach is based to a large extent on the use of in vitro and in vivo biomarkers, this study provides a useful example of one of the simplest in vivo models. The authors were able to construct hepatic EROD dose-response curves from the environmentally exposed heron and cormorant chicks, and from TCDD egg injections both early and late in the incubation period. Domestic chicken and pigeons were used as control species. The EROD induction data from the late injection pigeon study was very helpful for predicting appropriate doses for use in the early injection experiments, and for the wild avian species. However, the data was too limited to use for accurately predicting such endpoints as mortality, or effects at the lower end of the dose-response curves. Using various toxic equivalency factors, TEQs for the environmental data were calculated, and compared to the laboratory derived dose-response curves for TCDD. Using specific examples from this environmental case study, the strengths and weaknesses of the use of biomarkers and the TEQ approach will be discussed.

  9. The use of non destructive biomarkers in the study of marine mammals.

    Science.gov (United States)

    M Cristina Fossi And Letizia Marsili

    1997-01-01

    Marine mammals have been subject to heavy anthropogenic pressure by direct killing and chemical pollution all over the world. Most studies of contamination and biomarker responses in marine mammals have been conducted using animals killed by hunting out of a total of 12 cetacean species studied, 45 of the specimens were obtained by sacrificing the animal; out of a total of eight pinniped species studied, 40 of the specimens were obtained by killing. The development of a series of non destructive techniques to evaluate biomarker responses and residue levels is recommended for the hazard assessment and conservation of endangered species of marine mammals. Here we review the current status of the non destructive biomarker approach in marine mammals, describing the biological materials available for non destructive tests in stranded brain, liver, blood, skin, subcutaneous blubber, muscle and fur and free ranging animals blood, skin biopsy, fur and faeces and the respective biomarker techniques mixed function oxidase activity and DNA damage in skin biopsy samples; porphyrins in faeces and fur; esterases, porphyrins, clinical biochemical parameter, vitamin A and micronuclei in blood samples. Residue analysis can be carried out in the various biological materials. We also report the results of applying this methodological approach to cetaceans minke whale Balaenoptera acutorostrata, fin whale-- Balaenoptera physalus, beluga whale-- Delphinapterus leucas, short finned pilot whale-- Globicephala macrorhynchus, harbour porpoise -- Phocoena phocoena, Rissos dolphin-- Risso s Grampus griseus, Dall s porpoise-- Phocoenoides dalli dalli, melon headed whale-- Peponocephala electra, bottlenose dolphin -- Tursiops truncatus, striped dolphin-- Stenella coeruleoalba, spinner dolphin-- Stenella longirostris, killer whale-- Orcinus orca and pinnipeds northern fur seal- Callorhinus ursinus, hooded seal-- Cystophora cristata, grey seal-- Halichoerus grypus, harbour seal-- Phoca vitulina

  10. Enabling Metabolomics Based Biomarker Discovery Studies Using Molecular Phenotyping of Exosome-Like Vesicles.

    Directory of Open Access Journals (Sweden)

    Tatiana Altadill

    Full Text Available Identification of sensitive and specific biomarkers with clinical and translational utility will require smart experimental strategies that would augment expanding the breadth and depth of molecular measurements within the constraints of currently available technologies. Exosomes represent an information rich matrix to discern novel disease mechanisms that are thought to contribute to pathologies such as dementia and cancer. Although proteomics and transcriptomic studies have been reported using Exosomes-Like Vesicles (ELVs from different sources, exosomal metabolome characterization and its modulation in health and disease remains to be elucidated. Here we describe methodologies for UPLC-ESI-MS based small molecule profiling of ELVs from human plasma and cell culture media. In this study, we present evidence that indeed ELVs carry a rich metabolome that could not only augment the discovery of low abundance biomarkers but may also help explain the molecular basis of disease progression. This approach could be easily translated to other studies seeking to develop predictive biomarkers that can subsequently be used with simplified targeted approaches.

  11. New sepsis biomarkers

    Directory of Open Access Journals (Sweden)

    Dolores Limongi

    2016-06-01

    Full Text Available Sepsis remains a leading cause of death in the intensive care units and in all age groups worldwide. Early recognition and diagnosis are key to achieving improved outcomes. Therefore, novel biomarkers that might better inform clinicians treating such patients are surely needed. The main attributes of successful biomarkers would be high sensitivity, specificity, possibility of bedside monitoring and financial accessibility. A panel of sepsis biomarkers along with currently used laboratory tests will facilitate earlier diagnosis, timely treatment and improved outcome may be more effective than single biomarkers. In this review, we summarize the most recent advances on sepsis biomarkers evaluated in clinical and experimental studies.

  12. New sepsis biomarkers

    Institute of Scientific and Technical Information of China (English)

    Dolores Limongi; Cartesio D’Agostini; Marco Ciotti

    2016-01-01

    Sepsis remains a leading cause of death in the intensive care units and in all age groups worldwide. Early recognition and diagnosis are key to achieving improved outcomes.Therefore, novel biomarkers that might better inform clinicians treating such patients are surely needed. The main attributes of successful biomarkers would be high sensitivity,specificity, possibility of bedside monitoring and financial accessibility. A panel of sepsis biomarkers along with currently used laboratory tests will facilitate earlier diagnosis,timely treatment and improved outcome may be more effective than single biomarkers. In this review, we summarize the most recent advances on sepsis biomarkers evaluated in clinical and experimental studies.

  13. New sepsis biomarkers

    Institute of Scientific and Technical Information of China (English)

    Dolores Limongi; Cartesio DAgostini; Marco Ciotti

    2016-01-01

    Sepsis remains a leading cause of death in the intensive care units and in all age groups worldwide. Early recognition and diagnosis are key to achieving improved outcomes. Therefore, novel biomarkers that might better inform clinicians treating such patients are surely needed. The main attributes of successful biomarkers would be high sensitivity, specificity, possibility of bedside monitoring and financial accessibility. A panel of sepsis biomarkers along with currently used laboratory tests will facilitate earlier diagnosis, timely treatment and improved outcome may be more effective than single biomarkers. In this review, we summarize the most recent advances on sepsis biomarkers evaluated in clinical and experimental studies.

  14. The use of S-phenylmercapturic acid as a biomarker in molecular epidemiology studies of benzene.

    Science.gov (United States)

    Farmer, Peter B; Kaur, Balvinder; Roach, Jonathan; Levy, Len; Consonni, Dario; Bertazzi, Pietro A; Pesatori, Angela; Fustinoni, Silvia; Buratti, Marina; Bonzini, Matteo; Colombi, Antonio; Popov, Todor; Cavallo, Domenico; Desideri, Arianna; Valerio, Federico; Pala, Mauro; Bolognesi, Claudia; Merlo, Franco

    2005-05-30

    S-Phenylmercapturic acid (S-PMA), is a urinary metabolite of benzene, thought to be derived from the condensation product of benzene oxide with glutathione. S-PMA may be determined by GC, HPLC (UV or fluorescence detection), GC-MS, LC-MS/MS or immunoassays. The limit of sensitivities of most of these techniques is 1 microg/l urine or below. It has been suggested that S-PMA may have value as a biomarker for low level human exposure to benzene, in view of the facts that urinary excretion of S-PMA has been found to be related to airborne benzene in occupationally exposed workers, and that only low background levels of S-PMA have been found in control subjects. We have evaluated the use of S-PMA as a biomarker, using a commercially available analytical service, in a multicentre European study of populations exposed to varying levels of benzene, in Italy (Milan, Genoa) and in Bulgaria (Sofia). These were filling station attendants, urban policemen, bus drivers, petrochemical workers and referents (a total of 623 subjects). S-PMA was measured at the end of the work shift by an immunoassay procedure. Urinary benzene (in Milan only) and the benzene metabolite trans,trans-muconic acid (t,t-MA) were measured before and after the work shift. Air-borne benzene was measured as a monitor of exposure. Urinary benzene was the most discriminatory biomarker and showed a relationship with airborne benzene at all levels of exposure studied (including groups exposed to <0.1 ppm benzene), whereas t,t-MA and S-PMA, as determined by immunoassay, were suitable only in the highest exposed workers (petrochemical industry, geometric mean 1765 microg/m3 (0.55 ppm) benzene). All three biomarkers were positively correlated with smoking as measured by urinary cotinine).

  15. 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

  16. Searching for non-genetic molecular and imaging PTSD risk and resilience markers: Systematic review of literature and design of the German Armed Forces PTSD biomarker study.

    Science.gov (United States)

    Schmidt, Ulrike; Willmund, Gerd-Dieter; Holsboer, Florian; Wotjak, Carsten T; Gallinat, Jürgen; Kowalski, Jens T; Zimmermann, Peter

    2015-01-01

    Biomarkers allowing the identification of individuals with an above average vulnerability or resilience for posttraumatic stress disorder (PTSD) would especially serve populations at high risk for trauma exposure like firefighters, police officers and combat soldiers. Aiming to identify the most promising putative PTSD vulnerability markers, we conducted the first systematic review on potential imaging and non-genetic molecular markers for PTSD risk and resilience. Following the PRISMA guidelines, we systematically screened the PubMed database for prospective longitudinal clinical studies and twin studies reporting on pre-trauma and post-trauma PTSD risk and resilience biomarkers. Using 25 different combinations of search terms, we retrieved 8151 articles of which we finally included and evaluated 9 imaging and 27 molecular studies. In addition, we briefly illustrate the design of the ongoing prospective German Armed Forces (Bundeswehr) PTSD biomarker study (Bw-BioPTSD) which not only aims to validate these previous findings but also to identify novel and clinically applicable molecular, psychological and imaging risk, resilience and disease markers for deployment-related psychopathology in a cohort of German soldiers who served in Afghanistan.

  17. Digital Learning Literacies – A Validation Study

    Directory of Open Access Journals (Sweden)

    Gila Kurtz

    2016-05-01

    As can be concluded from the findings, most of the participants evaluate themselves as digitally literate with regard to the basic information research and retrieval skills, validation and information management. But when it comes to PSs that require complex decision making or higher order thinking strategies, it seems that a large number of participants lack these skills. Also, social responsibility and digital integrity domains are perceived as known by the participants but not very well taken in terms of pro-active action to enforce appropriate digital behavior, or avoiding illegally obtained music or movies.

  18. Biomarkers of intermediate endpoints in environmental and occupational health

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E; Hansen, Ase M

    2007-01-01

    aberrations (CA), sister chromatid exchanges and micronuclei (MN). The validation of biomarkers includes measurements of sensitivity and specificity of biomarkers and round robin tests to ensure reproducible protocols within different laboratories. The predictive value of biomarkers with respect to adverse...

  19. Neurofilament ELISA validation.

    NARCIS (Netherlands)

    Petzold, A.; Altintas, A.; Andreoni, L.; Bartos, A.; Berthele, A.; Blankenstein, M.A.; Buee, L.; Castellazzi, M.; Cepok, S.; Comabella, M.; Constantinescu, C.S.; Deisenhammer, F.; Deniz, G.; Erten, G.; Espino, M.; Fainardi, E.; Franciotta, D.; Freedman, M.S.; Giedraitis, V.; Gilhus, N.E.; Giovannoni, G.; Glabinski, A.; Grieb, P.; Hartung, H.P.; Hemmer, B.; Herukka, S.K.; Hintzen, R.; Ingelsson, M.; Jackson, S.; Jacobsen, S.; Jafari, N.; Jalosinski, M.; Jarius, S.; Kapaki, E.; Kieseier, B.C.; Koel-Simmelink, M.J.; Kornhuber, J.; Kuhle, J.; Kurzepa, J.; Lalive, P.H.; Lannfelt, L.; Lehmensiek, V.; Lewczuk, P.; Livrea, P.; Marnetto, F.; Martino, D.; Menge, T.; Norgren, N.; Papuc, E.; Paraskevas, G.P.; Pirttila, T.; Rajda, C.; Rejdak, K.; Ricny, J.; Ripova, D.; Rosengren, L.; Ruggieri, M.; Schraen, S.; Shaw, G.; Sindic, C.; Siva, A.; Stigbrand, T.; Stonebridge, I.; Topcular, B.; Trojano, M.; Tumani, H.; Twaalfhoven, H.A.; Vecsei, L.; Pesch, V. Van; Stichele, H. van der; Vedeler, C.; Verbeek, M.M.; Villar, L.M.; Weissert, R.; Wildemann, B.; Yang, C.; Yao, K.; Teunissen, C.E.

    2010-01-01

    BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light

  20. Ecological relevance of biomarkers in monitoring studies of macro-invertebrates and fish in Mediterranean rivers.

    Science.gov (United States)

    Colin, Nicole; Porte, Cinta; Fernandes, Denise; Barata, Carlos; Padrós, Francesc; Carrassón, Maite; Monroy, Mario; Cano-Rocabayera, Oriol; de Sostoa, Adolfo; Piña, Benjamín; Maceda-Veiga, Alberto

    2016-01-01

    Mediterranean rivers are probably one of the most singular and endangered ecosystems worldwide due to the presence of many endemic species and a long history of anthropogenic impacts. Besides a conservation value per se, biodiversity is related to the services that ecosystems provide to society and the ability of these to cope with stressors, including climate change. Using macro-invertebrates and fish as sentinel organisms, this overview presents a synthesis of the state of the art in the application of biomarkers (stress and enzymatic responses, endocrine disruptors, trophic tracers, energy and bile metabolites, genotoxic indicators, histopathological and behavioural alterations, and genetic and cutting edge omic markers) to determine the causes and effects of anthropogenic stressors on the biodiversity of European Mediterranean rivers. We also discuss how a careful selection of sentinel species according to their ecological traits and the food-web structure of Mediterranean rivers could increase the ecological relevance of biomarker responses. Further, we provide suggestions to better harmonise ecological realism with experimental design in biomarker studies, including statistical analyses, which may also deliver a more comprehensible message to managers and policy makers. By keeping on the safe side the health status of populations of multiple-species in a community, we advocate to increase the resilience of fluvial ecosystems to face present and forecasted stressors. In conclusion, this review provides evidence that multi-biomarker approaches detect early signs of impairment in populations, and supports their incorporation in the standardised procedures of the Water Frame Work Directive to better appraise the status of European water bodies.

  1. Circulating biomarkers in acute myofascial pain: A case-control study.

    Science.gov (United States)

    Grosman-Rimon, Liza; Parkinson, William; Upadhye, Suneel; Clarke, Hance; Katz, Joel; Flannery, John; Peng, Philip; Kumbhare, Dinesh

    2016-09-01

    The aims of the present study were to compare levels of circulating inflammatory biomarkers and growth factors between patients with myofascial pain syndrome (MPS) and healthy control participants, and to assess the relationship among inflammatory markers and growth factors in the two groups.Biomarkers levels were assessed in patients (n = 37) with myofascial pain complaints recruited from the hospital emergency department and non-MPS controls (n = 21), recruited via advertisements in the hospital and community.Blood levels of the cytokines, namely, interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-12 (IL-12), and the chemokine, namely, monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine (MDC), eotaxin, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-8 (IL-8), and macrophage inflammatory proteins-1β (MIP-1β) were significantly higher in patients with MPS than controls. The results of the growth factor analyses revealed significantly higher levels of fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) in MPS patients versus controls. The pattern of correlation coefficients between cytokines and growth factors differed considerably for MPS patients and controls with far fewer significant positive coefficients observed in the controls. Serum inflammatory and growth factor biomarkers were elevated in MPS patients.Inflammatory biomarkers and growth factor levels may play an important role in the onset and maintenance of MPS and therefore may be useful in the diagnosis and treatment of MPS. Understanding the mechanisms of inflammation in MPS necessitates future research.

  2. A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker

    Science.gov (United States)

    Khoja, L; Backen, A; Sloane, R; Menasce, L; Ryder, D; Krebs, M; Board, R; Clack, G; Hughes, A; Blackhall, F; Valle, J W; Dive, C

    2012-01-01

    Background: Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet needs. We compared prospectively the utility of two platforms for CTC enumeration and characterisation in pancreatic cancer patients in a pilot exploratory study. Patients and methods: Blood samples were obtained prospectively from 54 consenting patients and analysed by CellSearch and isolation by size of epithelial tumour cells (ISET). CellSearch exploits immunomagnetic capture of CTCs-expressing epithelial markers, whereas ISET is a marker independent, blood filtration device. Circulating tumour cell expression of epithelial and mesenchymal markers was assessed to explore any discrepancy in CTC number between the two platforms. Results: ISET detected CTCs in more patients than CellSearch (93% vs 40%) and in higher numbers (median CTCs/7.5 ml, 9 (range 0–240) vs 0 (range 0–144)). Heterogeneity observed for epithelial cell adhesion molecule, pan-cytokeratin (CK), E-Cadherin, Vimentin and CK 7 expression in CTCs may account for discrepancy in CTC number between platforms. Conclusion: ISET detects more CTCs than CellSearch and offers flexible CTC characterisation with potential to investigate CTC biology and develop biomarkers for pancreatic cancer patient management. PMID:22187035

  3. 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.

  4. The Role of Epigenomics in the Study of Cancer Biomarkers and in the Development of Diagnostic Tools.

    Science.gov (United States)

    Verma, Mukesh

    2015-01-01

    Epigenetics plays a key role in cancer development. Genetics alone cannot explain sporadic cancer and cancer development in individuals with no family history or a weak family history of cancer. Epigenetics provides a mechanism to explain the development of cancer in such situations. Alterations in epigenetic profiling may provide important insights into the etiology and natural history of cancer. Because several epigenetic changes occur before histopathological changes, they can serve as biomarkers for cancer diagnosis and risk assessment. Many cancers may remain asymptomatic until relatively late stages; in managing the disease, efforts should be focused on early detection, accurate prediction of disease progression, and frequent monitoring. This chapter describes epigenetic biomarkers as they are expressed during cancer development and their potential use in cancer diagnosis and prognosis. Based on epigenomic information, biomarkers have been identified that may serve as diagnostic tools; some such biomarkers also may be useful in identifying individuals who will respond to therapy and survive longer. The importance of analytical and clinical validation of biomarkers is discussed, along with challenges and opportunities in this field.

  5. Validation study on avermectine residues in foodstuffs.

    Science.gov (United States)

    Giannetti, L; Giorgi, A; Necci, F; Ferretti, G; Buiarelli, F; Neri, B

    2011-08-26

    Avermectines are antiparasitic agents widely used as veterinary drugs for food producing animals. The European Community, due to their side effects, limited the use of these molecules establishing maximum residue limits (MRLs) in some foods. A validated qualitative and quantitative high performance liquid chromatography method with fluorescence detection (HPLC-FL) is presented for the simultaneous determination of ivermectin (IVM), abemectin (ABA), moxidectin (MOX), eprinomectin (EPR), doramectin (DOR) and emamectin (EMA) in foodstuffs (muscle, eggs and milk). Samples were extracted with acetonitrile, purified with liquid-liquid extraction (LLE), and analysed by HLPC-FL previous derivatization with trifluoroacetic anhydride (TFAA) in presence of 1-methyl-imidazole (MI) and acetic acid. To date, the presented method is the first validated for the matrix eggs, and in accordance with the requirements set by Commission Decision 2002/657/EC. Recoveries of the methods, calculated spiking the samples in the range 5.0-100.0 μg kg(-1), were 64-83% for muscle, 65-89% for milk and 63-84% for eggs. The precision (CV) ranged between 9.2 and 17.1% for muscle, 9.9 and 16.6% for milk and from 9.4 to 17.4% for eggs. Linearity for the six analytes was calculated from 5.0 to 200.0 μg kg(-1). The main advantages of the presented method are its rapidity, the specificity, the good precision and recovery that make it very suitable to the detection and determination of avermectines.

  6. ‘Omics’ biomarkers associated with chronic low back pain: protocol of a retrospective longitudinal study

    Science.gov (United States)

    Allegri, Massimo; 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

    2016-01-01

    Introduction 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. Methods and analysis 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. Ethics and dissemination 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

  7. Analysis of biomarker data a practical guide

    CERN Document Server

    Looney, Stephen W

    2015-01-01

    A "how to" guide for applying statistical methods to biomarker data analysis Presenting a solid foundation for the statistical methods that are used to analyze biomarker data, Analysis of Biomarker Data: A Practical Guide features preferred techniques for biomarker validation. The authors provide descriptions of select elementary statistical methods that are traditionally used to analyze biomarker data with a focus on the proper application of each method, including necessary assumptions, software recommendations, and proper interpretation of computer output. In addition, the book discusses

  8. Sensitivity of two biomarkers for biomonitoring exposure to fluoride in children and women: A study in a volcanic area.

    Science.gov (United States)

    Linhares, Diana Paula Silva; Garcia, Patrícia Ventura; Amaral, Leslie; Ferreira, Teresa; Cury, Jaime A; Vieira, Waldomiro; Rodrigues, Armindo Dos Santos

    2016-07-01

    The natural enrichment of water with fluoride is related to natural sources such as volcanic activity, with it being documented that fluorosis, an endemic and widespread disease in volcanic areas, is associated to the ingestion of high levels of fluoride through water. Thus, in this study, we aimed to define the fluoride concentration in drinking waters of volcanic origin and compare the sensitivity of urine and nail clippings as biomarkers for fluoride exposure in adults and children. Samples of drinking water from four villages in São Miguel Island (Azores) were used and the fluoride concentration was determined, as well the fluoride content in urine and toenails clippings from 66 children and 63 adults from these villages. A validated diet questionnaire, assessing sources of fluoride, was recorded for each participant. The fluoride determination in urine and nail clipping samples was made using a fluoride-specific electrode. A positive correlation was found between the fluoride daily intake and fluoride content in children urine (rs = 0.475; p < 0.001) and in their nail clippings (rs = 0.475; p < 0.001), while in adult women, the fluoride daily intake correlated positively with fluoride content nail clippings (rs = 0.495, p < 0.001). This reveals that nail clippings are more reliable as biomarkers of chronic exposure to fluoride than urine for populations of different ages (children vs. adults). Furthermore, nail clippings are more suitable than urine fluoride levels to assess long term exposure to fluoride in areas where the exposure to fluoride in drinking water is considered within, or slightly above, the recommended legal values.

  9. Metabolic products as biomarkers

    Science.gov (United States)

    Melancon, M.J.; Alscher, R.; Benson, W.; Kruzynski, G.; Lee, R.F.; Sikka, H.C.; Spies, R.B.; Huggett, Robert J.; Kimerle, Richard A.; Mehrle, Paul M.=; Bergman, Harold L.

    1992-01-01

    Ideally, endogenous biomarkers would indicate both exposure and environmental effects of toxic chemicals; however, such comprehensive biochemical and physiological indices are currently being developed and, at the present time, are unavailable for use in environmental monitoring programs. Continued work is required to validate the use of biochemical and physiological stress indices as useful components of monitoring programs. Of the compounds discussed only phytochelatins and porphyrins are currently in biomarkers in a useful state; however, glutathione,metallothioneins, stress ethylene, and polyamines are promising as biomarkers in environmental monitoring.

  10. 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.

  11. A Validity Study of the Pain Apperception Test

    Science.gov (United States)

    Haase, Richard F.; And Others

    1975-01-01

    This study assessed the validity of the Pain Apperception Test (PAT) against an accepted and validated predictive measure of pain tolerance, a Kinesthetic After Effects Task (KAE). As well, it replicated an earlier finding by Petrovich that suggested that scores derived from the PAT are related significantly to neuroticism. (Author/RK)

  12. Measuring Long-Distance Romantic Relationships: A Validity Study

    Science.gov (United States)

    Pistole, M. Carole; Roberts, Amber

    2011-01-01

    This study investigated aspects of construct validity for the scores of a new long-distance romantic relationship measure. A single-factor structure of the long-distance romantic relationship index emerged, with convergent and discriminant evidence of external validity, high internal consistency reliability, and applied utility of the scores.…

  13. The Self-Consciousness Scale: A Discriminant Validity Study

    Science.gov (United States)

    Carver, Charles S.; Glass, David C.

    1976-01-01

    A validity study is conducted of the Self-Consciousness Scale components with male undergraduates. The components, Private and Public Self Consciousness and Social Anxiety did not correlate with any other measures used to establish their validity and thus seem to be independent of other measures tested. (Author/DEP)

  14. Urinary Sugars--A Biomarker of Total Sugars Intake.

    Science.gov (United States)

    Tasevska, Natasha

    2015-07-01

    Measurement error in self-reported sugars intake may explain the lack of consistency in the epidemiologic evidence on the association between sugars and disease risk. This review describes the development and applications of a biomarker of sugars intake, informs its future use and recommends directions for future research. Recently, 24 h urinary sucrose and fructose were suggested as a predictive biomarker for total sugars intake, based on findings from three highly controlled feeding studies conducted in the United Kingdom. From this work, a calibration equation for the biomarker that provides an unbiased measure of sugars intake was generated that has since been used in two US-based studies with free-living individuals to assess measurement error in dietary self-reports and to develop regression calibration equations that could be used in future diet-disease analyses. Further applications of the biomarker include its use as a surrogate measure of intake in diet-disease association studies. Although this biomarker has great potential and exhibits favorable characteristics, available data come from a few controlled studies with limited sample sizes conducted in the UK. Larger feeding studies conducted in different populations are needed to further explore biomarker characteristics and stability of its biases, compare its performance, and generate a unique, or population-specific biomarker calibration equations to be applied in future studies. A validated sugars biomarker is critical for informed interpretation of sugars-disease association studies.

  15. The Renal Effects of Vanadate Exposure: Potential Biomarkers and Oxidative Stress as a Mechanism of Functional Renal Disorders—Preliminary Studies

    Directory of Open Access Journals (Sweden)

    Agnieszka Ścibior

    2014-01-01

    Full Text Available The alterations in the levels/activities of selected biomarkers for detecting kidney toxicity and in the levels of some oxidative stress (OS markers and elements were studied in male rats to evaluate biochemically the degree of kidney damage, investigate the role of OS in the mechanism of functional renal disorders, reveal potential biomarkers of renal function, and assess the renal mineral changes in the conditions of a 12-week sodium metavanadate (SMV, 0.125 mg V/mL exposure. The results showed that OS is involved in the mechanism underlying the development of SMV-induced functional renal disturbances. They also suggest that the urinary cystatin C (CysCu and kidney injury molecule-1 (KIM-1u could be the most appropriate to evaluate renal function at the conditions of SMV intoxication when the fluid intake, excreted urinary volume (EUV, body weight (BW, and the urinary creatinine excretion (Creu decreased. The use of such tests as the urinary lactate dehydrogenase, alkaline phosphatase, γ-glutamyltranspeptidase, and N-acetyl-β-D-glucosaminidase (LDHu, ALPu, GGTPu, and NAGu seems not to be valid given their reduced activities. The use of only traditional biomarkers of renal function in these conditions may, in turn, be insufficient because their alterations are greatly influenced by the changes in the fluid intake and/or BW.

  16. Validation of biomarkers for distinguishing Mycobacterium tuberculosis from non-tuberculous mycobacteria using gas chromatography-mass spectrometry and chemometrics.

    Directory of Open Access Journals (Sweden)

    Ngoc A Dang

    Full Text Available Tuberculosis (TB remains a major international health problem. Rapid differentiation of Mycobacterium tuberculosis complex (MTB from non-tuberculous mycobacteria (NTM is critical for decisions regarding patient management and choice of therapeutic regimen. Recently we developed a 20-compound model to distinguish between MTB and NTM. It is based on thermally assisted hydrolysis and methylation gas chromatography-mass spectrometry and partial least square discriminant analysis. Here we report the validation of this model with two independent sample sets, one consisting of 39 MTB and 17 NTM isolates from the Netherlands, the other comprising 103 isolates (91 MTB and 12 NTM from Stellenbosch, Cape Town, South Africa. All the MTB strains in the 56 Dutch samples were correctly identified and the model had a sensitivity of 100% and a specificity of 94%. For the South African samples the model had a sensitivity of 88% and specificity of 100%. Based on our model, we have developed a new decision-tree that allows the differentiation of MTB from NTM with 100% accuracy. Encouraged by these findings we will proceed with the development of a simple, rapid, affordable, high-throughput test to identify MTB directly in sputum.

  17. Urinary (1)H Nuclear Magnetic Resonance Metabolomic Fingerprinting Reveals Biomarkers of Pulse Consumption Related to Energy-Metabolism Modulation in a Subcohort from the PREDIMED study.

    Science.gov (United States)

    Madrid-Gambin, Francisco; Llorach, Rafael; Vázquez-Fresno, Rosa; Urpi-Sarda, Mireia; Almanza-Aguilera, Enrique; Garcia-Aloy, Mar; Estruch, Ramon; Corella, Dolores; Andres-Lacueva, Cristina

    2017-04-07

    Little is known about the metabolome fingerprint of pulse consumption. The study of robust and accurate biomarkers for pulse dietary assessment has great value for nutritional epidemiology regarding health benefits and their mechanisms. To characterize the fingerprinting of dietary pulses (chickpeas, lentils, and beans), spot urine samples from a subcohort from the PREDIMED study were stratified using a validated food frequency questionnaire. Urine samples of nonpulse consumers (≤4 g/day of pulse intake) and habitual pulse consumers (≥25 g/day of pulse intake) were analyzed using a (1)H nuclear magnetic resonance (NMR) metabolomics approach combined with multi- and univariate data analysis. Pulse consumption showed differences through 16 metabolites coming from (i) choline metabolism, (ii) protein-related compounds, and (iii) energy metabolism (including lower urinary glucose). Stepwise logistic regression analysis was applied to design a combined model of pulse exposure, which resulted in glutamine, dimethylamine, and 3-methylhistidine. This model was evaluated by a receiver operating characteristic curve (AUC > 90% in both training and validation sets). The application of NMR-based metabolomics to reported pulse exposure highlighted new candidates for biomarkers of pulse consumption and the impact on energy metabolism, generating new hypotheses on energy modulation. Further intervention studies will confirm these findings.

  18. Biomarkers in clinical medicine.

    Science.gov (United States)

    Chen, Xiao-He; Huang, Shuwen; Kerr, David

    2011-01-01

    Biomarkers have been used in clinical medicine for decades. With the rise of genomics and other advances in molecular biology, biomarker studies have entered a whole new era and hold promise for early diagnosis and effective treatment of many diseases. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention (1). They can be classified into five categories based on their application in different disease stages: 1) antecedent biomarkers to identify the risk of developing an illness, 2) screening biomarkers to screen for subclinical disease, 3) diagnostic biomarkers to recognize overt disease, 4) staging biomarkers to categorise disease severity, and 5) prognostic biomarkers to predict future disease course, including recurrence, response to therapy, and monitoring efficacy of therapy (1). Biomarkers can indicate a variety of health or disease characteristics, including the level or type of exposure to an environmental factor, genetic susceptibility, genetic responses to environmental exposures, markers of subclinical or clinical disease, or indicators of response to therapy. This chapter will focus on how these biomarkers have been used in preventive medicine, diagnostics, therapeutics and prognostics, as well as public health and their current status in clinical practice.

  19. Effects of carbofuran on the sea bass (Dicentrarchus labrax L.): study of biomarkers and behaviour alterations.

    Science.gov (United States)

    Hernández-Moreno, David; Pérez-López, Marcos; Soler, Francisco; Gravato, Carlos; Guilhermino, Lúcia

    2011-10-01

    The objective of this study was to investigate the acute effects of the pesticide carbofuran on the sea bass (Dicentrarchus labrax) using parameters at different levels of biological organisation (swimming behaviour and several biomarkers) and possible relationships between alterations found in different effect criteria. In a bioassay, sea bass juveniles were individually exposed to different doses of carbofuran (31, 63, 125 and 250 μg/L) for 96 h. At the end of the bioassay, the swimming performance and 11 biomarkers were determined. Biomarkers were: hepatosomatic index (HSI), lipid peroxidation (LPO), reduced glutathione and the activities of the enzymes ethoxyresorufin O-deethylase (EROD), glutathione S-transferases, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, brain acetylcholinesterase (AChE) and muscle cholinesterases (ChE). After 96 h of exposure, carbofuran induced a decrease of the swimming velocity and inhibition of EROD activity at all concentrations tested, and inhibition of muscle ChE and brain AChE activities at 250 μg/L. No relevant alterations in any of the other tested parameters were found. These results show that carbofuran induced adverse effects on fish by interfering with neurofunction, capability of detoxication and swimming velocity. In addition, positive and significant correlations between the swimming velocity and (i) brain AChE activity, (ii) muscle ChE activity and (iii) EROD activity suggest that the inhibition of these enzymes may somehow be related to the behavioural changes observed. Since these functions are determinant for the survival and performance of the fish in the wild, the findings of the present study suggest that adverse effects may occur in populations exposed to carbofuran if a sufficient number of animals is affected.

  20. Respiratory effects associated with wood fuel use: a cross-sectional biomarker study among adolescents.

    Science.gov (United States)

    Van Miert, Erik; Sardella, Antonia; Nickmilder, Marc; Bernard, Alfred

    2012-04-01

    The use of wood as heating and cooking fuel can result in elevated levels of indoor air pollution, but to what extent this is related to respiratory diseases and allergies is still inconclusive. Here, we report a cross-sectional study among 744 school adolescents (median age 15 years) using as main outcomes respiratory symptoms and diseases, exhaled nitric oxide, total and aeroallergen-specific IgE in serum, and two epithelial biomarkers in nasal lavage fluid (NALF) or serum, that is, Clara cell protein (CC16) and surfactant-associated protein D (SPD). Information about the wood fuel use and potential confounders was collected via a personal interview of the adolescent and a questionnaire filled out by the parents. Two approaches were used to limit the possible influence of confounders, that is, multivariate analysis using the complete study population or pairwise analysis of matched sub-populations obtained using an automated procedure. Wood fuel use was associated with a decrease of CC16 and an increase of SPD in serum, which resulted in a decreased serum CC16/SPD ratio (median -9%, P = 0.001). No consistent differences were observed for the biomarkers measured in exhaled breath or NALF. Wood fuel use was also associated with increased odds for asthma [odds ratio (OR) 2.2, 95% CI: 1.1-4.4, P = 0.02], hay fever (OR = 2.4, 95% CI: 1.4-4.3, P = 0.002), and sensitization against pollen allergens (OR = 2.1, 95% CI: 1.3-3.4, P = 0.002). The risks of respiratory tract infections, self-reported symptoms, and sensitization against house-dust mite were not increased by wood fuel use. The increased risks of asthma, hay fever and aeroallergen sensitization, and the changes of lung-specific biomarkers consistently pointed towards respiratory effects associated with the use of wood fuel.

  1. Blood biomarker for Parkinson disease: peptoids

    Science.gov (United States)

    Yazdani, Umar; Zaman, Sayed; Hynan, Linda S; Brown, L Steven; Dewey, Richard B; Karp, David; German, Dwight C

    2016-01-01

    Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r = 0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker. PMID:27812535

  2. Simulation Based Studies in Software Engineering: A Matter of Validity

    Directory of Open Access Journals (Sweden)

    Breno Bernard Nicolau de França

    2015-04-01

    Full Text Available Despite the possible lack of validity when compared with other science areas, Simulation-Based Studies (SBS in Software Engineering (SE have supported the achievement of some results in the field. However, as it happens with any other sort of experimental study, it is important to identify and deal with threats to validity aiming at increasing their strength and reinforcing results confidence. OBJECTIVE: To identify potential threats to SBS validity in SE and suggest ways to mitigate them. METHOD: To apply qualitative analysis in a dataset resulted from the aggregation of data from a quasi-systematic literature review combined with ad-hoc surveyed information regarding other science areas. RESULTS: The analysis of data extracted from 15 technical papers allowed the identification and classification of 28 different threats to validity concerned with SBS in SE according Cook and Campbell’s categories. Besides, 12 verification and validation procedures applicable to SBS were also analyzed and organized due to their ability to detect these threats to validity. These results were used to make available an improved set of guidelines regarding the planning and reporting of SBS in SE. CONCLUSIONS: Simulation based studies add different threats to validity when compared with traditional studies. They are not well observed and therefore, it is not easy to identify and mitigate all of them without explicit guidance, as the one depicted in this paper.

  3. Biomarkers of environmental benzene exposure

    Energy Technology Data Exchange (ETDEWEB)

    Weisel, C.; Yu, R.; Roy, A.; Georgopoulos, P. [Environmental and Occupational Health Sciences Institute, Piscataway, NJ (United States)

    1996-12-01

    Environmental exposures to benzene result in increases in body burden that are reflected in various biomarkers of exposure, including benzene in exhaled breath, benzene in blood and urinary trans-trans-muconic acid and S-phenylmercapturic acid. A review of the literature indicates that these biomarkers can be used to distinguish populations with different levels of exposure (such as smokers from nonsmokers and occupationally exposed from environmentally exposed populations) and to determine differences in metabolism. Biomarkers in humans have shown that the percentage of benzene metabolized by the ring-opening pathway is greater at environmental exposures than that at higher occupational exposures, a trend similar to that found in animal studies. This suggests that the dose-response curve is nonlinear; that potential different metabolic mechanisms exist at high and low doses; and that the validity of a linear extrapolation of adverse effects measured at high doses to a population exposed to lower, environmental levels of benzene is uncertain. Time-series measurements of the biomarker, exhaled breath, were used to evaluate a physiologically based pharmacokinetic (PBPK) model. Biases were identified between the PBPK model predictions and experimental data that were adequately described using an empirical compartmental model. It is suggested that a mapping of the PBPK model to a compartmental model can be done to optimize the parameters in the PBPK model to provide a future framework for developing a population physiologically based pharmacokinetic model. 44 refs., 3 figs., 1 tab.

  4. Long noncoding RNAs as auxiliary biomarkers for gastric cancer screening: A pooled analysis of individual studies

    Science.gov (United States)

    Cui, Zhaolei; Chen, Yan; Xiao, Zhenzhou; Hu, Minhua; Lin, Yingying; Chen, Yansong; Zheng, Yuhong

    2016-01-01

    Background Long non-coding RNAs (lncRNAs) are highlighted as novel cancer biomarkers with great promise. Herein, we focused on summarizing the overall diagnostic performance of lncRNAs for gastric cancer (GC). Methods Publications fulfilling the search criteria were selected from the online databases. Study quality was assessed according to the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS) checklist. The summary receiver operator characteristic (SROC) curve was plotted using a bivariate meta-analysis model. Statistical analysis was performed based on the platforms of STATA 12.0 and Meta-Disc 1.4 software. Results Fifteen studies with 1252 patients and 1283 matched controls were included. The pooled sensitivity and specificity for lncRNA expression profile in differentiating GC patients from cancer-free individuals were 0.68 (95%CI: 0.61-0.74) and 0.79 (95%CI: 0.72-0.84), respectively, corresponding to an area under curve (AUC) of 0.80. Moreover, the stratified analyses demonstrated that plasma-based lncRNA profiling harbored higher accuracy than that tissue-based assay (specificity: 0.80 versus 0.75; AUC: 0.84 versus 0.77). Conclusions LncRNA profiling hallmarks a moderate diagnostic value in the management of GC and that lncRNA expression patterns may potentially be utilized as auxiliary biomarkers in confirming GC. PMID:27015554

  5. 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.

  6. 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.

  7. Application of proteomics in the discovery of candidate protein biomarkers in a Diabetes Autoantibody Standardization Program sample subset

    Energy Technology Data Exchange (ETDEWEB)

    Metz, Thomas O.; Qian, Weijun; Jacobs, Jon M.; Gritsenko, Marina A.; Moore, Ronald J.; Polpitiya, Ashoka D.; Monroe, Matthew E.; Camp, David G.; mueller, Patricia W.; Smith, Richard D.

    2008-02-01

    Objective. Before biomarkers predictive of type 1 diabetes can be evaluated in proficiency evaluations, they must be identified and validated in initial, exploratory studies. Hypothesis-driven comparative studies may be performed to identify candidate biomarkers but are limited to the current knowledge of metabolic, signaling, and inflammatory pathways in the context of type 1 diabetes. Alternatively, untargeted “-omics” approaches may be employed in profiling studies to identify candidate biomarkers of type 1 diabetes.

  8. Using MALDI-IMS and MRM to stablish a pipeline for discovery and validation of tumor neovasculature biomarker candidates. — EDRN Public Portal

    Science.gov (United States)

    In an effort to circumvent the limitations associated with biomarker discovery workflows involving cell lines and cell cultures, histology-directed MALDI protein profiling and imaging mass spectrometry will be used for identification of vascular endothelial biomarkers suitable for early prostate cancer detection by CEUS targeted molecular imaging

  9. Biomarker-based dissection of neurodegenerative diseases.

    Science.gov (United States)

    Olsson, Bob; Zetterberg, Henrik; Hampel, Harald; Blennow, Kaj

    2011-12-01

    The diagnosis of neurodegenerative diseases within neurology and psychiatry are hampered by the difficulty in getting biopsies and thereby validating the diagnosis by pathological findings. Biomarkers for other types of disease have been readily adopted into the clinical practice where for instance troponins are standard tests when myocardial infarction is suspected. However, the use of biomarkers for neurodegeneration has not been fully incorporated into the clinical routine. With the development of cerebrospinal fluid (CSF) biomarkers that reflect pathological events within the central nervous system (CNS), important clinical diagnostic tools are becoming available. This review summarizes the most promising biomarker candidates that may be used to monitor different types of neurodegeneration and protein inclusions, as well as different types of metabolic changes, in living patients in relation to the clinical phenotype and disease progression over time. Our aim is to provide the reader with an updated lexicon on currently available biomarker candidates, how far they have come in development and how well they reflect pathogenic processes in different neurodegenerative diseases. Biomarkers for specific pathogenetic processes would also be valuable tools both to study disease pathogenesis directly in patients and to identify and monitor the effect of novel treatment strategies.

  10. Studies of biomarkers in aluminum workers occupationally exposed to polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Ovrebø, S; Haugen, A; Hemminki, K; Szyfter, K; Drabløs, P A; Skogland, M

    1995-01-01

    Evaluation of biomarkers for genotoxic exposure are important for future use of such biomarkers in cancer prevention. We have studied a group of aluminum plant workers for a period of 2.5 years. The level of polycyclic aromatic hydrocarbons (PAHs) has been monitored at the work place (cathode relining). During the study period, urine and blood were sampled up to seven times from the same workers. Mean level of urinary 1-hydroxypyrene varied from 1.08 to 2.44 mumol/mol creatinine in the exposed groups compared with 0.36 and 0.20 mumol/mol creatinine in the two reference groups. For a group of 14 workers the intraindividual variation of urinary 1-hydroxypyrene was analyzed. The relative standard deviation of the values was < or = 0.50 for half of the workers; the relative standard deviation was calculated for individual values divided by mean of each time point. Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells from exposed and nonexposed workers were measured by both immunoassay and 32P-postlabeling. By 32P-postlabeling mean values of 12.0 adducts/10(8) and 10.8 adducts/10(8) nucleotides were found in a PAH-exposed group and a reference group, respectively. Intraindividual variation of PAH-DNA adducts was also analyzed.

  11. Retinal vascular caliber is associated with cardiovascular biomarkers of oxidative stress and inflammation: the POLA study.

    Directory of Open Access Journals (Sweden)

    Vincent Daien

    Full Text Available PURPOSE: Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology. PATIENTS AND METHODS: Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3 activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP and orosomucoid. RESULTS: In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (p = 0.003 whereas larger venular caliber was associated with higher levels of hsCRP (p = 0.0001 and orosomucoid (p = 0.01. CONCLUSION: In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology.

  12. The liver toxicity biomarker study phase I: markers for the effects of tolcapone or entacapone.

    Science.gov (United States)

    McBurney, Robert N; Hines, Wade M; VonTungeln, Linda S; Schnackenberg, Laura K; Beger, Richard D; Moland, Carrie L; Han, Tao; Fuscoe, James C; Chang, Ching-Wei; Chen, James J; Su, Zhenqiang; Fan, Xiao-hui; Tong, Weida; Booth, Shelagh A; Balasubramanian, Raji; Courchesne, Paul L; Campbell, Jennifer M; Graber, Armin; Guo, Yu; Juhasz, Peter; Li, Tricia Y; Lynch, Moira D; Morel, Nicole M; Plasterer, Thomas N; Takach, Edward J; Zeng, Chenhui; Beland, Frederick A

    2012-08-01

    The Liver Toxicity Biomarker Study is a systems toxicology approach to discover biomarkers that are indicative of a drug's potential to cause human idiosyncratic drug-induced liver injury. In phase I, the molecular effects in rat liver and blood plasma induced by tolcapone (a "toxic" drug) were compared with the molecular effects in the same tissues by dosing with entacapone (a "clean" drug, similar to tolcapone in chemical structure and primary pharmacological mechanism). Two durations of drug exposure, 3 and 28 days, were employed. Comprehensive molecular analysis of rat liver and plasma samples yielded marker analytes for various drug-vehicle or drug-drug comparisons. An important finding was that the marker analytes associated with tolcapone only partially overlapped with marker analytes associated with entacapone, despite the fact that both drugs have similar chemical structures and the same primary pharmacological mechanism of action. This result indicates that the molecular analyses employed in the study are detecting substantial "off-target" markers for the two drugs. An additional interesting finding was the modest overlap of the marker data sets for 3-day exposure and 28-day exposure, indicating that the molecular changes in liver and plasma caused by short- and long-term drug treatments do not share common characteristics.

  13. Detecting Blood-Based Biomarkers in Metastatic Breast Cancer: A Systematic Review of Their Current Status and Clinical Utility

    Science.gov (United States)

    Berghuis, A. M. Sofie; Koffijberg, Hendrik; Prakash, Jai; Terstappen, Leon W. M. M.; IJzerman, Maarten J.

    2017-01-01

    Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the available evidence of known blood-based biomarkers in metastatic breast cancer, regarding their clinical utility and state-of-the-art position in the validation process. The initial search yielded 1078 original studies, of which 420 were assessed for eligibility. A total of 320 studies were included in the final synthesis. A Development, Evaluation and Application Chart (DEAC) of all biomarkers was developed. Most studies focus on identifying new biomarkers and search for relations between these biomarkers and traditional molecular characteristics. Biomarkers are usually investigated in only one study (68.8%). Only 9.8% of all biomarkers was investigated in more than five studies. Circulating tumor cells, gene expression within tumor cells and the concentration of secreted proteins are the most frequently investigated biomarkers in liquid biopsies. However, there is a lack of studies focusing on identifying the clinical utility of these biomarkers, by which the additional value still seems to be limited according to the investigated evidence. PMID:28208771

  14. Human Rights Attitude Scale: A Validity and Reliability Study

    Science.gov (United States)

    Ercan, Recep; Yaman, Tugba; Demir, Selcuk Besir

    2015-01-01

    The objective of this study is to develop a valid and reliable attitude scale having quality psychometric features that can measure secondary school students' attitudes towards human rights. The study group of the research is comprised by 710 6th, 7th and 8th grade students who study at 4 secondary schools in the centre of Sivas. The study group…

  15. 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.

  16. A multicenter photoprovocation study to identify potential biomarkers by global peptide profiling in cutaneous lupus erythematosus.

    Science.gov (United States)

    Calderon, C; Zucht, H D; Kuhn, A; Wozniacka, A; Szepietowski, J C; Nyberg, F; Weichenthal, M; Piantone, A; Budde, P

    2015-11-01

    Cutaneous lupus erythematosus (CLE) is an inflammatory autoimmune skin disease in which abnormal photosensitivity is an important pathogenetic factor but is difficult to predict, creating a challenge in determining treatment efficacy. Although photosensitivity in CLE patients may change over time, photoprovocation testing with ultraviolet (UV) A and UVB irradiation can be a helpful tool to explore differences between responders and nonresponders during photoprovocation. To identify biomarkers that could substitute for the clinical endpoint lesion development, we performed a global peptidomics profiling analysis of CLE subjects in a controlled photoprovocation study. Plasma and skin biopsy samples were collected before and after UV-irradiation from 13 healthy volunteers and 47 CLE subjects. Twenty-two of the 47 CLE subjects developed skin lesions. The samples were analyzed using a label-free quantitative peptidomics workflow combined with univariate and multivariate statistical analyses. The primary finding was identification of a specific plasma peptide signature separating responders versus nonresponders at baseline. The peptide signature consisted of beta 2-microglobulin (B2MG), human beta-defensin-1, and peptides derived from CD99, polymeric immunoglobulin receptor, and immunoglobulin kappa light chains. In skin, elevated B2MG levels correlated with lesion formation. Our results show that the peptidome is a rich source of potential biomarkers for predicting photosensitivity in CLE.

  17. 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.

  18. Validation of an asthma symptom diary for interventional studies

    OpenAIRE

    Santanello, N.; Davies, G.(Imperial College, London, UK); Galant, S.; Pedinoff, A.; Sveum, R.; Seltzer, J.; Seidenberg, B.; Knorr, B.

    1999-01-01

    OBJECTIVE—The Pediatric Asthma Diary was developed and validated to assess efficacy of interventions in children with asthma.
DESIGN, PATIENTS, AND SETTING—Diary validation was performed in a three week, prospective study of 106 children aged 6-14 years with asthma. Children were classified at baseline as either stable (requiring no additional asthma treatment) or new onset/worse (requiring either addition of or increase in anti-inflammatory treatment).
RESULTS—A dayti...

  19. Cerebrovascular reactivity by quantitative magnetic resonance angiography with a co{sub 2} challenge. Validation as a new imaging biomarker

    Energy Technology Data Exchange (ETDEWEB)

    Caputi, Luigi, E-mail: lcaputi@istituto-besta.it [Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milan (Italy); Ghielmetti, Francesco, E-mail: Francesco.Ghielmetti@istituto-besta.it [Department of Neuroradiology, Fondazione IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milan (Italy); Faragò, Giuseppe, E-mail: Giuseppe.Farago@istituto-besta.it [Department of Neuroradiology, Fondazione IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milan (Italy); Longaretti, Fabio, E-mail: fabio.longaretti@libero.it [Department of Neuroradiology, Fondazione IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milan (Italy); Lamperti, Massimo, E-mail: docmassimomd@gmail.com [Department of Neuroanesthesia and Intensive Care, Fondazione IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milan (Italy); Anzola, Gian Paolo, E-mail: gpanzola@speedyposta.it [Service of Neurology, S. Orsola Hospital, Fondazione Poliambulanza, Via Vittorio Emanuele II 27, 25122 Brescia (Italy); Carriero, Maria Rita, E-mail: MariaRita.Carriero@istituto-besta.it [Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milan (Italy); Charbel, Fady T., E-mail: fcharbel@uic.edu [Department of Neurosurgery, University of Illinois at Chicago College of Medicine, Chicago, IL 60612 (United States); Bruzzone, Maria Grazia, E-mail: Maria.Bruzzone@istituto-besta.it [Department of Neuroradiology, Fondazione IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milan (Italy); Parati, Eugenio, E-mail: Eugenio.Parati@istituto-besta.it [Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milan (Italy); Ciceri, Elisa, E-mail: Elisa.Ciceri@istituto-besta.it [Department of Neuroradiology, Fondazione IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milan (Italy)

    2014-06-15

    Assessment of cerebrovascular reactivity (CVR) is essential in cerebrovascular diseases, as exhausted CVR may enhance the risk of cerebral ischemic events. Transcranial Doppler (TCD) with a vasodilatory stimulus is currently used for CVR evaluation. Scanty data are available for Quantitative Magnetic Resonance Angiography (QMRA), which supplies higher spatial resolution and quantitative cerebral blood flow values. Aims of our pilot study were: (a) to assess safety and feasibility of CO{sub 2} administration during QMRA, (b) evaluation of CVR under QMRA compared to TCD, and (c) quantitative evaluation of blood flow from the major intracranial arterial vessels both at rest and after CO{sub 2}. CVR during 5% CO{sub 2} air breathing was measured with TCD as a reference method and compared with QMRA. Fifteen healthy subjects (age 60.47 ± 2.24; male 11/15) were evaluated at rest and during CO{sub 2} challenge. Feasibility and safety of QMRA under CO{sub 2} were ensured in all subjects. CVR from middle cerebral artery territory was not statistically different between TCD and MRI (p > 0.05). Mean arterial pressure (MAP) and heart rate (HR) increased during QMRA and TCD (MAP p = 0.007 and p = 0.001; HR p = 0.043 and p = 0.068, respectively). Blood flow values from all intracranial vessels increased after CO{sub 2} inhalation (p < 0.001). CO{sub 2} administration during QMRA sessions is safe and feasible. Good correlation in terms of CVR was obtained comparing TCD and QMRA. Blood flow values significantly increased from all intracranial arterial vessels after CO{sub 2}. Studies regarding CVR in physiopathological conditions might consider the utilization of QMRA both in routine clinical settings and in research projects.

  20. 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...... 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.......-up of a population-based intervention study, The Inter99 Study (1999-2006, Copenhagen, Denmark). A group of 6536 men and women, aged 35-65, was invited to attend a health examination and fill in a self-report questionnaire. Multiple linear regression analysis was applied. Results: Response rate was 69% (N = 4511...

  1. Far Beyond the Usual Biomarkers in Breast Cancer: A Review

    Science.gov (United States)

    dos Anjos Pultz, Brunna; da Luz, Felipe Andrés Cordero; de Faria, Paulo Rogério; Oliveira, Ana Paula Lima; de Araújo, Rogério Agenor; Silva, Marcelo José Barbosa

    2014-01-01

    Research investigating biomarkers for early detection, prognosis and the prediction of treatment responses in breast cancer is rapidly expanding. However, no validated biomarker currently exists for use in routine clinical practice, and breast cancer detection and management remains dependent on invasive procedures. Histological examination remains the standard for diagnosis, whereas immunohistochemical and genetic tests are utilized for treatment decisions and prognosis determinations. Therefore, we conducted a comprehensive review of literature published in PubMed on breast cancer biomarkers between 2009 and 2013. The keywords that were used together were breast cancer, biomarkers, diagnosis, prognosis and drug response. The cited references of the manuscripts included in this review were also screened. We have comprehensively summarized the performance of several biomarkers for diagnosis, prognosis and predicted drug responses of breast cancer. Finally, we have identified 15 biomarkers that have demonstrated promise in initial studies and several miRNAs. At this point, such biomarkers must be rigorously validated in the clinical setting to be translated into clinically useful tests for the diagnosis, prognosis and prediction of drug responses of breast cancer. PMID:25057307

  2. Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!

    Science.gov (United States)

    Pinho, Rosa T.; Waghabi, Mariana C.; Cardillo, Fabíola; Mengel, José; Antas, Paulo R. Z.

    2016-01-01

    Biomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management-related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials. PMID:27563302

  3. 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.

  4. Emphatic Tendency Scale for Student Teachers: Validity and Reliability Studies

    Science.gov (United States)

    Kocak, Canan; Onen, Aysem Seda

    2013-01-01

    The purpose of this study was to analyze the validity and reliability of the Empathic Tendency Scale, which was developed in order to identify student teachers' empathic tendencies. The sampling of the study consisted of 730 student teachers studying at Hacettepe University Faculty of Education. To determine the factor pattern of Empathic…

  5. Identification of valid reference genes for microRNA expression studies in a hepatitis B virus replicating liver cell line

    DEFF Research Database (Denmark)

    Jacobsen, Kari Stougaard; Nielsen, Kirstine Overgaard; Nordmann Winther, Thilde;

    2016-01-01

    BACKGROUND: MicroRNAs are regulatory molecules and suggested as non-invasive biomarkers for molecular diagnostics and prognostics. Altered expression levels of specific microRNAs are associated with hepatitis B virus infection and hepatocellular carcinoma. We previously identified differentially...... of hepatitis B virus expression vectors. RT-qPCR is the preferred method for microRNA studies, and a careful normalisation strategy, verifying the optimal set of reference genes, is decisive for correctly evaluating microRNA expression levels. The aim of this study was to provide valid reference genes...... identified miR-24-3p, miR-151a-5p, and miR-425-5p as the most valid combination of reference genes for microRNA RT-qPCR studies in our hepatitis B virus replicating HepG2 cell model....

  6. Cohort Profile: The Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan.

    Science.gov (United States)

    Cornman, Jennifer C; Glei, Dana A; Goldman, Noreen; Chang, Ming-Cheng; Lin, Hui-Sheng; Chuang, Yi-Li; Hurng, Baai-Shyun; Lin, Yu-Hsuan; Lin, Shu-Hui; Liu, I-Wen; Liu, Hsia-Yuan; Weinstein, Maxine

    2016-02-01

    The Social Environment and Biomarkers of Aging Study (SEBAS) is a nationally representative longitudinal survey of Taiwanese middle-aged and older adults. It adds the collection of biomarkers and performance assessments to the Taiwan Longitudinal Study of Aging (TLSA), a nationally representative study of adults aged 60 and over, including the institutionalized population. The TLSA began in 1989, with follow-ups approximately every 3 years; younger refresher cohorts were added in 1996 and 2003. The first wave of SEBAS, based on a sub-sample of respondents from the 1999 TLSA, was conducted in 2000. A total of 1023 respondents completed both a face-to-face home interview and, several weeks later, a hospital-based physical examination. In addition to a 12-h (7 pm-7 am) urine specimen collected the night before and a fasting blood specimen collected during the examination, trained staff measured blood pressure, height, weight and waist and hip circumferences. A second wave of SEBAS was conducted in 2006 using a similar protocol to SEBAS 2000, but with the addition of performance assessments conducted by the interviewers at the end of the home interview. Both waves of SEBAS also included measures of health status (physical, emotional, cognitive), health behaviours, social relationships and exposure to stressors. The SEBAS data, which are publicly available at [http://www.icpsr.umich.edu/icpsrweb/NACDA/studies/3792/version/5], allow researchers to explore the relationships among life challenges, the social environment and health and to examine the antecedents, correlates and consequences of change in biological measures and health.

  7. Fish metalloproteins as biomarkers of environmental contamination.

    Science.gov (United States)

    Hauser-Davis, Rachel Ann; de Campos, Reinaldo Calixto; Ziolli, Roberta Lourenço

    2012-01-01

    Fish are well-recognized bioindicators of environmental contamination. Several recent proteomic studies have demonstrated the validity and value of using fish in the search and discovery of new biomarkers. Certain analytical tools, such as comparative protein expression analyses, both in field and lab exposure studies, have been used to improve the understanding of the potential for chemical pollutants to cause harmful effects. The metallomic approach is in its early stages of development, but has already shown great potential for use in ecological and environmental monitoring contexts. Besides discovering new metalloproteins that may be used as biomarkers for environmental contamination, metallomics can be used to more comprehensively elucidate existing biomarkers, which may enhance their effectiveness. Unfortunately, metallomic profiling for fish has not been explored, because only a few fish metalloproteins have thus far been discovered and studied. Of those that have, some have shown ecological importance, and are now successfully used as biomarkers of environmental contamination. These biomarkers have been shown to respond to several types of environmental contamination, such as cyanotoxins, metals, and sewage effluents, although many do not yet possess any known function. Examples of successes include MMPs, superoxide dismutases, selenoproteins, and iron-bound proteins. Unfortunately, none of these have, as yet, been extensively studied. As data are developed for them, valuable new information on their roles in fish physiology and in inducing environmental effects should become available.

  8. Implementation of proteomic biomarkers: making it work

    Science.gov (United States)

    Mischak, Harald; Ioannidis, John PA; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia

    2012-01-01

    While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. PMID:22519700

  9. Independent Candidate Serum Protein Biomarkers of Response to Adalimumab and to Infliximab in Rheumatoid Arthritis: An Exploratory Study.

    Directory of Open Access Journals (Sweden)

    Ignacio Ortea

    Full Text Available Response to treatment of rheumatoid arthritis shows large inter-individual variability. This heterogeneity is observed with all the anti-rheumatic drugs, including the commonly used TNF inhibitors. It seems that drug-specific and target-specific factors lead individual patients to respond or not to a given drug, although this point has been challenged. The search of biomarkers distinguishing responders from non-responders has included shotgun proteomics of serum, as a previous study of response to infliximab, an anti-TNF antibody. Here, we have used the same study design and technology to search biomarkers of response to a different anti-TNF antibody, adalimumab, and we have compared the results obtained for the two anti-TNF drugs. Search of biomarkers of response to adalimumab included depletion of the most abundant serum proteins, 8-plex isobaric tag for relative and absolute quantitation (iTRAQ labeling, two-dimensional liquid chromatography fractionation and relative quantification with a hybrid Orbitrap mass spectrometer. With this approach, 264 proteins were identified in all the samples with at least 2 peptides and 95% confidence. Nine proteins showed differences between non-responders and responders (P < 0.05, representing putative biomarkers of response to adalimumab. These results were compared with the previous study of infliximab. Surprisingly, the non-responder/responder differences in the two studies were not correlated (rs = 0.07; P = 0.40. This overall independence with all the proteins showed two identifiable components. On one side, the putative biomarkers of response to either adalimumab or infliximab, which were not shared and showed an inverse correlation (rs = -0.69; P = 0.0023. On the other, eight proteins showing significant non-responder/responder differences in the analysis combining data of response to the two drugs. These results identify new putative biomarkers of response to treatment of rheumatoid arthritis and

  10. 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...

  11. 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.

  12. 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, thir

  13. California Diploma Project Technical Report III: Validity Study--Validity Study of the Health Sciences and Medical Technology Standards

    Science.gov (United States)

    McGaughy, Charis; Bryck, Rick; de Gonzalez, Alicia

    2012-01-01

    This study is a validity study of the recently revised version of the Health Science Standards. The purpose of this study is to understand how the Health Science Standards relate to college and career readiness, as represented by survey ratings submitted by entry-level college instructors of health science courses and industry representatives. For…

  14. Imagery Measures of Ego, Id, Superego, and Identity: Validity Studies.

    Science.gov (United States)

    Cartwright, D.; DeBruin, J.

    1988-01-01

    Five validity studies of the id, ego, superego, and identity scales of the Study of Imagery are reported, using undergraduate students. Multistage Bonferroni procedures are used to evaluate the significance of results. The scales are related to each other and to toughmindedness, self-control, and behavioral conflict. (TJH)

  15. A Re-analysis of Published Differential Validity Studies.

    Science.gov (United States)

    Ruch, William W.

    A survey of recent literature was undertaken to locate validity studies of paper-and-pencil tests which met the following criteria: (1) Studies were conducted in a business or industrial (i.e. non-education, non-military) setting; (2) Separate statistics were available for blacks and whites; (3) Race was not confounded with some outside variable…

  16. The Jackson Career Explorer: Two Further Validity Studies

    Science.gov (United States)

    Schermer, Julie Aitken

    2012-01-01

    The present report consists of two further validity studies using the Jackson Career Explorer (JCE), a short form and continuous version of the Jackson Vocational Interest Survey, measuring 34 interests. The first study examined the relationships between the JCE and five personality factors, from a sample of 528 individuals. The correlations found…

  17. Diagnostic cerebrospinal fluid biomarkers for Parkinson's disease: a pathogenetically based approach.

    Science.gov (United States)

    van Dijk, Karin D; Teunissen, Charlotte E; Drukarch, Benjamin; Jimenez, Connie R; Groenewegen, Henk J; Berendse, Henk W; van de Berg, Wilma D J

    2010-09-01

    The inaccuracy of the early diagnosis of Parkinson's disease (PD) has been a major incentive for studies aimed at the identification of biomarkers. Brain-derived cerebrospinal fluid (CSF) proteins are potential biomarkers considering the major role that proteins play in PD pathogenesis. In this review, we discuss the current hypotheses about the pathogenesis of PD and identify the most promising candidate biomarkers among the CSF proteins studied so far. The list of potential markers includes proteins involved in various pathogenetic processes, such as oxidative stress and protein aggregation. This list will undoubtedly grow in the near future by application of CSF proteomics and subsequent validation of identified proteins. Probably a single biomarker will not suffice to reach high sensitivity and specificity, because PD is pathogenetically heterogeneous and shares etiological factors with other neurodegenerative diseases. Furthermore, identified candidate biomarkers will have to be thoroughly validated before they can be implemented as diagnostic aids.

  18. Measurement and modeling of exposure to selected air toxics for health effects studies and verification by biomarkers.

    Science.gov (United States)

    Harrison, Roy M; Delgado-Saborit, Juana Maria; Baker, Stephen J; Aquilina, Noel; Meddings, Claire; Harrad, Stuart; Matthews, Ian; Vardoulakis, Sotiris; Anderson, H Ross

    2009-06-01

    with the adsorbent resins Tenax GR and Carbotrap, and separate tubes for the collection of 1,3-butadiene were packed with Carbopack B and Carbosieve S-III. After sampling, the tubes were analyzed by means of a thermal desorber interfaced with a gas chromatograph-mass spectrometer (GC-MS). Particle-phase PAHs collected onto a quartz-fiber filter were extracted with solvent, purified, and concentrated before being analyzed with a GC-MS. Urinary biomarkers were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Both the environmental concentrations and personal exposure concentrations measured in this study are lower than those in the majority of earlier published work, which is consistent with the reported application of abatement measures to the control of air toxics emissions. The environmental concentration data clearly demonstrate the influence of traffic sources and meteorologic conditions leading to higher air toxics concentrations in the winter and during peak-traffic hours. The seasonal effect was also observed in indoor environments, where indoor sources add to the effects of the previously identified outdoor sources. The variability of personal exposure concentrations of VOCs and PAHs mainly reflects the range of activities the subjects engaged in during the five-day period of sampling. A number of generic factors have been identified to influence personal exposure concentrations to VOCs, such as the presence of an integral garage (attached to the home), exposure to environmental tobacco smoke (ETS), use of solvents, and commuting. In the case of the medium- and high-molecular-weight PAHs, traffic and ETS are important contributions to personal exposure. Personal exposure concentrations generally exceed home indoor concentrations, which in turn exceed outdoor concentrations. The home microenvironment is the dominant individual contributor to personal exposure. However, for those subjects with particularly high personal exposures, activities

  19. Phrenic nerve conduction studies as a biomarker of respiratory insufficiency in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Jenkins, J A Liberty; Sakamuri, Sarada; Katz, Jonathan S; Forshew, Dallas A; Guion, Lee; Moore, Dan; Miller, Robert G

    2016-01-01

    Our objective was to examine the value of phrenic nerve conduction studies (PNCS) in quantifying diaphragm dysfunction in ALS, as no ideal test of respiratory insufficiency exists in ALS. We prospectively recorded bilateral PNCS, forced vital capacity (FVC), maximum inspiratory pressure (MIP), sniff nasal inspiratory pressure (SNIP), respiratory rate, ALSFRS-R, and respiratory symptoms in 100 ALS patients attending our clinic over a nine-month period. Survival data were collected for two years. Results showed that PNCS were reproducible and well tolerated. When the Pamp was abnormal (respiratory rate >18 was 7.2 (95% CI 2.2-37.2, p 80%. The median survival was 1.07 years when the Pamp was 2 years when the Pamp was >0.3 mV (p respiratory insufficiency and may prove to be a useful biomarker of respiratory dysfunction in ALS.

  20. Potential Biomarkers of Fat Loss as a Feature of Cancer Cachexia

    Directory of Open Access Journals (Sweden)

    Maryam Ebadi

    2015-01-01

    Full Text Available Fat loss is associated with shorter survival and reduced quality of life in cancer patients. Effective intervention for fat loss in cachexia requires identification of the condition using prognostic biomarkers for early detection and prevention of further depletion. No biomarkers of fat mass alterations have been defined for application to the neoplastic state. Several inflammatory cytokines have been implicated in mediating fat loss associated with cachexia; however, plasma levels may not relate to adipose atrophy. Zinc-α2-glycoprotein may be a local catabolic mediator within adipose tissue rather than serving as a plasma biomarker of fat loss. Plasma glycerol and leptin associate with adipose tissue atrophy and mass, respectively; however, no study has evaluated their potential as a prognostic biomarker of cachexia-associated fat loss. This review confirms the need for further studies to identify valid prognostic biomarkers to identify loss of fat based on changes in plasma levels of biomarkers.

  1. 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.

  2. Development of Parkinson's disease biomarkers.

    Science.gov (United States)

    Prakash, Kumar M; Tan, Eng-King

    2010-12-01

    Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting over 6 million people worldwide. It is anticipated that the number of affected individuals may increase significantly in the most populous nations by 2030. During the past 20 years, much progress has been made in identifying and assessing various potential clinical, biochemical, imaging and genetic biomarkers for PD. Despite the wealth of information, development of a validated biomarker for PD is still ongoing. It is hoped that reliable and well-validated biomarkers will provide critical clues to assist in the diagnosis and management of Parkinson's disease patients in the near future.

  3. 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

  4. IDBD: infectious disease biomarker database.

    Science.gov (United States)

    Yang, In Seok; Ryu, Chunsun; Cho, Ki Joon; Kim, Jin Kwang; Ong, Swee Hoe; Mitchell, Wayne P; Kim, Bong Su; Oh, Hee-Bok; Kim, Kyung Hyun

    2008-01-01

    Biomarkers enable early diagnosis, guide molecularly targeted therapy and monitor the activity and therapeutic responses across a variety of diseases. Despite intensified interest and research, however, the overall rate of development of novel biomarkers has been falling. Moreover, no solution is yet available that efficiently retrieves and processes biomarker information pertaining to infectious diseases. Infectious Disease Biomarker Database (IDBD) is one of the first efforts to build an easily accessible and comprehensive literature-derived database covering known infectious disease biomarkers. IDBD is a community annotation database, utilizing collaborative Web 2.0 features, providing a convenient user interface to input and revise data online. It allows users to link infectious diseases or pathogens to protein, gene or carbohydrate biomarkers through the use of search tools. It supports various types of data searches and application tools to analyze sequence and structure features of potential and validated biomarkers. Currently, IDBD integrates 611 biomarkers for 66 infectious diseases and 70 pathogens. It is publicly accessible at http://biomarker.cdc.go.kr and http://biomarker.korea.ac.kr.

  5. Genome-wide association study for biomarker identification of Rapamycin and Everolimus using a lymphoblastoid cell line system

    Directory of Open Access Journals (Sweden)

    Jing eJiang

    2013-08-01

    Full Text Available The mammalian target of rapamycin (mTOR inhibitors, a set of promising potential anti-cancer agents, has shown response variability among individuals. This study aimed to identify novel biomarkers and mechanisms that might influence the response to Rapamycin and Everolimus. Genome-wide association (GWA analyses involving single nucleotide polymorphisms (SNPs, mRNA and microRNAs microarray data were assessed for association with area under the cytotoxicity dose response curve (AUC of two mTOR inhibitors in 272 human lymphoblastoid cell lines (LCLs. Integrated analysis among SNPs, expression data, microRNA data and AUC values were also performed to help select candidate genes for further functional characterization. Functional validation of candidate genes using siRNA screening in multiple cell lines followed by MTS assays for the two mTOR inhibitors were performed. We found that 16 expression probe sets (genes that overlapped between the two drugs were associated with AUC values of two mTOR inhibitors. 127 and 100 SNPs had P<10-4, while 8 and 10 SNPs had P<10-5 with Rapamycin and Everolimus AUC, respectively. Functional studies indicated that 13 genes significantly altered cell sensitivity to either one or both drugs in at least one cell line. Additionally, one microRNA, miR-10a, was significantly associated with AUC values for both drugs and was shown to repress expression of genes that were associated with AUC and desensitize cells to both drugs. In summary, this study identified genes and a microRNA that might contribute to response to mTOR inhibitors.

  6. Testing of the preliminary OMERACT validation criteria for a biomarker to be regarded as reflecting structural damage endpoints in rheumatoid arthritis clinical trials: the example of C-reactive protein

    DEFF Research Database (Denmark)

    Keeling, Stephanie O; Landewe, Robert; van der Heijde, Desiree;

    2007-01-01

    OBJECTIVE: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker...... of individual criteria in the draft set. METHODS: A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants......-based survey. RESULTS: Minimal data were extracted from the literature pertaining to those criteria listed under the category of truth. Ratings for strength of evidence were moderate to low (

  7. 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 concentr

  8. Microphytobenthos biomass and community composition studied by pigment biomarkers: importance and fate in the carbon cycle of a tidal flat

    NARCIS (Netherlands)

    Barranguet, C.; Herman, P.M.J.; Sinke, J.J.

    1997-01-01

    Microphytobenthos biomass and community composition vi ere studied by the use of pigment biomarkers during one year at a tidal flat located in the Westerschelde (SW Netherlands). Benthic microphytes appeared to be an important carbon source in the Westerschelde, especially in the central part of the

  9. Prediction of fruit and vegatable intake from biomarkers using individual participant data of diet-controntrolled intervantion studies

    NARCIS (Netherlands)

    Souverein, O.W.; Vries, de J.H.M.; Winkels, R.M.; 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 (a-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C concentr

  10. Biomarker-based prediction of inflammatory bowel disease-related colorectal cancer: a case–control study

    NARCIS (Netherlands)

    M.M. Gerrits (Monique); M. Chen (Min); J.J.M. Theeuwes (Myrte); H. van Dekken (Herman); M. Sikkema (Marjolein); E.W. Steyerberg (Ewout); H.F. Lingsma (Hester); P.D. Siersema (Peter); B. Xia (Bing); J.G. Kusters (Johannes); C.J. van der Woude (Janneke); E.J. Kuipers (Ernst)

    2011-01-01

    textabstractRegular colonoscopic surveillance for detection of dysplasia is recommended in longstanding inflammatory bowel disease (IBD), however, its sensitivity is disputed. Screening accuracy may increase by using a biomarker-based surveillance strategy.A case-control study was performed to deter

  11. A prospective cohort study of biomarkers of prenatal tobacco smoke exposure: the correlation between serum and meconium and their association with infant birth weight

    Directory of Open Access Journals (Sweden)

    Braun Joe M

    2010-08-01

    Full Text Available Abstract Background The evaluation of infant meconium as a cumulative matrix of prenatal toxicant exposure requires comparison to established biomarkers of prenatal exposure. Methods We calculated the frequency of detection and concentration of tobacco smoke metabolites measured in meconium (nicotine, cotinine, and trans-3'-hydroxycotinine concentrations and three serial serum cotinine concentrations taken during the latter two-thirds of pregnancy among 337 mother-infant dyads. We estimated the duration and intensity of prenatal tobacco smoke exposure using serial serum cotinine concentrations and calculated geometric mean meconium tobacco smoke metabolite concentrations according to prenatal exposure. We also compared the estimated associations between these prenatal biomarkers and infant birth weight using linear regression. Results We detected nicotine (80%, cotinine (69%, and trans-3'-hydroxycotinine (57% in most meconium samples. Meconium tobacco smoke metabolite concentrations were positively associated with serum cotinine concentrations and increased with the number of serum cotinine measurements consistent with secondhand or active tobacco smoke exposure. Like serum cotinine, meconium tobacco smoke metabolites were inversely associated with birth weight. Conclusions Meconium is a useful biological matrix for measuring prenatal tobacco smoke exposure and could be used in epidemiological studies that enroll women and infants at birth. Meconium holds promise as a biological matrix for measuring the intensity and duration of environmental toxicant exposure and future studies should validate the utility of meconium using other environmental toxicants.

  12. Alkoxyresorufin-O-deethylase activities and polychlorinated biphenyl patterns in shrews as biomarkers in environmental risk assessments: sensitivity and specificity

    NARCIS (Netherlands)

    Brink, van den N.W.; Bosveld, A.T.C.

    2005-01-01

    Alkoxyresorufin-O-deethylase (AROD) biomarkers are useful indicators of the exposure of organisms to dioxin-like compounds. In the current study, an in vivo validation of the use of such biomarkers in shrews was conducted. Furthermore, the use of changes in polychlorinated biphenyl (PCB) patterns as

  13. Instruments for the assessment of social anxiety disorder: Validation studies.

    Science.gov (United States)

    Osório, Flávia de Lima; Crippa, José Alexandre de Souza; Loureiro, Sonia Regina

    2012-10-22

    Great progress has been observed in the literature over the last decade regarding the validation of instruments for the assessment of Social Anxiety Disorder in the Brazilian context. Particularly outstanding in this respect is the production of a group of Brazilian investigators regarding the psychometric study of the following instruments: Liebowitz Social Anxiety Scale, Social Phobia Inventory, Brief Social Phobia Scale, Disability Profile, Liebowitz Self-Rated Disability Scale, Social Phobia Safety Behaviors Scale and Self-Statements During Public Speaking Scale, which have proved to be appropriate and valid for use in the adult Brazilian population, representing resources for the assessment of social anxiety in clinical and experimental situations.

  14. A validation study of the Brief Irrational Thoughts Inventory

    NARCIS (Netherlands)

    L.M. Hoogsteder; I.B. Wissink; G.J.J.M. Stams; J.E. van Horn; J. Hendriks

    2014-01-01

    This study examines the reliability and validity of the "Brief Irrational Thoughts Inventory" (BITI) in a sample of 256 justice-involved youths. The BITI is a questionnaire used to determine the nature and severity of irrational thoughts related to aggressive (externalizing), sub-assertive (internal

  15. Model validation studies of solar systems, Phase III. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Lantz, L.J.; Winn, C.B.

    1978-12-01

    Results obtained from a validation study of the TRNSYS, SIMSHAC, and SOLCOST solar system simulation and design are presented. Also included are comparisons between the FCHART and SOLCOST solar system design programs and some changes that were made to the SOLCOST program. Finally, results obtained from the analysis of several solar radiation models are presented. Separate abstracts were prepared for ten papers.

  16. Understanding Foreign Language Learning Strategies: A Validation Study

    Science.gov (United States)

    Tragant, Elsa; Thompson, Marilyn S.; Victori, Mia

    2013-01-01

    The present work aims to contribute to our understanding of the underlying dimensions of language learning strategies in foreign language contexts. The study analyzes alternative factor structures underlying a recently developed instrument (Tragant and Victori, 2012) and it includes the age factor in the examination of its construct validity. The…

  17. A Validity Study of the Self-Esteem Inventory.

    Science.gov (United States)

    Landis, H. John

    Results of this validation study of a slightly modified version of the Coppersmith Self-Esteem Inventory substantiate its use with seventh graders to assess Goal I (concerning self-understanding and appreciation of self-worth) of the Educational Quality Assessment Program in Pennsylvania. Appendixes include the definition and rationale for Goal I,…

  18. Teachers' Engagement at Work: An International Validation Study

    Science.gov (United States)

    Klassen, Robert M.; Aldhafri, Said; Mansfield, Caroline F.; Purwanto, Edy; Siu, Angela F. Y.; Wong, Marina W.; Woods-McConney, Amanda

    2012-01-01

    This study explored the validity of the Utrecht Work Engagement Scale in a sample of 853 practicing teachers from Australia, Canada, China (Hong Kong), Indonesia, and Oman. The authors used multigroup confirmatory factor analysis to test the factor structure and measurement invariance across settings, after which they examined the relationships…

  19. Rap-Music Attitude and Perception Scale: A Validation Study

    Science.gov (United States)

    Tyson, Edgar H.

    2006-01-01

    Objective: This study tests the validity of the Rap-music Attitude and Perception (RAP) Scale, a 1-page, 24-item measure of a person's thoughts and feelings surrounding the effects and content of rap music. The RAP was designed as a rapid assessment instrument for youth programs and practitioners using rap music and hip hop culture in their work…

  20. 29 CFR 1607.5 - General standards for validity studies.

    Science.gov (United States)

    2010-07-01

    ... ability learned in brief orientation period. In general, users should avoid making employment decisions on... orientation period, and which have an adverse impact. G. Method of use of selection procedures. The evidence... market and the job should be considered in the determination of when a validity study is outdated....

  1. A Validation Study of Maslow's Hierarchy of Needs Theory.

    Science.gov (United States)

    Clay, Rex J.

    A study was conducted to expand the body of research that tests the validity of Abraham Maslow's hierarchy of needs theory in a work context where it often serves as a guide for the supervisor's relationships with his subordinates. Data was gathered by questionnaire which tested for a hierarchy of needs among instructors at four community colleges…

  2. A Validation Study of the Student Oral Proficiency Assessment (SOPA).

    Science.gov (United States)

    Thompson, Lynn E.; Kenyon, Dorry M.; Rhodes, Nancy C.

    This study validated the Student Oral Proficiency Assessment (SOPA), an oral proficiency instrument designed for students in elementary foreign language programs. Elementary students who were tested with the SOPA were also administered other instruments designed to measure proficiency. These instruments included the Stanford Foreign Language Oral…

  3. Evaluation of different biomarkers to predict individual radiosensitivity in an inter-laboratory comparison--lessons for future studies.

    Directory of Open Access Journals (Sweden)

    Burkhard Greve

    Full Text Available Radiotherapy is a powerful cure for several types of solid tumours, but its application is often limited because of severe side effects in individual patients. With the aim to find biomarkers capable of predicting normal tissue side reactions we analysed the radiation responses of cells from individual head and neck tumour and breast cancer patients of different clinical radiosensitivity in a multicentric study. Multiple parameters of cellular radiosensitivity were analysed in coded samples of peripheral blood lymphocytes (PBLs and derived lymphoblastoid cell lines (LCLs from 15 clinical radio-hypersensitive tumour patients and compared to age- and sex-matched non-radiosensitive patient controls and 15 lymphoblastoid cell lines from age- and sex- matched healthy controls of the KORA study. Experimental parameters included ionizing radiation (IR-induced cell death (AnnexinV, induction and repair of DNA strand breaks (Comet assay, induction of yH2AX foci (as a result of DNA double strand breaks, and whole genome expression analyses. Considerable inter-individual differences in IR-induced DNA strand breaks and their repair and/or cell death could be detected in primary and immortalised cells with the applied assays. The group of clinically radiosensitive patients was not unequivocally distinguishable from normal responding patients nor were individual overreacting patients in the test system unambiguously identified by two different laboratories. Thus, the in vitro test systems investigated here seem not to be appropriate for a general prediction of clinical reactions during or after radiotherapy due to the experimental variability compared to the small effect of radiation sensitivity. Genome-wide expression analysis however revealed a set of 67 marker genes which were differentially induced 6 h after in vitro-irradiation in lymphocytes from radio-hypersensitive and non-radiosensitive patients. These results warrant future validation in larger

  4. Psychosocial biomarker research: integrating social, emotional and economic factors into population studies of aging and health.

    Science.gov (United States)

    Steptoe, Andrew

    2011-04-01

    There are complex reciprocal relationships between health and social, emotional and economic factors in aging populations. Social and affective neurosciences are rapidly developing an understanding of the mechanisms underlying these phenomena using sophisticated behavioural, neuroimaging and psychophysiological methods. These techniques are often complex and expensive, so are generally used in relatively small selected samples rather than in large-scale cohort studies. However, an understanding of the significance of these processes in health and well-being depends on integrating findings from social and affective neuroscience into population-level studies. The aim of this article is to describe how a population perspective on the determinants of health and well-being in old age articulates with the agenda of social, affective and economic neuroscience, particularly through the application of psychosocial biomarker research. Social and affective neuroscience and epidemiological approaches provide complementary research strategies for understanding the mechanisms linking social, emotional and economic factors with health risk. This will be illustrated primarily from findings from two studies conducted at University College London, the Whitehall II Study and the English Longitudinal Study of Ageing.

  5. Biomarkers in major depressive disorder: the role of mass spectrometry.

    Science.gov (United States)

    Woods, Alisa G; Iosifescu, Dan V; Darie, Costel C

    2014-01-01

    Major depressive disorder (MDD) is common. Despite numerous available treatments, many individuals fail to improve clinically. MDD continues to be diagnosed exclusively via behavioral rather than biological methods. Biomarkers-which include measurements of genes, proteins, and patterns of brain activity-may provide an important objective tool for the diagnosis of MDD or in the rational selection of treatments. Proteomic analysis and validation of its results as biomarkers is less explored than other areas of biomarker research in MDD. Mass spectrometry (MS) is a comprehensive, unbiased means of proteomic analysis, which can be complemented by directed protein measurements, such as Western Blotting. Prior studies have focused on MS analysis of several human biomaterials in MDD, including human post-mortem brain, cerebrospinal fluid (CSF), blood components, and urine. Further studies utilizing MS and proteomic analysis in MDD may help solidify and establish biomarkers for use in diagnosis, identification of new treatment targets, and understanding of the disorder. The ultimate goal is the validation of a biomarker or a biomarker signature that facilitates a convenient and inexpensive predictive test for depression treatment response and helps clinicians in the rational selection of next-step treatments.

  6. Biomarkers of systemic lupus erythematosus identified using mass spectrometry-based proteomics: a systematic review.

    Science.gov (United States)

    Nicolaou, Orthodoxia; Kousios, Andreas; Hadjisavvas, Andreas; Lauwerys, Bernard; Sokratous, Kleitos; Kyriacou, Kyriacos

    2016-11-23

    Advances in mass spectrometry technologies have created new opportunities for discovering novel protein biomarkers in systemic lupus erythematosus (SLE). We performed a systematic review of published reports on proteomic biomarkers identified in SLE patients using mass spectrometry-based proteomics and highlight their potential disease association and clinical utility. Two electronic databases, MEDLINE and EMBASE, were systematically searched up to July 2015. The methodological quality of studies included in the review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-five studies were included in the review, identifying 241 SLE candidate proteomic biomarkers related to various aspects of the disease including disease diagnosis and activity or pinpointing specific organ involvement. Furthermore, 13 of the 25 studies validated their results for a selected number of biomarkers in an independent cohort, resulting in the validation of 28 candidate biomarkers. It is noteworthy that 11 candidate biomarkers were identified in more than one study. A significant number of potential proteomic biomarkers that are related to a number of aspects of SLE have been identified using mass spectrometry proteomic approaches. However, further studies are required to assess the utility of these biomarkers in routine clinical practice.

  7. Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

    Science.gov (United States)

    Dreussi, Eva; Cecchin, Erika; Polesel, Jerry; Canzonieri, Vincenzo; Agostini, Marco; Boso, Caterina; Belluco, Claudio; Buonadonna, Angela; Lonardi, Sara; Bergamo, Francesca; Gagno, Sara; De Mattia, Elena; Pucciarelli, Salvatore; De Paoli, Antonino; Toffoli, Giuseppe

    2016-01-01

    Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses. PMID:27608007

  8. [Biomarkers in Alzheimer's disease].

    Science.gov (United States)

    García-Ribas, G; López-Sendón Moreno, J L; García-Caldentey, J

    2014-04-01

    The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is already known that these pathological processes of AD starts decades before the first symptoms, so these biomarkers may provide means of early disease detection. At least three stages of AD could be identified: preclinical AD, mild cognitive impairment due to AD, and dementia due to AD. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review the actual research on blood-based biomarkers. Recent studies on healthy elderly subjects and on carriers of dominantly inherited AD mutations have also found biomarker changes that allow separate groups in these preclinical stages. These studies may aid for segregate populations in clinical trials and objectively evaluate if there are changes over the pathological processes of AD. Limits to widespread use of CSF biomarkers, apart from the invasive nature of the process itself, is the higher coefficient of variation for the analyses between centres. It requires strict pre-analytical and analytical procedures that may make feasible multi-centre studies and global cut-off points for the different stages of AD.

  9. The liver toxicity biomarker study: phase I design and preliminary results.

    Science.gov (United States)

    McBurney, Robert N; Hines, Wade M; Von Tungeln, Linda S; Schnackenberg, Laura K; Beger, Richard D; Moland, Carrie L; Han, Tao; Fuscoe, James C; Chang, Ching-Wei; Chen, James J; Su, Zhenqiang; Fan, Xiao-Hui; Tong, Weida; Booth, Shelagh A; Balasubramanian, Raji; Courchesne, Paul L; Campbell, Jennifer M; Graber, Armin; Guo, Yu; Juhasz, Peter J; Li, Tricin Y; Lynch, Moira D; Morel, Nicole M; Plasterer, Thomas N; Takach, Edward J; Zeng, Chenhui; Beland, Frederick A

    2009-01-01

    Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an innovative approach to investigate DILI because it compares molecular events produced in vivo by compound pairs that (a) are similar in structure and mechanism of action, (b) are associated with few or no signs of liver toxicity in preclinical studies, and (c) show marked differences in hepatotoxic potential. The LTBS is a collaborative preclinical research effort in molecular systems toxicology between the National Center for Toxicological Research and BG Medicine, Inc., and is supported by seven pharmaceutical companies and three technology providers. In phase I of the LTBS, entacapone and tolcapone were studied in rats to provide results and information that will form the foundation for the design and implementation of phase II. Molecular analysis of the rat liver and plasma samples combined with statistical analyses of the resulting datasets yielded marker analytes, illustrating the value of the broad-spectrum, molecular systems analysis approach to studying pharmacological or toxicological effects.

  10. Effect of a 16 weeks weight loss program on osteoarthritis biomarkers in obese patients with knee osteoarthritis: a prospective cohort study

    DEFF Research Database (Denmark)

    Bartels, E. M.; Christensen, Jeanette Reffstrup; Christensen, P.;

    2014-01-01

    Objective: Changes in biomarkers for bone and cartilage in knee osteoarthritis (KOA) may reflect changes in tissue turnover induced by interventions. The aim of this study was to assess the effect on osteoarthritis biomarkers of an intensive weight loss intervention in obese KOA patients. Methods...

  11. Relative validity of a food frequency questionnaire used in the Inter99 study

    DEFF Research Database (Denmark)

    Toft, U.; Kristoffersen, Lars; Ladelund, S.

    2008-01-01

    OBJECTIVE: To evaluate the validity of the Inter99 food frequency questionnaire (FFQ) compared with a 28-days' diet history and biomarkers. SUBJECTS: A random sample of 13 016 individuals were drawn from a general population and invited for a health screening programme. Participation rate was 52...... classification of individuals according to their dietary intakes and the FFQ gives a good quantitative measurement of key dietary components....

  12. Biomarkers, designs, and interpretations of resting-state fMRI in translational pharmacological research: A review of state-of-the-Art, challenges, and opportunities for studying brain chemistry.

    Science.gov (United States)

    Khalili-Mahani, Najmeh; Rombouts, Serge A R B; van Osch, Matthias J P; Duff, Eugene P; Carbonell, Felix; Nickerson, Lisa D; Becerra, Lino; Dahan, Albert; Evans, Alan C; Soucy, Jean-Paul; Wise, Richard; Zijdenbos, Alex P; van Gerven, Joop M

    2017-04-01

    A decade of research and development in resting-state functional MRI (RSfMRI) has opened new translational and clinical research frontiers. This review aims to bridge between technical and clinical researchers who seek reliable neuroimaging biomarkers for studying drug interactions with the brain. About 85 pharma-RSfMRI studies using BOLD signal (75% of all) or arterial spin labeling (ASL) were surveyed to investigate the acute effects of psychoactive drugs. Experimental designs and objectives include drug fingerprinting dose-response evaluation, biomarker validation and calibration, and translational studies. Common biomarkers in these studies include functional connectivity, graph metrics, cerebral blood flow and the amplitude and spectrum of BOLD fluctuations. Overall, RSfMRI-derived biomarkers seem to be sensitive to spatiotemporal dynamics of drug interactions with the brain. However, drugs cause both central and peripheral effects, thus exacerbate difficulties related to biological confounds, structured noise from motion and physiological confounds, as well as modeling and inference testing. Currently, these issues are not well explored, and heterogeneities in experimental design, data acquisition and preprocessing make comparative or meta-analysis of existing reports impossible. A unifying collaborative framework for data-sharing and data-mining is thus necessary for investigating the commonalities and differences in biomarker sensitivity and specificity, and establishing guidelines. Multimodal datasets including sham-placebo or active control sessions and repeated measurements of various psychometric, physiological, metabolic and neuroimaging phenotypes are essential for pharmacokinetic/pharmacodynamic modeling and interpretation of the findings. We provide a list of basic minimum and advanced options that can be considered in design and analyses of future pharma-RSfMRI studies. Hum Brain Mapp 38:2276-2325, 2017. © 2017 Wiley Periodicals, Inc.

  13. Biomarkers of air pollution exposure-A study of policemen in Prague

    Energy Technology Data Exchange (ETDEWEB)

    Topinka, J. [Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic and the Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic)], E-mail: jtopinka@biomed.cas.cz; Sevastyanova, O.; Binkova, B.; Chvatalova, I.; Milcova, A.; Lnenickova, Z.; Novakova, Z.; Solansky, I.; Sram, R.J. [Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic and the Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic)

    2007-11-01

    The effect of exposure to organic compounds adsorbed onto respirable air particles (<2.5 {mu}m) on DNA adducts in lymphocytes was studied in a group of non-smoking policemen (N = 109, aged 35 {+-} 0.9 years) working in the downtown area of Prague and spending >8 h daily outdoors. Personal exposure to carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) adsorbed on respirable particles was monitored in each subject for 48 h before biological sampling. DNA adducts were analyzed by a {sup 32}P-postlabelling assay, and total DNA adduct levels and B[a]P-like spots were determined. Further biomarkers included cotinine levels in urine to control for exposure to tobacco smoke, plasma levels of vitamins A, E and C and polymorphisms of metabolic genotypes (GSTM1, GSTP1, GSTT1, CYP 1A1-Msp I and Ile/Val, MTHFR, MS), DNA repair genotypes (XRCC1, hOGG1 and XPD exons 6 and 23) and the p53 gene (p53 Msp I and BstU I). All the biomarkers of exposure and effect were analyzed repeatedly during a period of one year at 2-3 month intervals (January, March, June, September 2004) to cover periods with high (winter) and low (summer) levels of air pollution. The highest personal exposure to c-PAHs was found in January (8.1 {+-} 8.8 ng/m{sup 3}), while the other three sampling periods exhibited 3-4-fold lower c-PAH exposure. The total DNA adducts were only slightly elevated in January (2.08 {+-} 1.60) compared to March (1.66 {+-} 0.65), June (1.96 {+-} 1.73) and September (1.77 {+-} 1.77). B[a]P-like DNA adducts, however, were significantly higher in January than in the March and June sampling periods (0.26 {+-} 0.14 vs. 0.19 {+-} 0.12 and 0.22 {+-} 0.13, respectively; p < 0.0001 and p = 0.017) indicating that c-PAH exposure probably plays a crucial role in DNA adduct formation in lymphocytes. No effect of individual metabololic or DNA repair genotypes on DNA adduct levels was observed. However, the combination of two genotypes encoding enzymes metabolizing c-PAHs - CYP 1A1 and GSTM1

  14. Copper toxicity induced hepatocerebral and neurodegenerative diseases: an urgent need for prognostic biomarkers.

    Science.gov (United States)

    Pal, Amit

    2014-01-01

    Copper (Cu) has been the subject of intensive research over several decades as numerous evidence robustly support the involvement of excess Cu induced neurotoxicity in hepatocerebral (Wilson's disease) and neurodegenerative disorders (especially Alzheimer's disease and Parkinson's disease); notwithstanding, the ideal Cu neurotoxicity biomarker/s for early prognosis remains elusive. Non-ceruloplasmin bound Cu is a biological marker of Wilson's disease and recent studies have shown that its levels are also increased in Alzheimer's disease. Copper chaperone for superoxide dismutase seems to be the other most promising biomarker of Cu toxicity (subject to its validation). Serum/plasma Cu, urine Cu and ceruloplasmin concentrations, most widely used laboratory indicators to diagnose Wilson's disease, are not specific for Cu excess milieu as these are also influenced by age, sex, inflammation and hormonal status. High inter-individual variability, nonexistence of standardized assays and non-specificity limit the use of other cuproenzymes as biomarkers of Cu neurotoxicity. The majority of Cu neurotoxicity biomarker research has focused in plasma/serum where other factors including inflammation, oxidative stress, dietary and environmental factors influence the Cu condition being studied. Proteomics study of cerebrospinal fluid, due to its high specificity and sensitivity represents an alternative approach to study early peripheral Cu neurotoxicity biomarker/s in experimental animals. In addition, network biology, transcriptomics in conjunction with novel in vivo Cu imaging techniques allow us to explore other potential candidates and propose new targets to be studied for chronic Cu neurotoxicity biomarker/s, and for possible therapeutic interventions.

  15. Biomarkers of dietary intake of flavonoids and phenolic acids for studying diet-cancer relationship in humans.

    OpenAIRE

    2008-01-01

    BACKGROUND: For many polyphenolic compounds found in plant-derived food, biological effects possibly relevant for cancer prevention have been shown. Since dietary intake estimates suffer from imprecision, the measurement of these compounds (or metabolites of) in biological specimens collected in epidemiological studies is expected to improve accuracy of exposure estimation. AIM OF THE STUDY: The current use of biomarkers in etiologic studies on polyphenolics and cancer risk is evaluated. In a...

  16. 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 BACKGROUND: 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. OBJECTIVE: To identify novel candidate biomarkers associated with disease severity in SMA using unbiased proteomic, metabolomic and transcriptomic approaches. MATERIALS AND METHODS: 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. RESULTS: 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. DISCUSSION: 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

  17. MicroRNA as potential biomarkers in Glioblastoma.

    Science.gov (United States)

    Areeb, Zammam; Stylli, Stanley S; Koldej, Rachel; Ritchie, David S; Siegal, Tali; Morokoff, Andrew P; Kaye, Andrew H; Luwor, Rodney B

    2015-11-01

    Glioblastoma is the most aggressive and lethal tumour of the central nervous system and as such the identification of reliable prognostic and predictive biomarkers for patient survival and tumour recurrence is paramount. MicroRNA detection has rapidly emerged as potential biomarkers, in patients with glioblastoma. Over the last decade, analysis of miRNA in laboratory based studies have yielded several candidates as potential biomarkers however, the accepted use of these candidates in the clinic is yet to be validated. Here we will examine the use of miRNA signatures to improve glioblastoma stratification into subgroups and summarise recent advances made in miRNA examination as potential biomarkers for glioblastoma progression and recurrence.

  18. Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility

    Directory of Open Access Journals (Sweden)

    Ashok Agarwal

    2016-01-01

    Full Text Available To study the major differences in the distribution of spermatozoa proteins in infertile men with varicocele by comparative proteomics and validation of their level of expression. The study-specific estimates for each varicocele outcome were combined to identify the proteins involved in varicocele-associated infertility in men irrespective of stage and laterality of their clinical varicocele. Expression levels of 5 key proteins (PKAR1A, AK7, CCT6B, HSPA2, and ODF2 involved in stress response and sperm function including molecular chaperones were validated by Western blotting. Ninety-nine proteins were differentially expressed in the varicocele group. Over 87% of the DEP involved in major energy metabolism and key sperm functions were underexpressed in the varicocele group. Key protein functions affected in the varicocele group were spermatogenesis, sperm motility, and mitochondrial dysfunction, which were further validated by Western blotting, corroborating the proteomics analysis. Varicocele is essentially a state of energy deprivation, hypoxia, and hyperthermia due to impaired blood supply, which is corroborated by down-regulation of lipid metabolism, mitochondrial electron transport chain, and Krebs cycle enzymes. To corroborate the proteomic analysis, expression of the 5 identified proteins of interest was validated by Western blotting. This study contributes toward establishing a biomarker "fingerprint" to assess sperm quality on the basis of molecular parameters.

  19. 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.

  20. Current studies of biomarkers for the early diagnosis of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Chandrashekara S

    2014-09-01

    Full Text Available S Chandrashekara ChanRe Rheumatology and Immunology Center and Research, Basaveshwaranagar, Bangalore, India Abstract: Early treatment of rheumatoid arthritis (RA with disease-modifying antirheumatic drugs will improve the outcome significantly. Early diagnosis of RA continues to be a challenge. The disease needs to be distinguished from other self-limiting arthritis and connective tissue disease. Currently available autoantibodies like rheumatoid factors and anticitrullinated cyclic peptide have limited sensitivity and specificity. RA, being a heterogeneous disease, with no unique or distinct defect that has been described, is less likely to have a single pathognomonic marker. There are defined predisposing genetic factors, cell characteristics, cytokine changes, autoantibodies, and products of disease process that have been demonstrated to distinguish rheumatoid from normal and other arthritis. Studies have demonstrated that combinations of factors allow for more specific RA diagnosis; however, when considerations are given to the factors separately, sensitivity increases at the cost of specificity. The present review briefly describes the value of some of the candidate factors and their combinations as diagnostic markers of early RA. Well-designed multicenter studies to evaluate these combinations using a scoring system are recommended for the development of precise and widely applicable biomarkers for early diagnosis of RA. Keywords: autoantibodies, combination, early RA, specificity

  1. Potassium Dichromate Impact on Male Reproductive Integrity Biomarker in Rat. Two Generation Study

    Directory of Open Access Journals (Sweden)

    Jelena Rankov

    2010-05-01

    Full Text Available The aim of this study was the evaluation of Cr VI cumulative and differentiate exposure on integrity biomarker of male reproductive system. The objective was evaluation of potassium dichromate intake on genital organs and sexual accessory glands architecture in male rats from two generation. Males and females from F0 generation were exposed to potassium dichromate three months before mating. F1 generation was represented by male pups, resulted from F0 generation, exposed to potassium dichromate in utero, during suckling (via milk and water period and until sexual maturity. All the animals were divided in one control and three experimental groups, exposed to Cr VI trough drinking water, as followed E1: 25 ppm (LOAEL; E2: 50 ppm: E3: 75 ppm; control group received tap water without chromium content. The experiment was carried out with respecting legislation regarding ethics in animal experiments. The study revealed the presence of congestive and degenerative lesions in genital organs and sexual accessory glands of exposed individuals from F0 and F1 generation such as: interstitial edema, epithelial necrosis and atrophy, membrane exfoliation and necrosis. The lesions frequency and intensity were directly correlated to exposure level, the most affected being E3 group and generation, more pronounced in F1 generation.

  2. Diet, Lifestyle, Biomarkers, Genetic Factors, and Risk of Cardiovascular Disease in the Nurses’ Health Studies

    Science.gov (United States)

    Yu, Edward; Rimm, Eric; Qi, Lu; Rexrode, Kathryn; Albert, Christine M.; Sun, Qi; Willett, Walter C.; Manson, JoAnn E.

    2016-01-01

    Objectives. To review the contributions of the Nurses’ Health Studies (NHSs) to the understanding of cardiovascular disease etiology in women. Methods. We performed a narrative review of the publications of the NHS and NHS II between 1976 and 2016. Results. Diets low in trans fat, saturated fat, refined carbohydrates, and sugar-sweetened beverages and rich in fruits and vegetables, whole grains, and sources of unsaturated fats are associated with reduced risk of cardiovascular disease. Healthy lifestyle choices include smoking avoidance, regular physical activity, maintaining a normal body mass index, and moderate alcohol consumption. Adherence to a combination of these healthy diet and lifestyle behaviors may prevent most vascular events. Studies also covered oral contraceptive use, postmenopausal hormone therapy, shift work, sleep duration, psychosocial factors, and various biomarkers and genetic factors. Findings, such as the association of trans fat with cardiovascular disease, have helped shaped medical guidelines and government policies. Conclusions. The NHS has provided compelling evidence that the majority of vascular events may be prevented by avoiding smoking, participating in regular physical activity, maintaining normal body mass index, and eating a healthy diet. PMID:27459449

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

    Science.gov (United States)

    Freitas, Erika P. S.; Cunha, Aline T. O.; Aquino, Sephora L. S.; Pedrosa, Lucia F. C.; Lima, Severina C. V. C.; Lima, Josivan G.; Almeida, Maria G.; Sena-Evangelista, Karine C. M.

    2017-01-01

    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 0.05) between the two groups. We found significantly higher erythrocyte zinc concentration in the MS group (p 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. PMID:28241426

  4. Commentary: statistics for biomarkers.

    Science.gov (United States)

    Lovell, David P

    2012-05-01

    This short commentary discusses Biomarkers' requirements for the reporting of statistical analyses in submitted papers. It is expected that submitters will follow the general instructions of the journal, the more detailed guidance given by the International Committee of Medical Journal Editors, the specific guidelines developed by the EQUATOR network, and those of various specialist groups. Biomarkers expects that the study design and subsequent statistical analyses are clearly reported and that the data reported can be made available for independent assessment. The journal recognizes that there is continuing debate about different approaches to statistical science. Biomarkers appreciates that the field continues to develop rapidly and encourages the use of new methodologies.

  5. THE SPORT IMAGERY QUESTIONNAIRE: A STUDY OF VALIDITY AND RELIABILITY

    Directory of Open Access Journals (Sweden)

    Muhammed Emin KAFKAS

    2011-08-01

    Full Text Available The aim of this research is to adapt The Sport Imagery Questionnaire (Hall, Munroe-Chandler, Fishburne ve Hall, 2009 into Turkish and to examine its psychometric properties. The research was conducted on 208 female (38.2% and 337 male (61.8% volunteering students aged mostly between 12-16 studying at 1st and 2nd stage of primary schools affiliated to central district of Malatya province, Turkey. First the linguistic equivalence of the scale was tested, which is then followed by validity and reliability studies. Internal consistency coefficients varied between .66-.87 and test-retest reliability coefficients varied between .60-.86. Corrected item-total correlations ranged from .60 to .85. Based on these results the Sport Imagery Questionnaire can be used as a valid and reliable instrument.

  6. Pathogen specific biomarkers for the diagnosis of tuberculosis in deer

    Science.gov (United States)

    Objective - To develop a noninvasive biomarker based Mycobacterium bovis specific detection system to track infection in domestic and wild animals. Design – Experimental longitudinal study for discovery and cross sectional design for validation Animals - Yearling white-tailed deer fawns (n=8) were ...

  7. Biomarker time out.

    Science.gov (United States)

    Petzold, Axel; Bowser, Robert; Calabresi, Paolo; Zetterberg, Henrik; Uitdehaag, Bernard M J

    2014-10-01

    The advancement of knowledge relies on scientific investigations. The timing between asking a question and data collection defines if a study is prospective or retrospective. Prospective studies look forward from a point in time, are less prone to bias and are considered superior to retrospective studies. This conceptual framework conflicts with the nature of biomarker research. New candidate biomarkers are discovered in a retrospective manner. There are neither resources nor time for prospective testing in all cases. Relevant sources for bias are not covered. Ethical questions arise through the time penalty of an overly dogmatic concept. The timing of sample collection can be separated from testing biomarkers. Therefore the moment of formulating a hypothesis may be after sample collection was completed. A conceptual framework permissive to asking research questions without the obligation to bow to the human concept of calendar time would simplify biomarker research, but will require new safeguards against bias.

  8. Selection of reliable biomarkers from PCR array analyses using relative distance computational model: methodology and proof-of-concept study.

    Directory of Open Access Journals (Sweden)

    Chunsheng Liu

    Full Text Available It is increasingly evident about the difficulty to monitor chemical exposure through biomarkers as almost all the biomarkers so far proposed are not specific for any individual chemical. In this proof-of-concept study, adult male zebrafish (Danio rerio were exposed to 5 or 25 µg/L 17β-estradiol (E2, 100 µg/L lindane, 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or 15 mg/L arsenic for 96 h, and the expression profiles of 59 genes involved in 7 pathways plus 2 well characterized biomarker genes, vtg1 (vitellogenin1 and cyp1a1 (cytochrome P450 1A1, were examined. Relative distance (RD computational model was developed to screen favorable genes and generate appropriate gene sets for the differentiation of chemicals/concentrations selected. Our results demonstrated that the known biomarker genes were not always good candidates for the differentiation of pair of chemicals/concentrations, and other genes had higher potentials in some cases. Furthermore, the differentiation of 5 chemicals/concentrations examined were attainable using expression data of various gene sets, and the best combination was the set consisting of 50 genes; however, as few as two genes (e.g. vtg1 and hspa5 [heat shock protein 5] were sufficient to differentiate the five chemical/concentration groups in the present test. These observations suggest that multi-parameter arrays should be more reliable for biomonitoring of chemical exposure than traditional biomarkers, and the RD computational model provides an effective tool for the selection of parameters and generation of parameter sets.

  9. Selection of reliable biomarkers from PCR array analyses using relative distance computational model: methodology and proof-of-concept study.

    Science.gov (United States)

    Liu, Chunsheng; Xu, Hongyan; Lam, Siew Hong; Gong, Zhiyuan

    2013-01-01

    It is increasingly evident about the difficulty to monitor chemical exposure through biomarkers as almost all the biomarkers so far proposed are not specific for any individual chemical. In this proof-of-concept study, adult male zebrafish (Danio rerio) were exposed to 5 or 25 µg/L 17β-estradiol (E2), 100 µg/L lindane, 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 15 mg/L arsenic for 96 h, and the expression profiles of 59 genes involved in 7 pathways plus 2 well characterized biomarker genes, vtg1 (vitellogenin1) and cyp1a1 (cytochrome P450 1A1), were examined. Relative distance (RD) computational model was developed to screen favorable genes and generate appropriate gene sets for the differentiation of chemicals/concentrations selected. Our results demonstrated that the known biomarker genes were not always good candidates for the differentiation of pair of chemicals/concentrations, and other genes had higher potentials in some cases. Furthermore, the differentiation of 5 chemicals/concentrations examined were attainable using expression data of various gene sets, and the best combination was the set consisting of 50 genes; however, as few as two genes (e.g. vtg1 and hspa5 [heat shock protein 5]) were sufficient to differentiate the five chemical/concentration groups in the present test. These observations suggest that multi-parameter arrays should be more reliable for biomonitoring of chemical exposure than traditional biomarkers, and the RD computational model provides an effective tool for the selection of parameters and generation of parameter sets.

  10. 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

  11. The Potential Utility of Urinary Biomarkers for Risk Prediction in Combat Casualties: A Prospective Observational Cohort Study

    Science.gov (United States)

    2015-06-16

    associated with adverse outcomes in acute renal failure . J Am Soc Nephrol. 2007;18:904–12. 14. Alge JL. Arthur JM. Biomarkers of AKI: a review of mechanistic...are associated with poor outcomes, including death and the need for renal replacement therapy. Methods: We conducted a prospective, observational study...Eighty nine patients with urine samples drawn at admission to the intensive care unit were studied. Twelve patients subsequently died or needed renal

  12. Estimation of biomarkers berberine and gallic acid in polyherbal formulation punarnavashtak kwath and its clinical study for hepatoprotective potential

    OpenAIRE

    Shah V; Doshi D; Shah M; Bhatt P

    2010-01-01

    Punarnavashtak (PN) kwath is a classical Ayurvedic formulation mentioned in Ayurvedic literature "Bhaishyajyaratnavali" for hepatic disorders and asthma. Standardization and clinical trial to support its efficacy are lacking. So, in the present study, standardization of PN kwath was done by using biomarkers, gallic acid and berberine, and its hepatoprotective activity was evaluated by clinical study to rationalise the traditional use of this formulation. PN kwath was standardized by HPTLC (Hi...

  13. Using biomarkers to predict treatment response in major depressive disorder: evidence from past and present studies.

    Science.gov (United States)

    Thase, Michael E

    2014-12-01

    Major depressive disorder (MDD) is a heterogeneous condition with a variable response to a wide range of treatments. Despite intensive efforts, no biomarker has been identified to date that can reliably predict response or non-response to any form of treatment, nor has one been identified that can be used to identify those at high risk of developing treatment-resistant depression (ie, non-response to a sequence of treatments delivered for adequate duration and intensity). This manuscript reviews some past areas of research that have proved informative, such as studies using indexes of hypercortisolism or sleep disturbance, and more recent research findings using measures of inflammation and different indicators of regional cortical activation to predict treatment response. It is concluded that, although no method has yet been demonstrated to be sufficiently accurate to be applied in clinical practice, progress has been made. It thus seems likely that--at some point in the not-too-distant future--it will be possible to prospectively identify, at least for some MDD patients, the likelihood of response or non-response to cognitive therapy or various antidepressant medications.

  14. Plasma micro-RNA biomarkers for diagnosis and prognosis after traumatic brain injury: A pilot study.

    Science.gov (United States)

    Mitra, Biswadev; Rau, Thomas F; Surendran, Nanda; Brennan, James H; Thaveenthiran, Prasanthan; Sorich, Edmond; Fitzgerald, Mark C; Rosenfeld, Jeffrey V; Patel, Sarjubhai A

    2017-04-01

    Prediction of post-concussive syndrome after apparent mild traumatic brain injury (TBI) and subsequent cognitive recovery remains challenging, with substantial limitations of current methods of cognitive testing. This pilot study aimed to determine if levels of micro ribonucleic acids (RNAs) circulating in plasma are altered following TBI, and if changes to levels of such biomarkers over time could assist in determination of prognosis after TBI. Patients were enrolled after TBI on presentation to the Emergency Department and allocated to three groups: A - TBI (physical trauma to the head), witnessed loss of consciousness, amnesia, GCS=15, a normal CT Brain and a recorded first pass after post-traumatic amnesia (PTA) scale; B TBI, witnessed LOC, amnesia, GCS=15, a normal CT brain and a PTA scale test fail and: C - TBI and initial GCS RNA was then assayed using a custom miRNA PCR array. Two micro-RNAs, mir142-3p and mir423-3p demonstrated potential clinical utility differentiating patients after mild head injury into those at greater risk of developing amnesia and therefore, post-concussive syndromes. In addition, these miRNA demonstrated a decrease in expression over time, possibly indicative of brain healing after the injury. Further evaluation of these identified miRNA markers with larger patient cohorts, correlation with clinical symptoms and analysis over longer time periods are essential next steps in developing objective markers of severity of TBI.

  15. The future of liquid chromatography-mass spectrometry in metabolic profiling and metabolomic studies for biomarker discovery.

    Energy Technology Data Exchange (ETDEWEB)

    Metz, Thomas O.; Zhang, Qibin; Page, Jason S.; Shen, Yufeng; Callister, Stephen J.; Jacobs, Jon M.; Smith, Richard D.

    2007-06-01

    The future utility of liquid chromatography-mass spectrometry (LC-MS) in metabolic profiling and metabolomic studies for biomarker discover will be discussed, beginning with a brief description of the evolution of metabolomics and the utilization of the three most popular analytical platforms in such studies: NMR, GC-MS, and LC-MS. Emphasis is placed on recent developments in high-efficiency LC separations and sensitive electrospray ionization approaches and the benefits to incorporating both in LC-MS-based approaches. The advantages and disadvantages of various quantitative approaches are reviewed, followed by the current LC-MS-based tools available for candidate biomarker characterization and identification. Finally, a brief prediction on the future path of LC-MS-based methods in metabolic profiling and metabolomic studies is given.

  16. The Dutch Marital Satisfaction and Communication Questionnaire: A Validation study

    Directory of Open Access Journals (Sweden)

    Ann Van den Troost

    2005-09-01

    Full Text Available The purpose of this study is to validate the Dutch Marital Satisfaction and Communication Questionnaire (DMSCQ, a 16-item measure that disentangles marital satisfaction, negative communication and open communication. In three subsequent studies empirical evidence for the construct and criterion validity is presented using (confirmatory factor analyses, and correlational analyses with criterion variables. Results indicate that the 16 items represent a solid three-factor structure, which was replicated across time and in independent samples. High agreement in factor structure between men and women was demonstrated by high levels of Tucker's coefficient of congruence. The internal consistencies of the marital satisfaction and negative communication scales are good; for the open communication scale it is somewhat lower but still acceptable. Consistent evidence was obtained for a negative relationship between the three marital outcomes and parental depression and conflictual family climate whereas the three former are positively related to life satisfaction and well-being. Spouses who feel restricted by their parental role or experience parenting stress tend to be less satisfied with their partnership and perceive the marital communication as more negative. Our results demonstrate that the DMSCQ provides a brief, valid and reliable measure of marital satisfaction, negative and open communication.

  17. Cancer Biomarkers | Division of Cancer Prevention

    Science.gov (United States)

    [[{"fid":"175","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Cancer Biomarkers Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Cancer Biomarkers Research Group Homepage Logo","field_folder[und]":"15"},"type":"media","attributes":{"alt":"Cancer Biomarkers Research Group Homepage Logo","title":"Cancer Biomarkers Research Group Homepage Logo","height":"266","width":"400","style":"width: 400px; height: 266px;","class":"i | Research to identify, develop and validate biomarkers for early cancer detection and risk assessment.

  18. 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

    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...... 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.......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...

  19. Blood biomarkers in metal scrap workers accidentally exposed to ionizing radiation: a case study.

    Science.gov (United States)

    Gupta, M L; Srivastava, N N; Dutta, S; Shukla, S K; Dutta, A; Verma, S; Devi, M

    2013-12-01

    The detrimental effect of nuclear accidents due to localized or whole body radiation exposure results in severe cellular damage. The current study was carried out to evaluate radiation-mediated variability in blood components of metal scrap workers exposed accidently to cobalt-60 source. Blood samples collected initially from five hospitalized patients, coded P1-P5, were processed for total leukocyte counts (TLC), platelet (PLT) counts, haemoglobin, estimation of DNA double strand breaks by measuring phosphorylated form of H2AX (γ-H2AX) and chromosomal aberrations (dicentrics). Blood cells count (TLC), in all the patients except P2, was found decreased. Dicentrics increased in all the five patients. γ-H2AX was found significantly elevated in patients P2 and P4. After 3 days, 21 subjects working in close vicinity of accident site were evaluated for the above-mentioned markers to confirm their possibility of radiation exposure; however, all the parameters in these subjects were found within normal limits. Blood from patients P1-P5 was collected again after 11 days. Studies revealed exorbitant increase in γ-H2AX in lymphocytes and monocytes of patients P1, P4 and P5. TLC and PLT count in these patients had fallen further. Dicentrics declined with time in all the five patients. Based on the studied blood biomarkers, we conclude that the five subjects showed signs of radiation exposure. Measurement on radiation dose could not be performed in the current study; however, the generated data particularly on dicentrics provide ample evidence of radiation exposure.

  20. Preliminary Study on Serum Lactate Dehydrogenase (LDH)-Prognostic Biomarker in Carcinoma Breast

    Science.gov (United States)

    Gandhe, Mahendra Bhauraoji; Gupta, Dilip; Reddy, M.V.R.

    2016-01-01

    Introduction Serum Lactate Dehydrogenase (LDH) is one of the biochemical markers for breast cancer. Serum LDH is enzyme required for anaerobic glycolysis. One of its isoenzyme is increased in breast cancer due to up-regulation in its gene. It leads to increase in serum LDH level in breast cancer patients. Serum LDH is economical, easily available and easy to estimate. Aim In the present study, we evaluated the LDH levels in circulation of newly diagnosed patients of breast cancer and tried to correlate it with different TNM staging of carcinoma breast before interventions and after adjuvant therapy of these patients. Materials and Methods This prospective study was done on 83 diagnosed patients of breast cancer was conducted among poor patients in rural area. This study was conducted in the Department of Surgery between October 2008 to October 2010, at MGIMS, Sevagram, Maharashtra, a rural medical college located in Central India. Out of total 83 participants, 10 participants were having adverse events following surgery and remaining 73 participants were without adverse events following surgery. The significant difference in serum LDH levels between two groups, with and without adverse surgical outcome was calculated by Mann-Whitney U test. Results Patients with higher clinical TNM staging were having higher serum LDH levels. The serum LDH levels at sixth months following surgery showed a trend of statistically significant difference between patients with and without adverse events. As increased serum LDH levels in breast cancer patients shows poor prognosis, surgical outcome or advanced metastases. Conclusion Serum LDH monitoring can be used as a prognostic biomarker in patients of breast cancer. For confirmation of this finding, we require further more studies on larger sample size and long-term follow-up in patients specifically with higher serum LDH levels. PMID:27134855

  1. Pilot study of the pharmacokinetics of betel nut and betel quid biomarkers in saliva, urine, and hair of betel consumers

    Science.gov (United States)

    Franke, Adrian A.; Li, Xingnan; Lai, Jennifer F.

    2016-01-01

    Approximately 600 million people worldwide practise the carcinogenic habit of betel nut/quid chewing. Carcinogenic N-nitroso compounds have been identified in saliva or urine of betel chewers and the betel alkaloid arecoline in hair from habitual betel quid chewers. However, the pharmacokinetic parameters of these compounds have been little explored. Assessment of betel use by biomarkers is urgently needed to evaluate the effectiveness of cessation programmes aimed at reducing betel consumption to decrease the burden of cancers in regions of high betel consumption. In the search for biomarkers of betel consumption, we measured by liquid chromatography-mass spectrometry (LC-MS) the appearance and disappearance of betel alkaloids (characteristic for betel nuts), N-nitroso compounds, and chavibetol (characteristic for Piper Betle leaves) in saliva (n=4), hair (n=2), and urine (n=1) of occasional betel nut/quid chewers. The betel alkaloids arecoline, guvacoline, guvacine, and arecaidine were detected in saliva of all four participants and peaked within the first 2 h post-chewing before returning to baseline levels after 8 h. Salivary chavibetol was detected in participants consuming Piper Betle leaves in their quid and peaked ~1 h post-chewing. Urinary arecoline, guvacoline, and arecaidine excretion paralleled saliva almost exactly while chavibetol glucuronide excretion paralleled salivary chavibetol. No betel nut related compounds were detected in the tested hair samples using various extraction methods. From these preliminary results, we conclude that betel exposure can only be followed on a short-term basis (≤8 h post-chewing) using the applied biomarkers from urine and saliva while the feasibility of using hair has yet to be validated. PMID:26619803

  2. Dissecting the Syndrome of Schizophrenia: Progress toward Clinically Useful Biomarkers

    Directory of Open Access Journals (Sweden)

    Brian Dean

    2011-01-01

    Full Text Available The search for clinically useful biomarkers has been one of the holy grails of schizophrenia research. This paper will outline the evolving notion of biomarkers and then outline outcomes from a variety of biomarkers discovery strategies. In particular, the impact of high-throughput screening technologies on biomarker discovery will be highlighted and how new or improved technologies may allow the discovery of either diagnostic biomarkers for schizophrenia or biomarkers that will be useful in determining appropriate treatments for people with the disorder. History tells those involved in biomarker research that the discovery and validation of useful biomarkers is a long process and current progress must always be viewed in that light. However, the approval of the first biomarker screen with some value in predicting responsiveness to antipsychotic drugs suggests that biomarkers can be identified and that these biomarkers that will be useful in diagnosing and treating people with schizophrenia.

  3. Dissecting the Syndrome of Schizophrenia: Progress toward Clinically Useful Biomarkers.

    Science.gov (United States)

    Dean, Brian

    2011-01-01

    The search for clinically useful biomarkers has been one of the holy grails of schizophrenia research. This paper will outline the evolving notion of biomarkers and then outline outcomes from a variety of biomarkers discovery strategies. In particular, the impact of high-throughput screening technologies on biomarker discovery will be highlighted and how new or improved technologies may allow the discovery of either diagnostic biomarkers for schizophrenia or biomarkers that will be useful in determining appropriate treatments for people with the disorder. History tells those involved in biomarker research that the discovery and validation of useful biomarkers is a long process and current progress must always be viewed in that light. However, the approval of the first biomarker screen with some value in predicting responsiveness to antipsychotic drugs suggests that biomarkers can be identified and that these biomarkers that will be useful in diagnosing and treating people with schizophrenia.

  4. 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 BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The majority of neurophysiological and

  5. Should plasma homocysteine be used as a biomarker of venous thromboembolism? A case-control study.

    Science.gov (United States)

    Ducros, Véronique; Barro, Claire; Yver, Jacqueline; Pernod, Gilles; Polack, Benoît; Carpentier, Patrick; Desruet, Marie-Dominique; Bosson, Jean-Luc

    2009-10-01

    Mild or moderate hyperhomocysteinemia as a risk factor for venous thrombosis is still a matter of debate. The strength of this study is to bring a body of elements to evaluate whether hyperhomocysteinemia should be used as a biomarker for venous thromboembolism (VTE). These elements consist of a biological evaluation of several hematological risk factors, and an original control group made of patients with a negative Doppler ultrasonography. A total of 151 cases and 155 controls were included. Total plasma homocysteine level, MTHFR C677T polymorphism, inherited abnormalities of the natural anticoagulant system as well as plasma folate and cobalamin levels were determined. A total of 41 (27.2 %) of cases and only 9 (5.8%) of controls had at least one of the coagulation defects studied. No significant difference was observed for total homocysteine levels between the 2 groups: median (interquartile range) = 8.3 (7.2-10.8) micromol/L for cases and 8.4 (7-10.9) micromol/L for controls. We found significantly more plasma folates and/or cobalamin deficiencies in controls (18.3%) than in cases (8.6%). After adjustment for several variables significantly related to risk factors of VTE, hyperhomocysteinemia (>13.2 micromol/L) was not found statistically associated with VTE: odds ratio 1.36 (95% confidence interval, 0.52-3.54). The prevalence of the homozygous 677TT polymorphism in the MTHFR gene was not increased in cases compared with controls. Mild or moderate hyperhomocysteinemia does not seem to be a strong determinant in VTE not only when the control group does not exclusively include healthy persons but also in investigated disease-free (thromboembolic disease) controls.

  6. Evaluation of chemotherapy response in ovarian cancer treatment using quantitative CT image biomarkers: a preliminary study

    Science.gov (United States)

    Qiu, Yuchen; Tan, Maxine; McMeekin, Scott; Thai, Theresa; Moore, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

    2015-03-01

    The purpose of this study is to identify and apply quantitative image biomarkers for early prediction of the tumor response to the chemotherapy among the ovarian cancer patients participated in the clinical trials of testing new drugs. In the experiment, we retrospectively selected 30 cases from the patients who participated in Phase I clinical trials of new drug or drug agents for ovarian cancer treatment. Each case is composed of two sets of CT images acquired pre- and post-treatment (4-6 weeks after starting treatment). A computer-aided detection (CAD) scheme was developed to extract and analyze the quantitative image features of the metastatic tumors previously tracked by the radiologists using the standard Response Evaluation Criteria in Solid Tumors (RECIST) guideline. The CAD scheme first segmented 3-D tumor volumes from the background using a hybrid tumor segmentation scheme. Then, for each segmented tumor, CAD computed three quantitative image features including the change of tumor volume, tumor CT number (density) and density variance. The feature changes were calculated between the matched tumors tracked on the CT images acquired pre- and post-treatments. Finally, CAD predicted patient's 6-month progression-free survival (PFS) using a decision-tree based classifier. The performance of the CAD scheme was compared with the RECIST category. The result shows that the CAD scheme achieved a prediction accuracy of 76.7% (23/30 cases) with a Kappa coefficient of 0.493, which is significantly higher than the performance of RECIST prediction with a prediction accuracy and Kappa coefficient of 60% (17/30) and 0.062, respectively. This study demonstrated the feasibility of analyzing quantitative image features to improve the early predicting accuracy of the tumor response to the new testing drugs or therapeutic methods for the ovarian cancer patients.

  7. Which biomarkers reveal neonatal sepsis?

    Directory of Open Access Journals (Sweden)

    Kun Wang

    Full Text Available We address the identification of optimal biomarkers for the rapid diagnosis of neonatal sepsis. We employ both canonical correlation analysis (CCA and sparse support vector machine (SSVM classifiers to select the best subset of biomarkers from a large hematological data set collected from infants with suspected sepsis from Yale-New Haven Hospital's Neonatal Intensive Care Unit (NICU. CCA is used to select sets of biomarkers of increasing size that are most highly correlated with infection. The effectiveness of these biomarkers is then validated by constructing a sparse support vector machine diagnostic classifier. We find that the following set of five biomarkers capture the essential diagnostic information (in order of importance: Bands, Platelets, neutrophil CD64, White Blood Cells, and Segs. Further, the diagnostic performance of the optimal set of biomarkers is significantly higher than that of isolated individual biomarkers. These results suggest an enhanced sepsis scoring system for neonatal sepsis that includes these five biomarkers. We demonstrate the robustness of our analysis by comparing CCA with the Forward Selection method and SSVM with LASSO Logistic Regression.

  8. Metaanalysis of Validity Studies Published Between 1964 and 1982 and the Investigation of Study Characteristics.

    Science.gov (United States)

    Schmitt, Neal; And Others

    1984-01-01

    Reviewed published validation studies for the years 1964-1982 of the Journal of Applied Psychology and Personnel Psychology. Results indicated minimal differences across study designs in the average validity coefficient and found selection ratios, standard deviations, reliabilities, predictor and criterion intercorrelations to be rarely and…

  9. Vascular biomarkers to predict response to exercise in Alzheimer's disease: the study protocol

    Science.gov (United States)

    Li, Danni; Thomas, Robin; Tsai, Michael Y; Li, Ling; Vock, David M; Greimel, Susan; Yu, Fang

    2016-01-01

    Introduction Exercise interventions are a promising treatment for improving cognition in persons with Alzheimer's disease. This is similar to Alzheimer's disease pharmacotherapies in which only 18–48% of treated patients demonstrate improvement in cognition. Aerobic exercise interventions positively affect brain structure and function through biologically sound pathways. However, an under-studied mechanism of aerobic exercise's effects is n-3 fatty acids in plasma. The objective of this pilot study is to inform a future large-scale study to develop n-3 fatty acids-based prediction of cognitive responses to aerobic exercise treatment in Alzheimer's disease. Methods and analysis This study will recruit and follow a cohort of 25 subjects enrolled in the FIT-AD Trial, an ongoing randomised controlled trial that investigates the effects of a 6-month moderate-intensity cycling intervention on cognition and hippocampal volume in older adults with mild to moderate Alzheimer's disease over a year. This study will collect blood from subjects at baseline and at 3 and 6 months to assay vascular biomarkers (ie, plasma fatty acids). Global cognition as measured by the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) at baseline, 3, 6, 9 and 12 months will be used as the main outcome. A multiple linear-regression model will be used with 12-month change in cognition as the outcome and baseline measure of n-3 fatty acids or changes in the ratio of n-3 to n-6 fatty-acid levels in plasma at 3 and/or 6 months, randomised treatment group, and their interaction as predictors. Ethics and dissemination We have obtained Institutional Review Board approval for our study. We obtain consent or assent/surrogate consent from all subjects depending on their consenting capacity assessment. Data of this study are/will be stored in the Research Electronic Data Capture (REDCap). We plan to present and publish our study findings through presentations and manuscripts. Trial

  10. Critical Analysis of Soil Invertebrate Biomarkers: A Field Case Study in Avonmouth, UK

    NARCIS (Netherlands)

    Weeks, J.M.; Spurgeon, D.J.; Svendsen, C.; Hankard, P.K.; Kammenga, J.E.; Dallinger, R.; Köhler, H.R.; Simonsen, V.; Scott-Fordsmand, J.

    2004-01-01

    During the period 1996–1999 a joint field research programme (BIOPRINT-II) funded by the European Union was undertaken. The main objective of this project was the deployment of biochemical fingerprint techniques of soil invertebrate biomarkers for assessing the exposure and effect of toxicants on so

  11. 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.

  12. Rationale and methods of the integrated biomarker and imaging study (IBIS): combining invasive and non-invasive imaging with biomarkers to detect subclinical atherosclerosis and assess coronary lesion biology.

    Science.gov (United States)

    Van Mieghem, Carlos A G; Bruining, Nico; Schaar, Johannes A; McFadden, Eugene; Mollet, Nico; Cademartiri, Filippo; Mastik, Frits; Ligthart, Jurgen M R; Granillo, Gaston A Rodriguez; Valgimigli, Marco; Sianos, Georgios; van der Giessen, Willem J; Backx, Bianca; Morel, Marie-Angele M; Van Es, Gerrit-Anne; Sawyer, Jonathon D; Kaplow, June; Zalewski, Andrew; van der Steen, Anton F W; de Feyter, Pim; Serruys, Patrick W

    2005-08-01

    Death or myocardial infarction, the most serious clinical consequences of atherosclerosis, often result from plaque rupture at non-flow limiting lesions. Current diagnostic imaging with coronary angiography only detects large plaques that already impinge on the lumen and cannot accurately identify those that have a propensity to cause unheralded events. Accurate evaluation of the composition or of the biomechanical characteristics of plaques with invasive or non-invasive methods, alone or in conjunction with assessment of circulating biomarkers, could help identify high-risk patients, thus providing the rationale for aggressive treatments in order to reduce future clinical events. The IBIS (Integrated Biomarker and Imaging Study) study is a prospective, single-center, non-randomized, observational study conducted in Rotterdam. The aim of the IBIS study is to evaluate both invasive (quantitative coronary angiography, intravascular ultrasound (IVUS) and palpography) and non-invasive (multislice spiral computed tomography) imaging techniques to characterize non-flow limiting coronary lesions. In addition, multiple classical and novel biomarkers will be measured and their levels correlated with the results of the different imaging techniques. A minimum of 85 patients up to a maximum of 120 patients will be included. This paper describes the study protocol and methodological solutions that have been devised for the purpose of comparisons among several imaging modalities. It outlines the analyses that will be performed to compare invasive and non-invasive imaging techniques in conjunction with multiple biomarkers to characterize non-flow limiting subclinical coronary lesions.

  13. Annotations on Mexico's WISC-IV: a validity study.

    Science.gov (United States)

    Fina, Anthony D; Sánchez-Escobedo, Pedro; Hollingworth, Liz

    2012-01-01

    This project seeks to provide evidence on the internal structure of the Escala Wechsler de Inteligencia para Niños-IV (EWIN-IV; Wechsler, 2007a ) through a confirmatory factor analysis and intercorrelational study. Also provided is information on the adaptation process and other sources of validity evidence in support of the EWIN-IV norms. The standardization data for the EWIN-IV were used for all analyses. The factor loadings and correlational patterns found on the EWIN-IV are comparable to those seen in the American versions of the test. The proposed factor and scoring structure of the EWIN-IV was supported.

  14. Acute kidney injury biomarkers for patients in a coronary care unit: a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Tien-Hsing Chen

    Full Text Available BACKGROUND: Renal dysfunction is an established predictor of all-cause mortality in intensive care units. This study analyzed the outcomes of coronary care unit (CCU patients and evaluated several biomarkers of acute kidney injury (AKI, including neutrophil gelatinase-associated lipocalin (NGAL, interleukin-18 (IL-18 and cystatin C (CysC on the first day of CCU admission. METHODOLOGY/PRINCIPAL FINDINGS: Serum and urinary samples collected from 150 patients in the coronary care unit of a tertiary care university hospital between September 2009 and August 2010 were tested for NGAL, IL-18 and CysC. Prospective demographic, clinical and laboratory data were evaluated as predictors of survival in this patient group. The most common cause of CCU admission was acute myocardial infarction (80%. According to Acute Kidney Injury Network criteria, 28.7% (43/150 of CCU patients had AKI of varying severity. Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.05 between patients with AKI versus those without AKI. For predicting AKI, serum CysC displayed an excellent areas under the receiver operating characteristic curve (AUROC (0.895 ± 0.031, p < 0.001. The overall 180-day survival rate was 88.7% (133/150. Multiple Cox logistic regression hazard analysis revealed that urinary NGAL, serum IL-18, Acute Physiology, Age and Chronic Health Evaluation II (APACHE II and sodium on CCU admission day one were independent risk factors for 6-month mortality. In terms of 6-month mortality, urinary NGAL had the best discriminatory power, the best Youden index, and the highest overall correctness of prediction. CONCLUSIONS: Our data showed that serum CysC has the best discriminative power for predicting AKI in CCU patients. However, urinary NGAL and serum IL-18 are associated with short-term mortality in these critically ill patients.

  15. Biomarkers of brain injury following an American football game: A pilot study.

    Science.gov (United States)

    Rogatzki, Matthew J; Soja, Scott E; McCabe, Colleen A; Breckenridge, Ryanne E; White, Jeffrey L; Baker, Julien S

    2016-09-01

    The goals of this study were to determine if the biomarkers of head injury, NSE and S100B, increased in serum following an American football game. Serum creatine kinase (CK) and cortisol levels were also measured to determine muscle damage and stress caused by the football game. NSE, S100B, CK, and cortisol were measured in the serum of 17 football players before and after a collegiate junior varsity football game. No head injuries were reported by the players, athletic training staff, or coaches yet both NSE (Pre-game: 7.0 μg•L-1 ± 2.2 versus Post-game: 13.1 μg•L-1 ± 7.0, P game: 0.013 μg•L-1 ± 0.012 versus Post-game: 0.069 μg•L-1 ± 0.036, P game: 90.5 U•L-1 ± 41.9 versus Post-game: 120.2 U•L-1 ± 62.7, P = 0.116) nor cortisol (Pre-game: 369.2 nmoles•L-1 ± 159.8 versus Post-game: 353.0 nmoles•L-1 ± 170.5, P = 0.349) increased significantly following the football game. There was little correlation found between S100B and body mass (R2 = 0.029) or CK (R2 = 0.352) levels. Although serum NSE and S100B increase as a result of playing in an American football game, the values are similar to or lower than levels found following competition in other contact and non-contact sports. Furthermore, the lack of correlation between S100B and body mass or CK indicates that S100B increases independent of body mass or muscle injury.

  16. An exploratory study of the effects of occupational exposure to physical demands on biomarkers of cartilage and muscle damage.

    Science.gov (United States)

    Christian, Marc; Nussbaum, Maury A

    2015-01-01

    Biomarkers of tissue damage, derived from tissues commonly injured as a result of occupational physical demands, may be of use for future prediction of work-related musculoskeletal disorders (WMSDs). This exploratory study assessed whether selected biomarkers are likely to be sensitive to the level of occupational physical demands. Twenty-four participants were recruited to form two groups, with relatively high and low levels of WMSD risk. Serum levels of Cartilage Oligomeric Matrix Protein (COMP), Interleukin-6 (IL6), and Creatine Kinase (CK)--which respectively indicate cartilage damage, muscle use, and muscle damage--were obtained,. Six blood samples were obtained before and after work on Monday, Wednesday, and Friday of one working week. Additionally, a self-report measure of risk factor exposure, the Hollmann Index, was used to, and did, confirm group differences in WMSD risk. COMP levels varied significantly over time, but not between groups. IL6 levels were greater in the high-risk group at all time points and varied significantly over time and between groups. CK levels did not vary significantly over time or between groups. IL6 successfully differentiated between the high and low risk groups, suggesting potential use in the occupational domain. Prospective studies are needed, though, to associate biomarker levels/changes with WMSD risk.

  17. Lysosomal membrane stability and metallothioneins in digestive gland of mussels (Mytilus galloprovincialis Lam.) as biomarkers in a field study

    Energy Technology Data Exchange (ETDEWEB)

    Petrovic, S.; Ozretic, B.; Krajnovic-Ozretic, M. [Ruder Boskovic Inst., Center for Marine Research, Rovinj (Croatia); Bobinac, D. [Rijeka Univ., Dept. of Anatomy, Rijeka (Croatia)

    2001-07-01

    The lysosomal membrane destabilisation and the metallothionein content in the digestive gland cells of mussels (Mytilus galloprovincialis Lam.), collected along the east coast of the North Adriatic (Istrian and Kvarnerine coast, Croatia), were examined over a period of four years (1996-1999). The lysosomal membrane stability, as a biomarker of general stress, showed that the membrane labilisation period in mussels from polluted, urban- and industrial-related areas was significantly decreased (p<0.05) when compared to mussels from control, clean sea water sites. In the harbour of Rijeka, the most contaminated site, the lysosomal membrane stability was reduced by more than 70% compared to the control. This method also proved to be a useful biomarker for detection of additional stress caused by short-term hypoxia that occurred once during this study inside the polluted and periodically quite eutrophic Pula Harbour. The concentration of metallothioneins in the mussel digestive gland, as a specific biomarker of exposure to heavy metals, did not reveal significant differences (p<0.05) between sites covered by this study. (Author)

  18. Independent Candidate Serum Protein Biomarkers of Response to Adalimumab and to Infliximab in Rheumatoid Arthritis: An Exploratory Study.

    Science.gov (United States)

    Ortea, Ignacio; Roschitzki, Bernd; López-Rodríguez, Rosario; Tomero, Eva G; Ovalles, Juan G; López-Longo, Javier; de la Torre, Inmaculada; González-Alvaro, Isidoro; Gómez-Reino, Juan J; González, Antonio

    2016-01-01

    Response to treatment of rheumatoid arthritis shows large inter-individual variability. This heterogeneity is observed with all the anti-rheumatic drugs, including the commonly used TNF inhibitors. It seems that drug-specific and target-specific factors lead individual patients to respond or not to a given drug, although this point has been challenged. The search of biomarkers distinguishing responders from non-responders has included shotgun proteomics of serum, as a previous study of response to infliximab, an anti-TNF antibody. Here, we have used the same study design and technology to search biomarkers of response to a different anti-TNF antibody, adalimumab, and we have compared the results obtained for the two anti-TNF drugs. Search of biomarkers of response to adalimumab included depletion of the most abundant serum proteins, 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) labeling, two-dimensional liquid chromatography fractionation and relative quantification with a hybrid Orbitrap mass spectrometer. With this approach, 264 proteins were identified in all the samples with at least 2 peptides and 95% confidence. Nine proteins showed differences between non-responders and responders (P treatment of rheumatoid arthritis and indicate that they are notably drug-specific.

  19. 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.

  20. Use of Arius thalassinus fish in a pollution biomonitoring study, applying combined oxidative stress, hematology, biochemical and histopathological biomarkers: A baseline field study.

    Science.gov (United States)

    Saleh, Yousef S; Marie, Mohamed-Assem S

    2016-05-15

    The present field study aimed to determine the extent of pollution in the Red Sea coast of Yemen Republic using a battery of biomarkers in sea catfish, Arius thalassinus, originating from a reference site in comparison with a polluted site. We reported the concentration of heavy metals in some vital fish organs and their effects on the morphological, hematological, biochemical and oxidative stress biomarkers accompanied by the examination of histopathological alterations. The obtained results showed clear signs of stress in fish from a polluted site. Linear correlation analysis exhibited that the biomarkers response could be linked to the detected metals bioaccumulation. In addition, principal component analysis showed a clear separation of sampling sites in two different assemblages. Semi-quantitative analysis for the observed histopathological lesions revealed that gills were the most affected organs with signs of severe alterations. This field investigation provides a baseline data on pollution status in this region.

  1. 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

    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...... 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...

  2. Biomarkers for neuromyelitis optica.

    Science.gov (United States)

    Chang, Kuo-Hsuan; Ro, Long-Sun; Lyu, Rong-Kuo; Chen, Chiung-Mei

    2015-02-02

    Neuromyelitis optica (NMO) is an acquired, heterogeneous inflammatory disorder, which is characterized by recurrent optic neuritis and longitudinally extensive spinal cord lesions. The discovery of the serum autoantibody marker, anti-aquaporin 4 (anti-AQP4) antibody, revolutionizes our understanding of pathogenesis of NMO. In addition to anti-AQP4 antibody, other biomarkers for NMO are also reported. These candidate biomarkers are particularly involved in T helper (Th)17 and astrocytic damages, which play a critical role in the development of NMO lesions. Among them, IL-6 in the peripheral blood is associated with anti-AQP4 antibody production. Glial fibrillary acidic protein (GFAP) in CSF demonstrates good correlations with clinical severity of NMO relapses. Detecting these useful biomarkers may be useful in the diagnosis and evaluation of disease activity of NMO. Development of compounds targeting these biomarkers may provide novel therapeutic strategies for NMO. This article will review the related biomarker studies in NMO and discuss the potential therapeutics targeting these biomarkers.

  3. Development of a multi-biomarker disease activity test for rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Michael Centola

    Full Text Available BACKGROUND: Disease activity measurement is a key component of rheumatoid arthritis (RA management. Biomarkers that capture the complex and heterogeneous biology of RA have the potential to complement clinical disease activity assessment. OBJECTIVES: To develop a multi-biomarker disease activity (MBDA test for rheumatoid arthritis. METHODS: Candidate serum protein biomarkers were selected from extensive literature screens, bioinformatics databases, mRNA expression and protein microarray data. Quantitative assays were identified and optimized for measuring candidate biomarkers in RA patient sera. Biomarkers with qualifying assays were prioritized in a series of studies based on their correlations to RA clinical disease activity (e.g. the Disease Activity Score 28-C-Reactive Protein [DAS28-CRP], a validated metric commonly used in clinical trials and their contributions to multivariate models. Prioritized biomarkers were used to train an algorithm to measure disease activity, assessed by correlation to DAS and area under the receiver operating characteristic curve for classification of low vs. moderate/high disease activity. The effect of comorbidities on the MBDA score was evaluated using linear models with adjustment for multiple hypothesis testing. RESULTS: 130 candidate biomarkers were tested in feasibility studies and 25 were selected for algorithm training. Multi-biomarker statistical models outperformed individual biomarkers at estimating disease activity. Biomarker-based scores were significantly correlated with DAS28-CRP and could discriminate patients with low vs. moderate/high clinical disease activity. Such scores were also able to track changes in DAS28-CRP and were significantly associated with both joint inflammation measured by ultrasound and damage progression measured by radiography. The final MBDA algorithm uses 12 biomarkers to generate an MBDA score between 1 and 100. No significant effects on the MBDA score were found for

  4. Combined heavy mineral and biomarker analysis in silt: a novel approach for provenance studies (Indus Fan, IODP Expedition 355)

    Science.gov (United States)

    Andò, Sergio; Bratenkov, Sophia; Hahn, Annette; George, Simon; Clift, Peter D.; Garzanti, Eduardo

    2016-04-01

    A high-resolution mineralogical study of Indus Fan turbiditic sediments cored during IODP Expedition 355 (Arabian Sea Monsoon) in the Laxmi Basin was carried out to investigate and quantify the different compositional signatures encoded in the sand, silt, and clay fractions. The turbidite deposits recovered at IODP Sites U1456 and U1457 in sedimentological Unit II were chosen as the best candidate for such a study. The integrated dataset presented here was obtained by coupling traditional and innovative bulk-sediment to single-grain analytical techniques, including bulk petrography, heavy-mineral and biomarker analyses on the same samples. Reliable quantitative results even in the medium to fine silt classes, which represent the dominant sediment sizes encountered in the recovered cores, were obtained by point-counting under the microscope, assisted by Micro-Raman spectroscopy (Andò et al., 2011; 2014). Preliminary data from the studied turbidites document rich and diverse heavy mineral assemblages in both the sand and silty-sand fractions. Heavy-mineral concentrations, as well as the number of mineral species, reach a maximum in sand and tend to decrease with grain size, becoming minimal in the clay fraction. Conversely, the biomarker analysis is generally focused on the finer sediment fractions and clay, where better preservation of biomarker compounds are obtained. The two approaches are thus complementary. Because biomarkers tend to be depleted in sand and heavy minerals in clay, the medium silt fraction represents the most suitable size window for the joint application of these two techniques. Comparing heavy-mineral assemblages with biomarkers allows us to evaluate both continental and marine inputs in turbidites and the hemipelagic deposits of the Indus Fan. This new methodological approach plays a key role in the identification of the effects of climate change on marine depositional environments and helps us to differentiate among the diverse Himalayan

  5. Poor replication validity of biomedical association studies reported by newspapers

    Science.gov (United States)

    Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists

  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. Protein Biomarkers Identify Patients Unlikely to Benefit from Primary Prevention ICDs: Findings from the PROSE-ICD Study

    Science.gov (United States)

    Cheng, Alan; Zhang, Yiyi; Blasco-Colmenares, Elena; Dalal, Darshan; Butcher, Barbara; Norgard, Sanaz; Eldadah, Zayd; Ellenbogen, Kenneth A.; Dickfeld, Timm; Spragg, David D.; Marine, Joseph E.; Guallar, Eliseo; Tomaselli, Gordon F.

    2015-01-01

    Background Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality but the benefits are heterogeneous. Current risk stratification based on left ventricular ejection fraction has limited discrimination power. We hypothesize that biomarkers for inflammation, neurohumoral activation and cardiac injury can predict appropriate shocks and all-cause mortality in patients with primary prevention ICDs. Methods and Results The Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSe-ICD) enrolled 1,189 patients with systolic heart failure who underwent ICD implantation for primary prevention of sudden cardiac death. The primary endpoint was an ICD shock for adjudicated ventricular tachyarrhythmia. The secondary endpoint was all-cause mortality. After a median follow-up of 4.0 years, 137 subjects experienced an appropriate ICD shock and 343 participants died (incidence rates of 3.2 and 5.8 per 100 person-years, respectively). In multivariable adjusted models, higher interleukin-6 (IL-6) levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, IL-6, tumor necrosis factor-α receptor II, pro-brain natriuretic peptide, and cardiac troponin T showed significant linear trends for increased risk of all-cause mortality across quartiles. A score combining these 5 biomarkers identified patients who were much more likely to die than to receive an appropriate shock from the ICD. Conclusions An increase in serum biomarkers of inflammation, neurohumoral activation and myocardial injury increased the risk for death but poorly predicted the likelihood of an ICD shock. These findings highlight the potential importance of serum-based biomarkers in identifying patients who are unlikely to benefit from primary prevention ICDs. PMID:25273351

  8. Characterization of artificial spherical particles for DEM validation studies

    Institute of Scientific and Technical Information of China (English)

    Ignazio Cavarretta; Catherine O'Sullivan; Erdin Ibraim; Martin Lings; Simon Hamlin; David Muir Wood

    2012-01-01

    This paper describes a study in which advanced particle-scale characterization was carried out on spherical particles that can be used in experimental tests to validate discrete element method (DEM) simulations,Two types of particle,alkaline and borosilicate glass heads,made from two different materials,were considered.The particle shape,stiffness,contact friction properties and surface roughness were measured.The influences of hardness and roughness on the mechanical response of the particles were carefully considered.Compared to the alkaline beads,the borosilicate beads were more spherical and more uniform in size,and they exhibited mechanical characteristics closer to natural quartz sand.While only two material types were studied,the work has the broader implication as a methodology for selecting particles suitable for use in DEM studies and the key parameters that should be considered in the selection process are highlighted.

  9. Assessing interpersonal aspects of schizoid personality disorder: preliminary validation studies.

    Science.gov (United States)

    Kosson, David S; Blackburn, Ronald; Byrnes, Katherine A; Park, Sohee; Logan, Caroline; Donnelly, John P

    2008-03-01

    In 2 studies, we examined the reliability and validity of an interpersonal measure of schizoid personality disorder (SZPD) based on nonverbal behaviors and interpersonal interactions occurring during interviews. A total of 556 male jail inmates in the United States participated in Study 1; 175 mentally disordered offenders in maximum security hospitals in the United Kingdom participated in Study 2. Across both samples, scores on the Interpersonal Measure of Schizoid Personality Disorder (IM-SZ) exhibited adequate reliability and patterns of correlations with other measures consistent with expectations. The scale displayed patterns of relatively specific correlations with interview and self-report measures of SZPD. In addition, the IM-SZ correlated in an expected manner with features of psychopathy and antisocial personality and with independent ratings of interpersonal behavior. We address implications for assessment of personality disorder.

  10. Geographic literacy perception scale (GLPS validity and reliability study

    Directory of Open Access Journals (Sweden)

    Yurdal Dikmenli

    2014-04-01

    Full Text Available Geographic literacy could be defined as the competence of turning understanding and comprehension of geographical knowledge into a skill because literacy consists of solving problems, reasoning, critical and creative thinking processes. Today, in order to impart literacy skills to individuals, teachers should first have these skills. It is important that teacher candidates should attain these skills before graduation. When these conditions are established, it will be easier for teacher candidates to be aware of their geographic literacy skills, bring these competences to a conscious level and contribute to students’ geographic literacy skills and processes in their professional lives. The main purpose of this study is to develop an attitude scale in order to specify teacher candidates’ geographic literacy perception levels. The study group of the research consisted of 473 teacher candidates. In order to detect the validity of the scale, exploratory factor analyses, item factor total correlations and item discriminations were conducted. In order to assess the reliability of the scale, the level of internal consistency and stability levels were calculated. The analyses provided evidence that the Geographic Literacy Perception Scale (GLPS is a valid and reliable scale that can be used in order to determine geographic literacy levels

  11. Use of wearable technology for performance assessment: a validation study.

    Science.gov (United States)

    Papi, Enrica; Osei-Kuffour, Denise; Chen, Yen-Ming A; McGregor, Alison H

    2015-07-01

    The prevalence of osteoarthritis is increasing globally but current compliance with rehabilitation remains poor. This study explores whether wearable sensors can be used to provide objective measures of performance with a view to using them as motivators to aid compliance to osteoarthritis rehabilitation. More specifically, the use of a novel attachable wearable sensor integrated into clothing and inertial measurement units located in two different positions, at the waist and thigh pocket, was investigated. Fourteen healthy volunteers were asked to complete exercises adapted from a knee osteoarthritis rehabilitation programme whilst wearing the three sensors including five times sit-to-stand test, treadmill walking at slow, preferred and fast speeds. The performances of the three sensors were validated against a motion capture system and an instrumented treadmill. The systems showed a high correlation (r(2) > 0.7) and agreement (mean difference range: -0.02-0.03 m, 0.005-0.68 s) with gold standards. The novel attachable wearable sensor was able to monitor exercise tasks as well as the inertial measurement units (ICC > 0.95). Results also suggested that a functional placement (e.g., situated in a pocket) is a valid position for performance monitoring. This study shows the potential use of wearable technologies for assessing subject performance during exercise and suggests functional solutions to enhance acceptance.

  12. Spectro-Fluor™ Technology for Reliable Detection of Proteins and Biomarkers of Disease: A Pioneered Research Study

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    Farid Menaa

    2014-09-01

    Full Text Available Quantitative and qualitative characterization of fluorinated molecules represents an important task. Fluorine-based medicinal chemistry is a fast-growing research area due to the positive impact of fluorine in drug discovery, and clinical and molecular imaging (e.g., magnetic resonance imaging, positron emission tomography. Common detection methods include fluorinated-based labelling using radioactive isotopes or fluorescent dyes. Nevertheless, these molecular imaging methods can be harmful for health due to the potential instability of fluorochromes and cytoxicity of radioisotopes. Therefore, these methods often require expensive precautionary measures. In this context, we have developed, validated and patented carbon-fluorine spectroscopy (CFS™, recently renamed Spectro-Fluor™ technology, which among a non-competitive family of in-house made devices called PLIRFA™ (Pulsed Laser Isochronic Raman and Fluorescence Apparatus™, allows reliable detection of Carbon-Fluorine (C-F bonds. C-F bonds are known to be stable and safe labels once incorporated to any type of molecules, cells, compounds or (nano- materials. In this pioneered research study, we used Spectro-Fluor™ to assess biomarkers. As a proof-of-principle experiment, we have established a three-step protocol intended to rapid protein detection, which simply consisted of: (i incorporating a sufficient concentration of an aromatic amino-acid (fluorinated versus non-fluorinated into cultured cells; (ii simultaneously isolating the fluorinated protein of interest and the non-fluorinated form of the protein (control by immune-precipitation; (iii comparatively analyzing the respective spectrum obtained for the two protein forms by Spectro-Fluor™. Thereby, we were able to differentiate, from colon cancer cells HCT-116, the fluorinated and non-fluorinated forms of p21, a key transcriptional factor and downstream target of p53, the so-called “guardian of the genome”. Taken together

  13. Spectro-Fluor™ Technology for Reliable Detection of Proteins and Biomarkers of Disease: A Pioneered Research Study.

    Science.gov (United States)

    Menaa, Farid; Menaa, Bouzid; Sharts, Olga N

    2014-01-01

    Quantitative and qualitative characterization of fluorinated molecules represents an important task. Fluorine-based medicinal chemistry is a fast-growing research area due to the positive impact of fluorine in drug discovery, and clinical and molecular imaging (e.g., magnetic resonance imaging, positron emission tomography). Common detection methods include fluorinated-based labelling using radioactive isotopes or fluorescent dyes. Nevertheless, these molecular imaging methods can be harmful for health due to the potential instability of fluorochromes and cytoxicity of radioisotopes. Therefore, these methods often require expensive precautionary measures. In this context, we have developed, validated and patented carbon-fluorine spectroscopy (CFS™), recently renamed Spectro-Fluor™ technology, which among a non-competitive family of in-house made devices called PLIRFA™ (Pulsed Laser Isochronic Raman and Fluorescence Apparatus™), allows reliable detection of Carbon-Fluorine (C-F) bonds. C-F bonds are known to be stable and safe labels once incorporated to any type of molecules, cells, compounds or (nano-) materials. In this pioneered research study, we used Spectro-Fluor™ to assess biomarkers. As a proof-of-principle experiment, we have established a three-step protocol intended to rapid protein detection, which simply consisted of: (i) incorporating a sufficient concentration of an aromatic amino-acid (fluorinated versus non-fluorinated) into cultured cells; (ii) simultaneously isolating the fluorinated protein of interest and the non-fluorinated form of the protein (control) by immune-precipitation; (iii) comparatively analyzing the respective spectrum obtained for the two protein forms by Spectro-Fluor™. Thereby, we were able to differentiate, from colon cancer cells HCT-116, the fluorinated and non-fluorinated forms of p21, a key transcriptional factor and downstream target of p53, the so-called "guardian of the genome". Taken together, our data again

  14. Early diagnosis of complex diseases by molecular biomarkers, network biomarkers, and dynamical network biomarkers.

    Science.gov (United States)

    Liu, Rui; Wang, Xiangdong; Aihara, Kazuyuki; Chen, Luonan

    2014-05-01

    Many studies have been carried out for early diagnosis of complex diseases by finding accurate and robust biomarkers specific to respective diseases. In particular, recent rapid advance of high-throughput technologies provides unprecedented rich information to characterize various disease genotypes and phenotypes in a global and also dynamical manner, which significantly accelerates the study of biomarkers from both theoretical and clinical perspectives. Traditionally, molecular biomarkers that distinguish disease samples from normal samples are widely adopted in clinical practices due to their ease of data measurement. However, many of them suffer from low coverage and high false-positive rates or high false-negative rates, which seriously limit their further clinical applications. To overcome those difficulties, network biomarkers (or module biomarkers) attract much attention and also achieve better performance because a network (or subnetwork) is considered to be a more robust form to characterize diseases than individual molecules. But, both molecular biomarkers and network biomarkers mainly distinguish disease samples from normal samples, and they generally cannot ensure to identify predisease samples due to their static nature, thereby lacking ability to early diagnosis. Based on nonlinear dynamical theory and complex network theory, a new concept of dynamical network biomarkers (DNBs, or a dynamical network of biomarkers) has been developed, which is different from traditional static approaches, and the DNB is able to distinguish a predisease state from normal and disease states by even a small number of samples, and therefore has great potential to achieve "real" early diagnosis of complex diseases. In this paper, we comprehensively review the recent advances and developments on molecular biomarkers, network biomarkers, and DNBs in particular, focusing on the biomarkers for early diagnosis of complex diseases considering a small number of samples and high

  15. The Process Chain for Peptidomic Biomarker Discovery

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    Michael Schrader

    2006-01-01

    Full Text Available Over the last few years the interest in diagnostic markers for specific diseases has increased continuously. It is expected that they not only improve a patient's medical treatment but also contribute to accelerating the process of drug development. This demand for new biomarkers is caused by a lack of specific and sensitive diagnosis in many diseases. Moreover, diseases usually occur in different types or stages which may need different diagnostic and therapeutic measures. Their differentiation has to be considered in clinical studies as well. Therefore, it is important to translate a macroscopic pathological or physiological finding into a microscopic view of molecular processes and vice versa, though it is a difficult and tedious task. Peptides play a central role in many physiological processes and are of importance in several areas of drug research. Exploration of endogenous peptides in biologically relevant sources may directly lead to new drug substances, serve as key information on a new target and can as well result in relevant biomarker candidates. A comprehensive analysis of peptides and small proteins of a biological system corresponding to the respective genomic information (peptidomics®methods was a missing link in proteomics. A new peptidomic technology platform addressing peptides was recently presented, developed by adaptation of the striving proteomic technologies. Here, concepts of using peptidomics technologies for biomarker discovery are presented and illustrated with examples. It is discussed how the biological hypothesis and sample quality determine the result of the study. A detailed study design, appropriate choice and application of technology as well as thorough data interpretation can lead to significant results which have to be interpreted in the context of the underlying disease. The identified biomarker candidates will be characterised in validation studies before use. This approach for discovery of peptide

  16. Functional MRI and CT biomarkers in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Winfield, J.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom); Institute of Cancer Research and Royal Marsden Hospital, MRI Unit, Sutton (United Kingdom); Payne, G.S.; DeSouza, N.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom)

    2015-04-01

    Imaging biomarkers derived from MRI or CT describe functional properties of tumours and normal tissues. They are finding increasing numbers of applications in diagnosis, monitoring of response to treatment and assessment of progression or recurrence. Imaging biomarkers also provide scope for assessment of heterogeneity within and between lesions. A wide variety of functional parameters have been investigated for use as biomarkers in oncology. Some imaging techniques are used routinely in clinical applications while others are currently restricted to clinical trials or preclinical studies. Apparent diffusion coefficient, magnetization transfer ratio and native T{sub 1} relaxation time provide information about structure and organization of tissues. Vascular properties may be described using parameters derived from dynamic contrast-enhanced MRI, dynamic contrast-enhanced CT, transverse relaxation rate (R{sub 2}*), vessel size index and relative blood volume, while magnetic resonance spectroscopy may be used to probe the metabolic profile of tumours. This review describes the mechanisms of contrast underpinning each technique and the technical requirements for robust and reproducible imaging. The current status of each biomarker is described in terms of its validation, qualification and clinical applications, followed by a discussion of the current limitations and future perspectives. (orig.)

  17. Checklist for the qualitative evaluation of clinical studies with particular focus on external validity and model validity

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    Vollmar Horst C

    2006-12-01

    Full Text Available Abstract Background It is often stated that external validity is not sufficiently considered in the assessment of clinical studies. Although tools for its evaluation have been established, there is a lack of awareness of their significance and application. In this article, a comprehensive checklist is presented addressing these relevant criteria. Methods The checklist was developed by listing the most commonly used assessment criteria for clinical studies. Additionally, specific lists for individual applications were included. The categories of biases of internal validity (selection, performance, attrition and detection bias correspond to structural, treatment-related and observational differences between the test and control groups. Analogously, we have extended these categories to address external validity and model validity, regarding similarity between the study population/conditions and the general population/conditions related to structure, treatment and observation. Results A checklist is presented, in which the evaluation criteria concerning external validity and model validity are systemised and transformed into a questionnaire format. Conclusion The checklist presented in this article can be applied to both planning and evaluating of clinical studies. We encourage the prospective user to modify the checklists according to the respective application and research question. The higher expenditure needed for the evaluation of clinical studies in systematic reviews is justified, particularly in the light of the influential nature of their conclusions on therapeutic decisions and the creation of clinical guidelines.

  18. [French validation study of the levels of emotional awareness scale].

    Science.gov (United States)

    Bydlowski, S; Corcos, M; Paterniti, S; Guilbaud, O; Jeammet, P; Consoli, S M

    2002-01-01

    According to a thesis based on the idea of an influence of cognitions in the structuring of internal reality, emotional awareness, ie the capacity of representing your own emotional experience and that of others, is a cognitive process that goes into maturation. Defining this concept, Lane and Schwartz present a cognitivo-developmental model in five stages of the processes of symbolization, accounting for the differences in levels of emotional awareness observed in individuals. The organization of these cognitive processes would thus be structured in well differentiated stages, in which the development of the emotions would be inseparable from the development of ego and of the relation to others. These authors focus on the capacity of representing in a conscious way the emotional experience and consider that verbal representations used to describe the contents of what is experience constitute a good reflection of the organization structural of the emotional awareness. Therefore, they worked out an instrument of evaluation: the Levels of Emotional Awareness Scale (LEAS), which measures the capacity to describe your own emotional experience and the one you allow to others, in an emotional situation. The system of quotation of this scale is based on the analysis of the verbal contents of the provided answers, in direct reference to the authors' theory of the levels of differentiation and integration of the emotional experience. It is therefore an empirical measurement which is centered specifically on the structural organization of the emotional experience. The various studies of validation of this instrument show that it presents solid metrological properties. This work presents the validation of the French version of Lane and Schwartz's LEAS. Validity and fidelity were studied in a group of 121 healthy subjects. This setting is part of a larger clinical evaluation, also including a collection of socio-demographic and clinical data, and other instruments of self

  19. Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

    OpenAIRE

    Yingrong Chen; Zhihong Ma; Lishan Min; Hongwei Li; Bin Wang; Jing Zhong; Licheng Dai

    2015-01-01

    Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top...

  20. Biopsable neural tissues: toward new biomarkers for Parkinson’s disease?

    Directory of Open Access Journals (Sweden)

    Thibaud Lebouvier

    2010-09-01

    Full Text Available Biomarkers for Parkinson’s disease (PD are mainly intended for the early diagnosis of the disease and to monitor its progression, two aspects insufficiently covered by clinical evaluation. In the last 20 years, the search for biomarkers has been supported by technological advances in the fields of molecular genetics and neuroimaging. Nevertheless, no fully validated biomarker is yet available, and there is still a need for biomarkers that will complement those already available. Development of biomarkers for PD has been hampered by the fact that the core pathology lies in the brainstem, hidden from direct study in living patients. In this context, the recent observations that clearly demonstrated the presence of PD pathology in peripheral neural tissues provide new opportunities to develop original histopathological markers of the disease. Some of these peripheral tissues, especially the enteric nervous system, by being assessable using routine biopsies, could represent a window to assess in vivo the neuropathological processes occurring in PD.

  1. Lamb wave Shearwave dispersion ultrasound Vibrometry (SDUV) validation study.

    Science.gov (United States)

    Nenadic, Ivan; Urban, Matthew W; Mitchell, Scott A; Greenleaf, James F

    2010-01-01

    Our group has been investigating the use of Shearwave Dispersion Ultrasound Vibrometry (SDUV) for quantifying viscoelasticity of the myocardium. The primary aim of this study is the design and testing of viscoelastic materials suitable for validation of the Lamb wave model in the heart. The Lamb wave SDUV method was used to measure shear wave velocity dispersion of gelatin and urethane rubber plates in the range 40-500 Hz and estimate the material properties. A finite element model (FEM) of a viscoelastic plate submerged in water was used to study the appropriateness of the Lamb wave dispersion equations. An embedded sphere method was used as an independent measurement of viscoelasticity. The FEM wave velocity dispersion data were in excellent agreement with the theoretical predictions. Elasticity and viscosity of urethane and gelatin obtained using the Lamb wave SDUV and embedded sphere methods agree within one standard deviation.

  2. SPORT FAN MOTIVATION QUESTIONNAIRE: A STUDY OF VALIDITY AND RELIABILITY

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    Muhammed Emin KAFKAS

    2012-04-01

    Full Text Available The purpose of this research, Yousof Al-Thibiti (2004 Fan Motivational scale was developed by Turkish adapts and scales to analyze the validity and reliability. The study group was composed that Inonu University studying at different faculty of education between the age of 17-31 494’ü (%54 women and 421’i (%46 male students. Firstly of linguistic equivalence of the scale were examined. Secondly after linguistic equivalence was performed reliability analysis. The total scale internal consistency coefficients for sizes .85 and subscale range of .70-.78, the re-test reliability coefficients were between .79-.89. at the same time, exploratory factor analysis and confirmatory factor analysis is carried out with the scale and found to comply with the data. As a result of scale to measure the status of individuals to participate in sporting activities was found to have an appropriate structure.

  3. The Fast Scattering Code (FSC): Validation Studies and Program Guidelines

    Science.gov (United States)

    Tinetti, Ana F.; Dunn, Mark H.

    2011-01-01

    The Fast Scattering Code (FSC) is a frequency domain noise prediction program developed at the NASA Langley Research Center (LaRC) to simulate the acoustic field produced by the interaction of known, time harmonic incident sound with bodies of arbitrary shape and surface impedance immersed in a potential flow. The code uses the equivalent source method (ESM) to solve an exterior 3-D Helmholtz boundary value problem (BVP) by expanding the scattered acoustic pressure field into a series of point sources distributed on a fictitious surface placed inside the actual scatterer. This work provides additional code validation studies and illustrates the range of code parameters that produce accurate results with minimal computational costs. Systematic noise prediction studies are presented in which monopole generated incident sound is scattered by simple geometric shapes - spheres (acoustically hard and soft surfaces), oblate spheroids, flat disk, and flat plates with various edge topologies. Comparisons between FSC simulations and analytical results and experimental data are presented.

  4. A Pilot Study to Evaluate Renal Hemodynamics in Cirrhosis by Simultaneous Glomerular Filtration Rate, Renal Plasma Flow, Renal Resistive Indices and Biomarkers Measurements

    Science.gov (United States)

    Mindikoglu, Ayse L.; Dowling, Thomas C.; Wong-You-Cheong, Jade J.; Christenson, Robert H.; Magder, Laurence S.; Hutson, William R.; Seliger, Stephen L.; Weir, Matthew R.

    2014-01-01

    Background Renal hemodynamic measurements are complicated to perform in patients with cirrhosis; yet they provide the best measure of risk to predict hepatorenal syndrome (HRS). Currently, there are no established biomarkers of altered renal hemodynamics in cirrhosis validated by measured renal hemodynamics. Methods In this pilot study, simultaneous measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), renal resistive indices and biomarkers were performed to evaluate renal hemodynamic alterations in 10 patients with cirrhosis (3 patients without ascites, 5 with diuretic sensitive and 2 diuretic refractory ascites). Results Patients with diuretic refractory ascites had the lowest mean GFR (36.5 ml/min/1.73m2) and RPF (133.6 ml/min/1.73m2) when compared to those without ascites (GFR=82.9 ml/min/1.73m2, RPF=229.9 ml/min/1.73m2) and with diuretic-sensitive ascites (GFR=82.3 ml/min/1.73m2, RPF=344.1 ml/min/1.73m2). A higher mean filtration fraction (FF= GFR/RPF=0.36) was noted among those without ascites compared to those with ascites. Higher FF in patients without ascites is most likely secondary to the vasoconstriction in the efferent glomerular arterioles (normal FF≃0.20). In general, renal resistive indices were inversely related to FF. While patients with ascites had lower FF and higher right kidney main and arcuate artery resistive indices, those without ascites had higher FF and lower right kidney main and arcuate artery resistive indices. While cystatin C and beta-2 microglobulin performed better compared to Cr in estimating RPF; beta-trace protein, beta-2 microglobulin, SDMA, and (SDMA+ADMA) performed better in estimating right kidney arcuate artery resistive index. Conclusion The results of this pilot study showed that identification of non-invasive biomarkers of reduced RPF and increased renal resistive indices can identify cirrhotics at risk for HRS at a stage more amenable to therapeutic intervention, and reduce mortality from kidney

  5. Trace elements as tumor biomarkers and prognostic factors in breast cancer: a study through energy dispersive x-ray fluorescence

    Directory of Open Access Journals (Sweden)

    Silva Marina P

    2012-07-01

    Full Text Available Abstract Background The application and better understanding of traditional and new breast tumor biomarkers and prognostic factors are increasing due to the fact that they are able to identify individuals at high risk of breast cancer, who may benefit from preventive interventions. Also, biomarkers can make possible for physicians to design an individualized treatment for each patient. Previous studies showed that trace elements (TEs determined by X-Ray Fluorescence (XRF techniques are found in significantly higher concentrations in neoplastic breast tissues (malignant and benign when compared with normal tissues. The aim of this work was to evaluate the potential of TEs, determined by the use of the Energy Dispersive X-Ray Fluorescence (EDXRF technique, as biomarkers and prognostic factors in breast cancer. Methods By using EDXRF, we determined Ca, Fe, Cu, and Zn trace elements concentrations in 106 samples of normal and breast cancer tissues. Cut-off values for each TE were determined through Receiver Operating Characteristic (ROC analysis from the TEs distributions. These values were used to set the positive or negative expression. This expression was subsequently correlated with clinical prognostic factors through Fisher’s exact test and chi-square test. Kaplan Meier survival curves were also evaluated to assess the effect of the expression of TEs in the overall patient survival. Results Concentrations of TEs are higher in neoplastic tissues (malignant and benign when compared with normal tissues. Results from ROC analysis showed that TEs can be considered a tumor biomarker because, after establishing a cut-off value, it was possible to classify different tissues as normal or neoplastic, as well as different types of cancer. The expression of TEs was found statistically correlated with age and menstrual status. The survival curves estimated by the Kaplan-Meier method showed that patients with positive expression for Cu presented a poor

  6. Critical analysis of soil invertebrate biomarkers: a field case study in Avonmouth, UK.

    Science.gov (United States)

    Weeks, Jason M; Spurgeon, David J; Svendsen, Claus; Hankard, Peter K; Kammenga, Jan E; Dallinger, Reinhard; Köhler, Heinz-R; Simonsen, Vibeke; Scott-Fordsmand, Janeck

    2004-11-01

    During the period 1996-1999 a joint field research programme (BIOPRINT-II) funded by the European Union was undertaken. The main objective of this project was the deployment of biochemical fingerprint techniques of soil invertebrate biomarkers for assessing the exposure and effect of toxicants on soil invertebrates in the field. The aim was to apply these techniques in the field focusing on a a chronically polluted field near a lead and zinc smelter in Avonmouth (UK). Therefore six sites were selected from which organisms were either sampled or transplanted to or from the laboratory. The project has provided a unique opportunity to apply a series of biological test methodologies in order to determine the hazard posed to soil sustainability and by inference soil biodiversity and function. This work has attempted to understand the linkage between effects measured at the molecular or cellular level and relate these to changes at higher levels of biological organisation. Here we evaluated the links between biomarkers and soil function parameters. The paper aims to summarize and explore the necessary caveats that must be understood before soil biomarker test systems may be used to strengthen the risk assessment process.

  7. Paleoenvironmental assessment of recent environmental changes in Florida Bay, USA: A biomarker based study

    Science.gov (United States)

    Xu, Yunping; Holmes, Charles W.; Jaffé, Rudolf

    2007-06-01

    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 C 25/C 27n-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 (C 20 HBIs, C 25 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 C 25 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.

  8. Dietary biomarkers: advances, limitations and future directions

    Directory of Open Access Journals (Sweden)

    Hedrick Valisa E

    2012-12-01

    Full Text Available Abstract The subjective nature of self-reported dietary intake assessment methods presents numerous challenges to obtaining accurate dietary intake and nutritional status. This limitation can be overcome by the use of dietary biomarkers, which are able to objectively assess dietary consumption (or exposure without the bias of self-reported dietary intake errors. The need for dietary biomarkers was addressed by the Institute of Medicine, who recognized the lack of nutritional biomarkers as a knowledge gap requiring future research. The purpose of this article is to review existing literature on currently available dietary biomarkers, including novel biomarkers of specific foods and dietary components, and assess the validity, reliability and sensitivity of the markers. This review revealed several biomarkers in need of additional validation research; research is also needed to produce sensitive, specific, cost-effective and noninvasive dietary biomarkers. The emerging field of metabolomics may help to advance the development of food/nutrient biomarkers, yet advances in food metabolome databases are needed. The availability of biomarkers that estimate intake of specific foods and dietary components could greatly enhance nutritional research targeting compliance to national recommendations as well as direct associations with disease outcomes. More research is necessary to refine existing biomarkers by accounting for confounding factors, to establish new indicators of specific food intake, and to develop techniques that are cost-effective, noninvasive, rapid and accurate measures of nutritional status.

  9. Dietary biomarkers: advances, limitations and future directions.

    Science.gov (United States)

    Hedrick, Valisa E; Dietrich, Andrea M; Estabrooks, Paul A; Savla, Jyoti; Serrano, Elena; Davy, Brenda M

    2012-12-14

    The subjective nature of self-reported dietary intake assessment methods presents numerous challenges to obtaining accurate dietary intake and nutritional status. This limitation can be overcome by the use of dietary biomarkers, which are able to objectively assess dietary consumption (or exposure) without the bias of self-reported dietary intake errors. The need for dietary biomarkers was addressed by the Institute of Medicine, who recognized the lack of nutritional biomarkers as a knowledge gap requiring future research. The purpose of this article is to review existing literature on currently available dietary biomarkers, including novel biomarkers of specific foods and dietary components, and assess the validity, reliability and sensitivity of the markers. This review revealed several biomarkers in need of additional validation research; research is also needed to produce sensitive, specific, cost-effective and noninvasive dietary biomarkers. The emerging field of metabolomics may help to advance the development of food/nutrient biomarkers, yet advances in food metabolome databases are needed. The availability of biomarkers that estimate intake of specific foods and dietary components could greatly enhance nutritional research targeting compliance to national recommendations as well as direct associations with disease outcomes. More research is necessary to refine existing biomarkers by accounting for confounding factors, to establish new indicators of specific food intake, and to develop techniques that are cost-effective, noninvasive, rapid and accurate measures of nutritional status.

  10. A validation study of a stochastic model of human interaction

    Science.gov (United States)

    Burchfield, Mitchel Talmadge

    The purpose of this dissertation is to validate a stochastic model of human interactions which is part of a developmentalism paradigm. Incorporating elements of ancient and contemporary philosophy and science, developmentalism defines human development as a progression of increasing competence and utilizes compatible theories of developmental psychology, cognitive psychology, educational psychology, social psychology, curriculum development, neurology, psychophysics, and physics. To validate a stochastic model of human interactions, the study addressed four research questions: (a) Does attitude vary over time? (b) What are the distributional assumptions underlying attitudes? (c) Does the stochastic model, {-}N{intlimitssbsp{-infty}{infty}}varphi(chi,tau)\\ Psi(tau)dtau, have utility for the study of attitudinal distributions and dynamics? (d) Are the Maxwell-Boltzmann, Fermi-Dirac, and Bose-Einstein theories applicable to human groups? Approximately 25,000 attitude observations were made using the Semantic Differential Scale. Positions of individuals varied over time and the logistic model predicted observed distributions with correlations between 0.98 and 1.0, with estimated standard errors significantly less than the magnitudes of the parameters. The results bring into question the applicability of Fisherian research designs (Fisher, 1922, 1928, 1938) for behavioral research based on the apparent failure of two fundamental assumptions-the noninteractive nature of the objects being studied and normal distribution of attributes. The findings indicate that individual belief structures are representable in terms of a psychological space which has the same or similar properties as physical space. The psychological space not only has dimension, but individuals interact by force equations similar to those described in theoretical physics models. Nonlinear regression techniques were used to estimate Fermi-Dirac parameters from the data. The model explained a high degree

  11. Metallomics study in CSF for putative biomarkers to predict cerebral vasospasm.

    Science.gov (United States)

    Zhang, Yaofang; Clark, Joseph F; Pyne-Geithman, Gail; Caruso, Joseph

    2010-09-01

    Cerebral vasospasm (CV) refers to physical narrowing of brain cerebral arteries due to over-contraction of the arterial wall, which often arises following a subarachnoid hemorrhage (SAH). CV is frequently associated with poorer outcomes in those patients. Between the ictus of SAH and its CV complication, there is a 3-7 days delay, which provides a time window to predict and possibly prevent the onset CV. Since the precise pathomechanism of CV is still unclear and approaches for predicting it are inefficient, more effective ways of predicting CV need to be developed. As a protective nourishing fluid flows through the subarachnoid space, cerebrospinal fluid (CSF) closely relates to the health states of the central nervous system (CNS). Analysis of CSF can provide invaluable information to diagnose, treat and prevent diseases of the CNS because of its relatively direct representation of events in the brain. Therefore, we assume that the components in CSF and their alterations may reflect the state of aneurismal SAH and the development of vasospasm. In this study, three types of CSF from healthy control, and patients who suffered SAH and its complication, CV, were investigated via two-dimensional separations in combination with elemental and molecular mass spectrometry detection for the identification of elemental species. Size exclusion chromatography (SEC) was initially used with selective metal detection by inductively coupled plasma mass spectrometry (ICPMS) for characterizing size distribution of metal species. Various molecular distribution patterns were exhibited at different metal detection points (Fe, Ni, Cu, Zn and Pb). Further identification of possible metallopeptides and metalloprotein in tryptic digested fractions from the three sample types were made via reverse phase (RP)-Chip and electrospray mass spectrometry (MS) in combination with the Spectrum Mill data base search engine accessing appropriate data bases. Comparisons were generated to show

  12. 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.

  13. Human Genotoxic Study Carried Out Two Years after Oil Exposure during the Clean-up Activities Using Two Different Biomarkers

    Directory of Open Access Journals (Sweden)

    Gloria Biern

    2015-11-01

    Full Text Available Micronuclei, comet and chromosome alterations assays are the most widely used biomarkers for determining the genotoxic damage in a population exposed to genotoxic chemicals. While chromosome alterations are an excellent biomarker to detect short- and long-term genotoxic effects, the comet assay only measures early biological effects, and furthermore it is unknown whether nuclear abnormalies, such as those measured in the micronucleus test, remain detectable long-term after an acute exposure. In our previous study, an increase in structural chromosome alterations in fishermen involved in the clean-up of the Prestige oil spill, two years after acute exposure, was detected. The aim of this study is to investigate whether, in lymphocytes from peripheral blood, the nuclear abnormalies (micronucleus, nucleoplasmic bridges and nuclear buds have a similar sensitivity to the chromosome damage analysis for genotoxic detection two years after oil exposure in the same non-smoker individuals and in the same peripheral blood extraction. No significant differences in nuclear abnormalies frequencies between exposed and non-exposed individuals were found (p > 0.05. However, chromosome damage, in the same individuals, was higher in exposed vs. non-exposed individuals, especially for chromosome lesions (p < 0.05. These findings, despite the small sample size, suggest that nuclear abnormalities are probably less-successful biomarkers than are chromosome alterations to evaluate genotoxic effects two or more years after an exposure to oil. Due to the great advantage of micronucleus automatic determination, which allows for a rapid study of hundreds of individuals exposed to genotoxic chemical exposure, further studies are needed to confirm whether this assay is or is not useful in long-term genotoxic studies after the toxic agent is no longer present.

  14. Improving tuberculosis diagnostics with biomarkers

    Directory of Open Access Journals (Sweden)

    Shu CC

    2015-05-01

    Full Text Available Chin-Chung Shu,1,2 Jann-Yuan Wang,2 Li-Na Lee,2,3 Chong-Jen Yu,2 Kwen-Tay Luh3 1Department of Traumatology, 2Department of Internal Medicine, 3Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan Abstract: Although many laboratory methods have been developed to expedite the diagnosis of active tuberculosis (TB and Mycobacterium tuberculosis (Mtb infection, delays in diagnosis remain a major problem in clinical practice. Biomarkers may contribute favorably or unfavorably to TB diagnosis in a clinical suspect TB case with inconclusive diagnostic findings. A good understanding of the effectiveness and practical limitations of these biomarkers is important to improve diagnosis. This review summarizes currently used biomarkers, mainly as validation, and focuses on latent TB infection, active pulmonary TB, and tuberculous pleural effusion. Keywords: tuberculosis, biomarker, diagnosis, latent tuberculosis infection, pleural effusion 

  15. Validation of the MINI (DSM IV Tool for the Assessment of Alcohol Dependence among Young People in Northern Tanzania Using the Alcohol Biomarker Phosphatidylethanol (PEth

    Directory of Open Access Journals (Sweden)

    Joel M. Francis

    2015-10-01

    Full Text Available The alcohol dependence section of the Mini International Neuropsychiatric Interview questionnaire (MINI has not been evaluated in young Africans. We applied the MINI in a cross-sectional study of 202 alcohol users from northern-Tanzania, aged 18–24 years (103 male casual workers and 99 students, and validated it against phophatidylethanol (PEth at a cut-off suggesting heavy chronic alcohol use (≥0.30 µmol/L. Blood was assayed for PEth (16:0/18:1-subform by liquid chromatography-tandem mass spectrometry. The MINI dependence criteria (≥3 positive responses were met by 39% participants although their PEth levels were low. Contrary, many young people with high PEth levels were not classified as dependent. The sensitivity of the MINI ranged from 0% to 69% (female students and male workers, respectively and specificity from 52% to 85% (workers and female students, respectively. The highest AUROC (0.68 occurred with a cut-off of ≥4 positive responses. A modified MINI with three affirmative responses to five questions increased specificity to 92%–97%; however, sensitivity remained low. The performance of the MINI in detecting dependence among young people from northern-Tanzania is unsatisfactory. Specificity was improved using a modified version but sensitivity remained low. An accurate tool for the diagnosis of alcohol dependence is needed for epidemiological and clinical purposes.

  16. Imaging Biomarkers or Biomarker Imaging?

    Directory of Open Access Journals (Sweden)

    Markus Mitterhauser

    2014-06-01

    Full Text Available Since biomarker imaging is traditionally understood as imaging of molecular probes, we highly recommend to avoid any confusion with the previously defined term “imaging biomarkers” and, therefore, only use “molecular probe imaging (MPI” in that context. Molecular probes (MPs comprise all kinds of molecules administered to an organism which inherently carry a signalling moiety. This review highlights the basic concepts and differences of molecular probe imaging using specific biomarkers. In particular, PET radiopharmaceuticals are discussed in more detail. Specific radiochemical and radiopharmacological aspects as well as some legal issues are presented.

  17. 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.

    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

  18. 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

  19. Statistical Analysis and validation

    NARCIS (Netherlands)

    Hoefsloot, H.C.J.; Horvatovich, P.; Bischoff, R.

    2013-01-01

    In this chapter guidelines are given for the selection of a few biomarker candidates from a large number of compounds with a relative low number of samples. The main concepts concerning the statistical validation of the search for biomarkers are discussed. These complicated methods and concepts are

  20. Methylated genes as new cancer biomarkers.

    LENUS (Irish Health Repository)

    Duffy, M J

    2012-02-01

    Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.

  1. Validation of Heat Shock Protein 70 as a Tumor-Specific Biomarker for Monitoring the Outcome of Radiation Therapy in Tumor Mouse Models

    Energy Technology Data Exchange (ETDEWEB)

    Bayer, Christine; Liebhardt, Michael E.; Schmid, Thomas E. [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Trajkovic-Arsic, Marija [II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Hube, Kathrin; Specht, Hanno M. [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Schilling, Daniela [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Clinical Kooperation Group, Innate Immunity in Tumor Biology, HelmholtzZentrum München, Munich (Germany); Gehrmann, Mathias; Stangl, Stefan [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Siveke, Jens T. [II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Wilkens, Jan J. [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Multhoff, Gabriele, E-mail: Gabriele.multhoff@lrz.tum.de [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Clinical Kooperation Group, Innate Immunity in Tumor Biology, HelmholtzZentrum München, Munich (Germany)

    2014-03-01

    Purpose: Tumor cells, in contrast to normal cells, frequently overexpress heat shock protein 70 (Hsp70) in the cytosol, present it on their cell surface, and actively release it. Therefore, soluble Hsp70 (sHsp70) was investigated as a potential tumor biomarker for monitoring the outcome of radiation therapy. Methods and Materials: Plasma from mice bearing membrane Hsp70 (mHsp70)-positive FaDu human squamous cell carcinoma of the head and neck and spontaneous pancreatic ductal adenocarcinoma (PDAC) was investigated. A cohort of mice with FaDu tumors (0.32 cm{sup 3}) was irradiated with 30 Gy, and plasma was collected 24 hours after irradiation, after the tumors had shrunk to 50% of their starting volume and after complete remission. sHsp70 levels in the plasma were quantified by enzyme-linked immunosorbent assay. Results: sHsp70 levels were significantly higher in the blood of tumor-bearing mice than that of control animals. A correlation between increasing sHsp70 plasma levels and tumor volume in the range of 0.01 cm{sup 3} to 0.66 cm{sup 3} was observed. Radiation-induced regression of the tumors was associated with significantly decreased sHsp70 levels, which returned to the level of control animals after complete remission. Conclusion: We propose sHsp70 as an innovative biomarker for detecting tumors and for monitoring the clinical outcome of radiation therapy in cancer patients.

  2. Analytical Aspects of the Implementation of Biomarkers in Clinical Transplantation.

    Science.gov (United States)

    Shipkova, Maria; López, Olga Millán; Picard, Nicolas; Noceti, Ofelia; Sommerer, Claudia; Christians, Uwe; Wieland, Eberhard

    2016-04-01

    In response to the urgent need for new reliable biomarkers to complement the guidance of the immunosuppressive therapy, a huge number of biomarker candidates to be implemented in clinical practice have been introduced to the transplant community. This includes a diverse range of molecules with very different molecular weights, chemical and physical properties, ex vivo stabilities, in vivo kinetic behaviors, and levels of similarity to other molecules, etc. In addition, a large body of different analytical techniques and assay protocols can be used to measure biomarkers. Sometimes, a complex software-based data evaluation is a prerequisite for appropriate interpretation of the results and for their reporting. Although some analytical procedures are of great value for research purposes, they may be too complex for implementation in a clinical setting. Whereas the proof of "fitness for purpose" is appropriate for validation of biomarker assays used in exploratory drug development studies, a higher level of analytical validation must be achieved and eventually advanced analytical performance might be necessary before diagnostic application in transplantation medicine. A high level of consistency of results between laboratories and between methods (if applicable) should be obtained and maintained to make biomarkers effective instruments in support of therapeutic decisions. This overview focuses on preanalytical and analytical aspects to be considered for the implementation of new biomarkers for adjusting immunosuppression in a clinical setting and highlights critical points to be addressed on the way to make them suitable as diagnostic tools. These include but are not limited to appropriate method validation, standardization, education, automation, and commercialization.

  3. Estimation of biomarkers berberine and gallic acid in polyherbal formulation punarnavashtak kwath and its clinical study for hepatoprotective potential

    Directory of Open Access Journals (Sweden)

    Shah V

    2010-01-01

    Full Text Available Punarnavashtak (PN kwath is a classical Ayurvedic formulation mentioned in Ayurvedic literature "Bhaishyajyaratnavali" for hepatic disorders and asthma. Standardization and clinical trial to support its efficacy are lacking. So, in the present study, standardization of PN kwath was done by using biomarkers, gallic acid and berberine, and its hepatoprotective activity was evaluated by clinical study to rationalise the traditional use of this formulation. PN kwath was standardized by HPTLC (High performance thin layer chromatography using gallic acid and berberine as biomarkers and was subjected to clinical study. For clinical study patients attending outpatient clinics, with an evidence of liver disease were included in the study. During the study period, patients who fulfilled inclusion criteria were randomly assigned. The recommended dose was 20 ml kwath daily for 8 weeks. All the patients underwent clinical examination and laboratory investigations for liver functions tests before the commencement of therapy. Thereafter, clinical assessments were done after 8 weeks of treatment. The results showed significant changes in liver functions tests [serum glutamate oxaloacetate transaminase (SGOT, serum glutamate pyruvate transaminase (SGPT, alkaline phosphatase (ALP, total bilirubin]. There was no report of adverse effects attributable to this formulation. Our results suggest that PN kwath showed significant hepatoprotective activity. Berberine and gallic acid were found to be 0.08 and 4.9%, respectively. Our results suggest that PN kwath showed significant hepatoprotective activity due to presence of various phytoconstituents and support its traditional uses in liver disorder.

  4. Poor antibody validation is a challenge in biomedical research: a case study for detection of c-FLIP.

    Science.gov (United States)

    Bucur, Octavian; Pennarun, Bodvael; Stancu, Andreea Lucia; Nadler, Monica; Muraru, Maria Sinziana; Bertomeu, Thierry; Khosravi-Far, Roya

    2013-10-01

    Successful translation of findings derived from preclinical studies into effective therapies is critical in biomedical research. Lack of robustness and reproducibility of the preclinical data, due to insufficient number of repeats, inadequate cell-based and mouse models contribute to the poor success rate. Antibodies are widely used in preclinical research, notably to determine the expression of potential therapeutic targets in tissues of interest, including tumors, but also to identify disease and/or treatment response biomarkers. We sought to determine whether the current antibody characterization standards in preclinical research are sufficient to ensure reliability of the data found in peer-reviewed publications. To address this issue, we used detection of the protein c-FLIP, a major factor of resistance to apoptosis, as a proof of concept. Accurate detection of endogenous c-FLIP levels in the preclinical settings is imperative since it is considered as a potential theranostic biomarker. Several sources of c-FLIP antibodies validated by their manufacturer and recommended for western blotting were therefore rigorously tested. We found a wide divergence in immune recognition properties. While these antibodies have been used in many publications, our results show that several of them failed to detect endogenous c-FLIP protein by Western blotting. Our results suggest that antibody validation standards are inadequate, and that systematic use of genetic knockdowns and/or knockouts to establish proof of specificity is critical, even for antibodies previously used in the scientific literature. Because antibodies are fundamental tools in both preclinical and clinical research, ensuring their specificity is crucial.

  5. Magnitudes of biomarker reductions in response to controlled reductions in cigarettes smoked per day: a one-week clinical confinement study.

    Science.gov (United States)

    Theophilus, Eugenia H; Coggins, Christopher R E; Chen, Peter; Schmidt, Eckhardt; Borgerding, Michael F

    2015-03-01

    Tobacco toxicant-related exposure reduction is an important tool in harm reduction. Cigarette per day reduction (CPDR) occurs as smokers migrate from smoking cigarettes to using alternative tobacco/nicotine products, or quit smoking. Few reports characterize the dose-response relationships between CPDR and effects on exposure biomarkers, especially at the low end of CPD exposure (e.g., 5 CPD). We present data on CPDR by characterizing magnitudes of biomarker reductions. We present data from a well-controlled, one-week clinical confinement study in healthy smokers who were switched from smoking 19-25 CPD to smoking 20, 10, 5 or 0 CPD. Biomarkers were measured in blood, plasma, urine, and breath, and included smoke-related toxicants, urine mutagenicity, smoked cigarette filter analyses (mouth level exposure), and vital signs. Many of the biomarkers (e.g., plasma nicotine) showed strong CPDR dose-response reductions, while others (e.g., plasma thiocyanate) showed weaker dose-response reductions. Factors that lead to lower biomarker reductions include non-CPD related contributors to the measured response (e.g., other exposure sources from environment, life style, occupation; inter-individual variability). This study confirms CPDR dose-responsive biomarkers and suggests that a one-week design is appropriate for characterizing exposure reductions when smokers switch from cigarettes to new tobacco products.

  6. A Delphi Study and Initial Validation of Counselor Supervision Competencies

    Science.gov (United States)

    Neuer Colburn, Anita A.; Grothaus, Tim; Hays, Danica G.; Milliken, Tammi

    2016-01-01

    The authors addressed the lack of supervision training standards for doctoral counseling graduates by developing and validating an initial list of supervision competencies. They used content analysis, Delphi polling, and content validity methods to generate a list, vetted by 2 different panels of supervision experts, of 33 competencies grouped…

  7. Minimally invasive biomarker confirms glial activation present in Alzheimer's disease: a preliminary study

    Directory of Open Access Journals (Sweden)

    Tran T

    2011-08-01

    Full Text Available Napapon Sailasuta, Kent Harris, Thao Tran, Brian RossClinical MR Unit, Huntington Medical Research Institutes, Pasadena, CA, USAAbstract: We applied 13C magnetic resonance spectroscopy (MRS, a nonradioactive, noninvasive brain imaging technique, to quantify the oxidation of [1-13C] acetate in a conventional clinical magnetic resonance imaging (MRI scanner in five consecutive elderly subjects at various clinical stages of Alzheimer's disease (AD progression. [1-13C] acetate entered the brain and was metabolized to [5-13C] glutamate and glutamine, as well as [1-13C] glutamate and glutamine, and the final glial oxidation product, 13C bicarbonate, at a linear rate. Calculation of the initial slope was similar in a single subject, examined twice, 1 month apart (test-re-test 8%. Mean rate of cerebral bicarbonate production in this elderly group was 0.040 ± 0.01 (n = 5. Assuming that the rate of conversion of acetate to bicarbonate is a reflection of glial metabolic rate and that glial metabolic rate is a surrogate marker for 'neuroinflammation', our preliminary results suggest that [1-13C] MRS may provide biomarkers for diseases, believed to involve microglia and other cells of the astrocyte series. Among these is AD, for which novel drugs which ameliorate the damaging effects of neuroinflammation before symptoms of dementia appear, are in advanced development. The value of 13C MRS as an early, noninvasive biomarker may lie in the conduct of cost-effective clinical trials.Keywords: Alzheimer's disease, noninvasive biomarker, glial activation

  8. Validation of a multimarker model for assessing risk of type 2 diabetes from a five-year prospective study of 6784 Danish people (Inter99)

    DEFF Research Database (Denmark)

    Urdea, Mickey; Kolberg, Janice; Wilber, Judith;

    2009-01-01

    an individual's risk of developing diabetes. Here we describe the training and validation of the PreDx Diabetes Risk Score (DRS) model in a clinical laboratory setting using baseline serum samples from subjects in the Inter99 cohort, a population-based primary prevention study of cardiovascular disease.......Improved identification of subjects at high risk for development of type 2 diabetes would allow preventive interventions to be targeted toward individuals most likely to benefit. In previous research, predictive biomarkers were identified and used to develop multivariate models to assess...

  9. Biomarkers in Parkinson's disease: a funder's perspective.

    Science.gov (United States)

    Frasier, Mark; Chowdhury, Sohini; Eberling, Jamie; Sherer, Todd

    2010-10-01

    Therapeutic development in Parkinson's disease is hampered by the paucity of well-validated biomarkers that can assist with diagnosis and/or tracking the progression of the disease. Since its inception, the Michael J Fox Foundation for Parkinson's Research has invested heavily in biomarker research and continues to prioritize discovery and development efforts. This article summarizes the history and evolution of the Michael J Fox Foundation's role in supporting biomarker research and lays out the current challenges in successfully developing markers that can be used to test therapies, while also providing a vision of future funding efforts in Parkinson's disease biomarkers.

  10. Challenges and methodology in the incorporation of biomarkers in cancer clinical trials.

    Science.gov (United States)

    Wilhelm-Benartzi, Charlotte S; Mt-Isa, Shahrul; Fiorentino, Francesca; Brown, Robert; Ashby, Deborah

    2017-02-01

    Biomarkers can be used to establish more homogeneous groups using the genetic makeup of the tumour to inform the selection of treatment for each individual patient. However, proper preclinical work and stringent validation are needed before taking forward biomarkers into confirmatory studies. Despite the challenges, incorporation of biomarkers into clinical trials could better target appropriate patients, and potentially be lifesaving. The authors conducted a systematic review to describe marker-based and adaptive design methodology for their integration in clinical trials, and to further describe the associated practical challenges. Studies published between 1990 to November 2015 were searched on PubMed. Titles, abstracts and full text articles were reviewed to identify relevant studies. Of the 4438 studies examined, 57 studies were included. The authors conclude that the proposed approaches may readily help researchers to design biomarker trials, but novel approaches are still needed.

  11. Moral judgment reloaded: a moral dilemma validation study.

    Science.gov (United States)

    Christensen, Julia F; Flexas, Albert; Calabrese, Margareta; Gut, Nadine K; Gomila, Antoni

    2014-01-01

    We propose a revised set of moral dilemmas for studies on moral judgment. We selected a total of 46 moral dilemmas available in the literature and fine-tuned them in terms of four conceptual factors (Personal Force, Benefit Recipient, Evitability, and Intention) and methodological aspects of the dilemma formulation (word count, expression style, question formats) that have been shown to influence moral judgment. Second, we obtained normative codings of arousal and valence for each dilemma showing that emotional arousal in response to moral dilemmas depends crucially on the factors Personal Force, Benefit Recipient, and Intentionality. Third, we validated the dilemma set confirming that people's moral judgment is sensitive to all four conceptual factors, and to their interactions. Results are discussed in the context of this field of research, outlining also the relevance of our RT effects for the Dual Process account of moral judgment. Finally, we suggest tentative theoretical avenues for future testing, particularly stressing the importance of the factor Intentionality in moral judgment. Additionally, due to the importance of cross-cultural studies in the quest for universals in human moral cognition, we provide the new set dilemmas in six languages (English, French, German, Spanish, Catalan, and Danish). The norming values provided here refer to the Spanish dilemma set.

  12. Moral Judgment Reloaded: A Moral Dilemma validation study

    Directory of Open Access Journals (Sweden)

    Julia F. Christensen

    2014-07-01

    Full Text Available We propose a revised set of moral dilemmas for studies on moral judgment. We selected a total of 46 moral dilemmas available in the literature and fine-tuned them in terms of four conceptual factors (Personal Force, Benefit Recipient, Evitability and Intention and methodological aspects of the dilemma formulation (word count, expression style, question formats that have been shown to influence moral judgment. Second, we obtained normative codings of arousal and valence for each dilemma showing that emotional arousal in response to moral dilemmas depends crucially on the factors Personal Force, Benefit Recipient, and Intentionality. Third, we validated the dilemma set confirming that people's moral judgment is sensitive to all four conceptual factors, and to their interactions. Results are discussed in the context of this field of research, outlining also the relevance of our RT effects for the Dual Process account of moral judgment. Finally, we suggest tentative theoretical avenues for future testing, particularly stressing the importance of the factor Intentionality in moral judgment. Additionally, due to the importance of cross-cultural studies in the quest for universals in human moral cognition, we provide the new set dilemmas in six languages (English, French, German, Spanish, Catalan and Danish. The norming values provided here refer to the Spanish dilemma set.

  13. Algorithms for verbal autopsies: a validation study in Kenyan children.

    Science.gov (United States)

    Quigley, M. A.; Armstrong Schellenberg, J. R.; Snow, R. W.

    1996-01-01

    The verbal autopsy (VA) questionnaire is a widely used method for collecting information on cause-specific mortality where the medical certification of deaths in childhood is incomplete. This paper discusses review by physicians and expert algorithms as approaches to ascribing cause of deaths from the VA questionnaire and proposes an alternative, data-derived approach. In this validation study, the relatives of 295 children who had died in hospital were interviewed using a VA questionnaire. The children were assigned causes of death using data-derived algorithms obtained under logistic regression and using expert algorithms. For most causes of death, the data-derived algorithms and expert algorithms yielded similar levels of diagnostic accuracy. However, a data-derived algorithm for malaria gave a sensitivity of 71% (95% Cl: 58-84%), which was significantly higher than the sensitivity of 47% obtained under an expert algorithm. The need for exploring this and other ways in which the VA technique can be improved are discussed. The implications of less-than-perfect sensitivity and specificity are explored using numerical examples. Misclassification bias should be taken into consideration when planning and evaluating epidemiological studies. PMID:8706229

  14. Identifying Primary Spontaneous Pneumothorax from Administrative Databases: A Validation Study

    Directory of Open Access Journals (Sweden)

    Eric Frechette

    2016-01-01

    Full Text Available Introduction. Primary spontaneous pneumothorax (PSP is a disorder commonly encountered in healthy young individuals. There is no differentiation between PSP and secondary pneumothorax (SP in the current version of the International Classification of Diseases (ICD-10. This complicates the conduct of epidemiological studies on the subject. Objective. To validate the accuracy of an algorithm that identifies cases of PSP from administrative databases. Methods. The charts of 150 patients who consulted the emergency room (ER with a recorded main diagnosis of pneumothorax were reviewed to define the type of pneumothorax that occurred. The corresponding hospital administrative data collected during previous hospitalizations and ER visits were processed through the proposed algorithm. The results were compared over two different age groups. Results. There were 144 cases of pneumothorax correctly coded (96%. The results obtained from the PSP algorithm demonstrated a significantly higher sensitivity (97% versus 81%, p=0.038 and positive predictive value (87% versus 46%, p<0.001 in patients under 40 years of age than in older patients. Conclusions. The proposed algorithm is adequate to identify cases of PSP from administrative databases in the age group classically associated with the disease. This makes possible its utilization in large population-based studies.

  15. 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.

  16. 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.

  17. Summary of the HESI consortium studies exploring circulating inhibin B as a potential biomarker of testis damage in the rat.

    Science.gov (United States)

    Chapin, Robert; Weinbauer, Gerhard; Thibodeau, Michael S; Sonee, Manisha; Saldutti, Louise Parks; Reagan, William J; Potter, David; Moffit, Jeffrey S; Laffan, Susan; Kim, James H; Goldstein, Richard A; Erdos, Zoltan; Enright, Brian P; Coulson, Michelle; Breslin, William J

    2013-02-01

    The Developmental and Reproductive Toxicity Technical Committee of the Health and Environmental Sciences Institute hosted a working consortium of companies to evaluate a new commercially available analytic assay for Inhibin B in rat serum or plasma. After demonstrating that the kit was stable and robust, the group performed a series of independent pathogenesis studies (23 different compound/investigator combinations) designed to examine the correlation between the appearance of lesions in the testis and changes in circulating levels of Inhibin B. These studies were reported individually in the previous articles in this series (this issue), and are discussed in this paper. For roughly half of these exposures, lesions appeared well before Inhibin B changed. A few of the studies showed a good correlation between seminiferous tubule damage and reduced circulating Inhibin B levels, while for seven exposures, circulating Inhibin B was reduced with no detectable alteration in testis histology. Whether this indicates a prodromal response or a false-positive signal will require further investigation. These exceptions could plausibly suggest some value of circulating Inhibin B as a useful biomarker in some circumstances. However, for roughly half of these exposures, Inhibin B appeared to be a lagging biomarker, requiring significant damage to the seminiferous tubules before a consistent and credible reduction in circulating levels of Inhibin B was observed.

  18. Proteomics in Discovery of Hepatocellular Carcinoma Biomarkers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To discover new proteomic biomarkers of hepatocellular carcinoma. Methods: Surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry was used to discover biomarkers for differentiating hepatocellular carcinoma and chronic liver disease. A population of 50 patients with hepatocellular carcinoma and 33 patients with chronic liver disease was studied. Results: Twelve proteomic biomarkers of hepatocellular carcinoma were detected in this study. Three proteomic biomarkers were highly expressed in hepatocellular carcinoma and nine proteomic biomarkers were highly expressed in chronic liver disease. The most valuable proteomic biomarker with m/z=11498 had no similar diagnostic value as α-fetoprotein. Conclusion:Some of the twelve proteomic biomarkers may become new biomarkers of hepatocellular carcinoma.

  19. 41 CFR 60-3.14 - Technical standards for validity studies.

    Science.gov (United States)

    2010-07-01

    ... greater the need for other evidence of validity. (5) Reliability. The reliability of selection procedures... construct validity is both an extensive and arduous effort involving a series of research studies, which... validity studies. 60-3.14 Section 60-3.14 Public Contracts and Property Management Other...

  20. Cyber Victim and Bullying Scale: A Study of Validity and Reliability

    Science.gov (United States)

    Cetin, Bayram; Yaman, Erkan; Peker, Adem

    2011-01-01

    The purpose of this study is to develop a reliable and valid scale, which determines cyber victimization and bullying behaviors of high school students. Research group consisted of 404 students (250 male, 154 male) in Sakarya, in 2009-2010 academic years. In the study sample, mean age is 16.68. Content validity and face validity of the scale was…

  1. In Silico discovery of transcription factors as potential diagnostic biomarkers of ovarian cancer

    KAUST Repository

    Kaur, Mandeep

    2011-09-19

    Background: Our study focuses on identifying potential biomarkers for diagnosis and early detection of ovarian cancer (OC) through the study of transcription regulation of genes affected by estrogen hormone.Results: The results are based on a set of 323 experimentally validated OC-associated genes compiled from several databases, and their subset controlled by estrogen. For these two gene sets we computationally determined transcription factors (TFs) that putatively regulate transcription initiation. We ranked these TFs based on the number of genes they are likely to control. In this way, we selected 17 top-ranked TFs as potential key regulators and thus possible biomarkers for a set of 323 OC-associated genes. For 77 estrogen controlled genes from this set we identified three unique TFs as potential biomarkers.Conclusions: We introduced a new methodology to identify potential diagnostic biomarkers for OC. This report is the first bioinformatics study that explores multiple transcriptional regulators of OC-associated genes as potential diagnostic biomarkers in connection with estrogen responsiveness. We show that 64% of TF biomarkers identified in our study are validated based on real-time data from microarray expression studies. As an illustration, our method could identify CP2 that in combination with CA125 has been reported to be sensitive in diagnosing ovarian tumors. 2011 Kaur et al; licensee BioMed Central Ltd.

  2. In Silico discovery of transcription factors as potential diagnostic biomarkers of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Choolani Mahesh

    2011-09-01

    Full Text Available Abstract Background Our study focuses on identifying potential biomarkers for diagnosis and early detection of ovarian cancer (OC through the study of transcription regulation of genes affected by estrogen hormone. Results The results are based on a set of 323 experimentally validated OC-associated genes compiled from several databases, and their subset controlled by estrogen. For these two gene sets we computationally determined transcription factors (TFs that putatively regulate transcription initiation. We ranked these TFs based on the number of genes they are likely to control. In this way, we selected 17 top-ranked TFs as potential key regulators and thus possible biomarkers for a set of 323 OC-associated genes. For 77 estrogen controlled genes from this set we identified three unique TFs as potential biomarkers. Conclusions We introduced a new methodology to identify potential diagnostic biomarkers for OC. This report is the first bioinformatics study that explores multiple transcriptional regulators of OC-associated genes as potential diagnostic biomarkers in connection with estrogen responsiveness. We show that 64% of TF biomarkers identified in our study are validated based on real-time data from microarray expression studies. As an illustration, our method could identify CP2 that in combination with CA125 has been reported to be sensitive in diagnosing ovarian tumors.

  3. Development of metabolic function biomarkers in the common marmoset, Callithrix jacchus.

    Science.gov (United States)

    Ziegler, Toni E; Colman, Ricki J; Tardif, Suzette D; Sosa, Megan E; Wegner, Fredrick H; Wittwer, Daniel J; Shrestha, Hemanta

    2013-05-01

    Metabolic assessment of a non-human primate model of metabolic syndrome and obesity requires the necessary biomarkers specific to the species. While the rhesus monkey has a number of specific assays for assessing metabolic syndrome, the marmoset does not. Furthermore, the common marmoset (Callithrix jacchus) has a small blood volume that necessitates using a single blood volume for multiple analyses. The common marmoset holds a great potential as an alternative primate model for the study of human disease but assay methods need to be developed and validated for the biomarkers of metabolic syndrome. Here we report on the adaptation, development, and validation of commercially available immunoassays for common marmoset samples in small volumes. We have performed biological validations for insulin, adiponectin, leptin, and ghrelin to demonstrate the use of these biomarkers in examining metabolic syndrome and other related diseases in the common marmoset.

  4. Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Giovanni Nardo

    Full Text Available BACKGROUND: Amyotrophic lateral sclerosis (ALS is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments. METHODOLOGY/PRINCIPAL FINDINGS: We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC, a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%, and from patients with neurological disorders that may resemble ALS (91%, between two levels of disease severity (90%, and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing. CONCLUSIONS/SIGNIFICANCE: Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms.

  5. AFSC/REFM: Bomb-produced age validation study

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Fish age validation with bomb-produced radiocarbon (14C) requires a known-age Delta14C reference chronology spanning the era of a marine increase in bomb-produced...

  6. [Educational game of medication administration: a validation study].

    Science.gov (United States)

    Moreira, Amanda Portugal de Andrade; Sabóia, Vera Maria; Camacho, Alessandra Conceição Leite Funchal; Daher, Donizete Vago; Teixeira, Elizabeth

    2014-01-01

    This is a methodological research, which aimed to determine the validity of an educational technology (ET) in the form of educational game of medicine administration, according to the judges and audience, using the theoretical stage of Pasquali model. Data were collected between September 2011 and May 2012 in two stages: 1) application and validation of TE by forty students of the 4th period of Nursing, at the Fluminense Federal University (target audience); 2) observation and validation of TE by 8 teachers (judges). The questionnaires were organized in Likert scale, with items distributed in blocks and analyzed quantitatively. The game was validated, since it has over 80% approval by the two groups, and may therefore be used as a TE in the discipline of Fundamentals of Nursing. The results were positive, demonstrating that students and teachers are more interested in content taught when most dynamic technologies are used in the classroom.

  7. Chromodomain-helicase-DNA binding protein 5, 7 and pronecrotic mixed lineage kinase domain-like protein serve as potential prognostic biomarkers in patients with resected pancreatic adenocarcinomas

    Institute of Scientific and Technical Information of China (English)

    Crystal S Seldon; Lauren E Colbert; William A Hall; Sarah B Fisher; David S Yu; Jerome C Landry

    2016-01-01

    Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies.

  8. MINET validation study using steam generator test data

    Energy Technology Data Exchange (ETDEWEB)

    Van Tuyle, G.J.; Guppy, J.G.

    1984-01-01

    Three steam generator transient test cases that were simulated using the MINET computer code are described, with computed results compared against experimental data. The MINET calculations closely agreed with the experiment for both the once-through and the U-tube steam generator test cases. The effort is part of an ongoing effort to validate the MINET computer code for thermal-hydraulic plant systems transient analysis, and strongly supports the validity of the MINET models.

  9. Validation study of the Questionnaire on School Maladjustment Problems (QSMP).

    Science.gov (United States)

    de la Fuente Arias, Jesús; Peralta Sánchez, Francisco Javier; Sánchez Roda, María Dolores; Trianes Torres, María Victoria

    2012-05-01

    The aim of this study was to analyze the exploratory and confirmatory structure, as well as other psychometric properties, of the Cuestionario de Problemas de Convivencia Escolar (CPCE; in Spanish, the Questionnaire on School Maladjustment Problems [QSMP]), using a sample of Spanish adolescents. The instrument was administered to 60 secondary education teachers (53.4% females and 46.6% males) between the ages of 28 and 54 years (M= 41.2, SD= 11.5), who evaluated a total of 857 adolescent students. The first-order exploratory factor analysis identified 7 factors, explaining a total variance of 62%. A second-order factor analysis yielded three dimensions that explain 84% of the variance. A confirmatory factor analysis was subsequently performed in order to reduce the number of factors obtained in the exploratory analysis as well as the number of items. Lastly, we present the results of reliability, internal consistency, and validity indices. These results and their implications for future research and for the practice of educational guidance and intervention are discussed in the conclusions.

  10. Evaluation of RANKL/OPG Serum Concentration Ratio as a New Biomarker for Coronary Artery Calcification: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Amir Hooshang Mohammadpour

    2012-01-01

    Full Text Available Objective. There is a strong need for biomarkers to identify patients at risk for future cardiovascular events related with progressive atherosclerotic disease. Osteoprotegerin (OPG protects the skeleton from excessive bone resorption by binding to receptor activator of nuclear factor-κB ligand (RANKL and preventing it from binding to its receptor, receptor activator of nuclear factor-κB. However, conflicting results have been obtained about association of serum level of OPG or RANKL with coronary artery disease (CAD. Based on their role in inflammation and matrix degradation and the fact that atherosclerotic plaque formation is an inflammatory process, we hypothesized that RANKL : OPG ratio could be a better biomarker for CAD. Methods. In this cross-sectional study, the correlation between RANKL : OPG ratio serum concentration and coronary artery calcification (CAC in 50 patients with ischemic coronary disease has been investigated. We used ELISA method for measuring RANKL and OPG serum concentrations. Results. There was a significant correlation between RANKL : OPG serum concentration ratio and CAC in our study population (P=0.01. Conclusion. Our results suggested that RANKL : OPG ratio concentration has a potential of being used as a marker for coronary artery disease.

  11. A Validation Study of the Dutch Childhood Trauma Questionnaire-Short Form: Factor Structure, Reliability, and Known-Groups Validity

    Science.gov (United States)

    Thombs, Brett D.; Bernstein, David P.; Lobbestael, Jill; Arntz, Arnoud

    2009-01-01

    Objective: The 28-item Childhood Trauma Questionnaire-Short Form (CTQ-SF) has been translated into at least 10 different languages. The validity of translated versions of the CTQ-SF, however, has generally not been examined. The objective of this study was to investigate the factor structure, internal consistency reliability, and known-groups…

  12. Identification of Circulating Biomarker Candidates for Hepatocellular Carcinoma (HCC: An Integrated Prioritization Approach.

    Directory of Open Access Journals (Sweden)

    Faryal Mehwish Awan

    Full Text Available Hepatocellular carcinoma (HCC is the world's third most widespread cancer. Currently available circulating biomarkers for this silently progressing malignancy are not sufficiently specific and sensitive to meet all clinical needs. There is an imminent and pressing need for the identification of novel circulating biomarkers to increase disease-free survival rate. In order to facilitate the selection of the most promising circulating protein biomarkers, we attempted to define an objective method likely to have a significant impact on the analysis of vast data generated from cutting-edge technologies. Current study exploits data available in seven publicly accessible gene and protein databases, unveiling 731 liver-specific proteins through initial enrichment analysis. Verification of expression profiles followed by integration of proteomic datasets, enriched for the cancer secretome, filtered out 20 proteins including 6 previously characterized circulating HCC biomarkers. Finally, interactome analysis of these proteins with midkine (MDK, dickkopf-1 (DKK-1, current standard HCC biomarker alpha-fetoprotein (AFP, its interacting partners in conjunction with HCC-specific circulating and liver deregulated miRNAs target filtration highlighted seven novel statistically significant putative biomarkers including complement component 8, alpha (C8A, mannose binding lectin (MBL2, antithrombin III (SERPINC1, 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1, alcohol dehydrogenase 6 (ADH6, beta-ureidopropionase (UPB1 and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6. Our proposed methodology provides a swift assortment process for biomarker prioritization that eventually reduces the economic burden of experimental evaluation. Further dedicated validation studies of potential putative biomarkers on HCC patient blood samples are warranted. We hope that the use of such integrative secretome, interactome and miRNAs target filtration approach will

  13. 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.

  14. Measuring humeral head translation using fluoroscopy: a validation study.

    Science.gov (United States)

    San Juan, Jun G; Karduna, Andrew R

    2010-03-03

    Numerous techniques have been employed to monitor humeral head translation due to its involvement with several shoulder pathologies. However, most of the techniques were not validated. The objective of this study is to compare the accuracy of manual digitization and contour registration in measuring superior translation of the humeral head. Eight pairs of cadaver scapulae and humerii bones were harvested for this study. Each scapula and humerus was secured in a customized jig that allowed for control of humeral head translations and a vise that permitted rotations of the scapula about three axes. Fluoroscopy was used to take images of the shoulder bones. Scapular orientation was manipulated in different positions while the humerus was at 90 degrees of humeral elevation in the scapular plane. Humeral head translation was measured using the two methods and was compared to the known translation. Additionally, accuracy of the contour registration method to measure 2-D scapular rotations was assessed. The range for the root mean square (RMS) error for manual digitization method was 0.27 mm-0.43 mm and the contour registration method had a RMS error ranging from 0.18 mm-0.40 mm. In addition, the RMS error for the scapular angle rotation using the contour registration method was 2.4 degrees . Both methods showed acceptable errors. However, on average, the contour registration method showed lesser measurement error compared to the manual digitization method. In addition, the contour registration method was able to show good accuracy in measuring rotation that is useful in 2-D image analysis.

  15. Simultaneous quantification of biomarkers bergenin and menisdaurin in the methanol extract of aerial parts of Flueggea virosa by validated HPTLC densitometric method.

    Science.gov (United States)

    Siddiqui, Nasir A; Alam, Perwez; Al-Rehaily, Adnan J; Al-Oqail, Mai M; Parvez, Mohammad Khalid

    2015-01-01

    A simple, sensitive high-performance thin-layer chromatography (HPTLC) method was developed for the simultaneous quantification of biomarker bergenin and menisdaurin in the methanol extracts of aerial parts of Flueggea virosa (FVME). Chromatography was performed on glass-backed silica gel 60F254 HPTLC plates using dichloromethane: methanol as mobile phase. Scanning and quantification was done at UV absorption maxima of 260 nm. The system was found to give compact spot for bergenin and menisdaurin at Rf = 0.29 ± 0.01 and 0.16 ± 0.01, respectively. The linearity ranges for bergenin and menisdaurin were found to be the same (100-800 ng/spot) with correlation coefficients (R(2) values) of 0.997 and 0.999, respectively. The limit of detection for bergenin and menisdaurin was found to be 27 and 36.2 ng/band, respectively, while the limit of quantification was found to be 81 and 108 ng/band, respectively. Intra- and interday precisions (n = 6) for bergenin and menisdaurin were found to be 1.41-1.71 and 1.65-1.87%, and 1.68-1.89 and 1.75-1.93%, respectively. The percent recoveries were found to be 98.7-99.4 and 99.5-99.9%, respectively, for bergenin and menisdaurin. The percentage of bergenin and menisdaurin was found to be 15.25 and 4.22% (w/w), respectively, in FVME. The developed method permitted the simultaneous quantification of bergenin and menisdaurin and showed good resolution and separation from other constituents of extract; hence, the method can be used to standardize herbal formulations as well as bulk drugs for bergenin and menisdaurin.

  16. Plasma Brain-Derived Neurotrophic Factor as a Biomarker for the Main Types of Mild Neurocognitive Disorders and Treatment Efficacy: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Oleg A. Levada

    2016-01-01

    Full Text Available Decreased levels of brain-derived neurotrophic factor (BDNF are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs. In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer’s disease (MNCD-AD; 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD according to Frisoni et al. (2002 and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94% to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy.

  17. Plasma Brain-Derived Neurotrophic Factor as a Biomarker for the Main Types of Mild Neurocognitive Disorders and Treatment Efficacy: A Preliminary Study.

    Science.gov (United States)

    Levada, Oleg A; Cherednichenko, Nataliya V; Trailin, Andriy V; Troyan, Alexandra S

    2016-01-01

    Decreased levels of brain-derived neurotrophic factor (BDNF) are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs). In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram) in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer's disease (MNCD-AD); 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD) according to Frisoni et al. (2002) and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94%) to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy.

  18. Identification of consensus biomarkers for predicting non-genotoxic hepatocarcinogens

    Science.gov (United States)

    Huang, Shan-Han; Tung, Chun-Wei

    2017-01-01

    The assessment of non-genotoxic hepatocarcinogens (NGHCs) is currently relying on two-year rodent bioassays. Toxicogenomics biomarkers provide a potential alternative method for the prioritization of NGHCs that could be useful for risk assessment. However, previous studies using inconsistently classified chemicals as the training set and a single microarray dataset concluded no consensus biomarkers. In this study, 4 consensus biomarkers of A2m, Ca3, Cxcl1, and Cyp8b1 were identified from four large-scale microarray datasets of the one-day single maximum tolerated dose and a large set of chemicals without inconsistent classifications. Machine learning techniques were subsequently applied to develop prediction models for NGHCs. The final bagging decision tree models were constructed with an average AUC performance of 0.803 for an independent test. A set of 16 chemicals with controversial classifications were reclassified according to the consensus biomarkers. The developed prediction models and identified consensus biomarkers are expected to be potential alternative methods for prioritization of NGHCs for further experimental validation.

  19. Alaska North Slope Tundra Travel Model and Validation Study

    Energy Technology Data Exchange (ETDEWEB)

    Harry R. Bader; Jacynthe Guimond

    2006-03-01

    lack of variability in snow depth cover throughout the period of field experimentation. The amount of change in disturbance indicators was greater in the tundra communities of the Foothills than in those of the Coastal Plain. However the overall level of change in both community types was less than expected. In Coastal Plain communities, ground hardness and snow slab thickness were found to play an important role in change in active layer depth and soil moisture as a result of treatment. In the Foothills communities, snow cover had the most influence on active layer depth and soil moisture as a result of treatment. Once certain minimum thresholds for ground hardness, snow slab thickness, and snow depth were attained, it appeared that little or no additive effect was realized regarding increased resistance to disturbance in the tundra communities studied. DNR used the results of this modeling project to set a standard for maximum permissible disturbance of cross-country tundra travel, with the threshold set below the widely accepted standard of Low Disturbance levels (as determined by the U.S. Fish and Wildlife Service). DNR followed the modeling project with a validation study, which seemed to support the field trial conclusions and indicated that the standard set for maximum permissible disturbance exhibits a conservative bias in favor of environmental protection. Finally DNR established a quick and efficient tool for visual estimations of disturbance to determine when investment in field measurements is warranted. This Visual Assessment System (VAS) seemed to support the plot disturbance measurements taking during the modeling and validation phases of this project.

  20. Urinary biomarkers of smokers' exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach.

    Science.gov (United States)

    Gregg, Evan O; Minet, Emmanuel; McEwan, Michael

    2013-09-01

    There are established guidelines for bioanalytical assay validation and qualification of biomarkers. In this review, they were applied to a panel of urinary biomarkers of tobacco smoke exposure as part of a "fit for purpose" approach to the assessment of smoke constituents exposure in groups of tobacco product smokers. Clinical studies have allowed the identification of a group of tobacco exposure biomarkers demonstrating a good doseresponse relationship whilst others such as dihydroxybutyl mercapturic acid and 2-carboxy-1-methylethylmercapturic acid - did not reproducibly discriminate smokers and non-smokers. Furthermore, there are currently no agreed common reference standards to measure absolute concentrations and few inter-laboratory trials have been performed to establish consensus values for interim standards. Thus, we also discuss in this review additional requirements for the generation of robust data on urinary biomarkers, including toxicant metabolism and disposition, method validation and qualification for use in tobacco products comparison studies.

  1. Physics validation studies for muon collider detector background simulations

    Energy Technology Data Exchange (ETDEWEB)

    Morris, Aaron Owen; /Northern Illinois U.

    2011-07-01

    Within the broad discipline of physics, the study of the fundamental forces of nature and the most basic constituents of the universe belongs to the field of particle physics. While frequently referred to as 'high-energy physics,' or by the acronym 'HEP,' particle physics is not driven just by the quest for ever-greater energies in particle accelerators. Rather, particle physics is seen as having three distinct areas of focus: the cosmic, intensity, and energy frontiers. These three frontiers all provide different, but complementary, views of the basic building blocks of the universe. Currently, the energy frontier is the realm of hadron colliders like the Tevatron at Fermi National Accelerator Laboratory (Fermilab) or the Large Hadron Collider (LHC) at CERN. While the LHC is expected to be adequate for explorations up to 14 TeV for the next decade, the long development lead time for modern colliders necessitates research and development efforts in the present for the next generation of colliders. This paper focuses on one such next-generation machine: a muon collider. Specifically, this paper focuses on Monte Carlo simulations of beam-induced backgrounds vis-a-vis detector region contamination. Initial validation studies of a few muon collider physics background processes using G4beamline have been undertaken and results presented. While these investigations have revealed a number of hurdles to getting G4beamline up to the level of more established simulation suites, such as MARS, the close communication between us, as users, and the G4beamline developer, Tom Roberts, has allowed for rapid implementation of user-desired features. The main example of user-desired feature implementation, as it applies to this project, is Bethe-Heitler muon production. Regarding the neutron interaction issues, we continue to study the specifics of how GEANT4 implements nuclear interactions. The GEANT4 collaboration has been contacted regarding the minor

  2. Propeller aircraft interior noise model utilization study and validation

    Science.gov (United States)

    Pope, L. D.

    1984-01-01

    Utilization and validation of a computer program designed for aircraft interior noise prediction is considered. The program, entitled PAIN (an acronym for Propeller Aircraft Interior Noise), permits (in theory) predictions of sound levels inside propeller driven aircraft arising from sidewall transmission. The objective of the work reported was to determine the practicality of making predictions for various airplanes and the extent of the program's capabilities. The ultimate purpose was to discern the quality of predictions for tonal levels inside an aircraft occurring at the propeller blade passage frequency and its harmonics. The effort involved three tasks: (1) program validation through comparisons of predictions with scale-model test results; (2) development of utilization schemes for large (full scale) fuselages; and (3) validation through comparisons of predictions with measurements taken in flight tests on a turboprop aircraft. Findings should enable future users of the program to efficiently undertake and correctly interpret predictions.

  3. Biomarkers for early detection of Alzheimer disease.

    Science.gov (United States)

    Barber, Robert C

    2010-09-01

    The existence of an effective biomarker for early detection of Alzheimer disease would facilitate improved diagnosis and stimulate therapeutic trials. Multidisciplinary clinical diagnosis of Alzheimer disease is time consuming and expensive and relies on experts who are rarely available outside of specialty clinics. Thus, many patients do not receive proper diagnosis until the disease has progressed beyond stages in which treatments are maximally effective. In the clinical trial setting, rapid, cost-effective screening of patients for Alzheimer disease is of paramount importance for the development of new treatments. Neuroimaging of cortical amyloid burden and volumetric changes in the brain and assessment of protein concentrations (eg, β-amyloid 1-42, total tau, phosphorylated tau) in cerebrospinal fluid are diagnostic tools that are not widely available. Known genetic markers do not provide sufficient discriminatory power between different forms of dementia to be useful in isolation. Recent studies using panels of biomarkers for diagnosis of Alzheimer disease or mild cognitive impairment have been promising, though no such studies have been cross-validated in independent samples of subjects. The ideal biomarker enabling early detection of Alzheimer disease has not yet been identified.

  4. 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

  5. Assessing vitamin status in large population surveys by measuring biomarkers and dietary intake – two case studies: folate and vitamin D

    Directory of Open Access Journals (Sweden)

    Christine M. Pfeiffer

    2012-04-01

    Full Text Available The National Health and Nutrition Examination Survey (NHANES provides the most comprehensive assessment of the health and nutrition status of the US population. Up-to-date reference intervals on biomarkers and dietary intake inform the scientific and public health policy communities on current status and trends over time.The main purpose of dietary assessment methods such as the food-frequency questionnaire, food record (or diary, and 24-hr dietary recall is to estimate intake of nutrients and, together with supplement usage information, describe total intake of various foods or nutrients. As with all self-reporting methods, these tools are challenging to use and interpret. Yet, they are needed to establish dietary reference intake recommendations and to evaluate what proportion of the population meets these recommendations. While biomarkers are generally expensive and, to some degree, invasive, there is no question as to their ability to assess nutrition status. In some cases biomarkers can also be used to assess intake or function, although rarely can one biomarker fulfill all these purposes. For example, serum folate is a good indicator of folate intake, red blood cell (RBC folate is a good status indicator, and plasma total homocysteine is a good functional indicator of one-carbon metabolism.Using folate and vitamin D – two vitamins that are currently hotly debated in the public health arena – as two case studies, we discuss the complexities of using biomarkers and total intake information to assess nutrition status. These two examples also show how biomarkers and intake provide different information and how both are needed to evaluate and set public health policy. We also provide guidance on general requirements for using nutrition biomarkers and food and supplement intake information in longitudinal, population-based surveys.

  6. 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.

  7. Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer.

    Science.gov (United States)

    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

    2012-10-01

    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 (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.

  8. Identification of Pharmacodynamic Transcript Biomarkers in Response to FGFR Inhibition by AZD4547.

    Science.gov (United States)

    Delpuech, Oona; Rooney, Claire; Mooney, Lorraine; Baker, Dawn; Shaw, Robert; Dymond, Michael; Wang, Dennis; Zhang, Pei; Cross, Sarah; Veldman-Jones, Margaret; Wilson, Joanne; Davies, Barry R; Dry, Jonathan R; Kilgour, Elaine; Smith, Paul D

    2016-11-01

    The challenge of developing effective pharmacodynamic biomarkers for preclinical and clinical testing of FGFR signaling inhibition is significant. Assays that rely on the measurement of phospho-protein epitopes can be limited by the availability of effective antibody detection reagents. Transcript profiling enables accurate quantification of many biomarkers and provides a broader representation of pathway modulation. To identify dynamic transcript biomarkers of FGFR signaling inhibition by AZD4547, a potent inhibitor of FGF receptors 1, 2, and 3, a gene expression profiling study was performed in FGFR2-amplified, drug-sensitive tumor cell lines. Consistent with known signaling pathways activated by FGFR, we identified transcript biomarkers downstream of the RAS-MAPK and PI3K/AKT pathways. Using different tumor cell lines in vitro and xenografts in vivo, we confirmed that some of these transcript biomarkers (DUSP6, ETV5, YPEL2) were modulated downstream of oncogenic FGFR1, 2, 3, whereas others showed selective modulation only by FGFR2 signaling (EGR1). These transcripts showed consistent time-dependent modulation, corresponding to the plasma exposure of AZD4547 and inhibition of phosphorylation of the downstream signaling molecules FRS2 or ERK. Combination of FGFR and AKT inhibition in an FGFR2-mutated endometrial cancer xenograft model enhanced modulation of transcript biomarkers from the PI3K/AKT pathway and tumor growth inhibition. These biomarkers were detected on the clinically validated nanoString platform. Taken together, these data identified novel dynamic transcript biomarkers of FGFR inhibition that were validated in a number of in vivo models, and which are more robustly modulated by FGFR inhibition than some conventional downstream signaling protein biomarkers. Mol Cancer Ther; 15(11); 2802-13. ©2016 AACR.

  9. Capsaicinoids, chloropicrin and sulfur mustard: Possibilities for exposure biomarkers

    Directory of Open Access Journals (Sweden)

    Maija Pesonen

    2010-12-01

    Full Text Available Incapacitating and irritating agents produce temporary disability persisting for hours to days after the exposure. One can be exposed to these agents occupationally in industrial or other working environments. Also general public can be exposed in special circumstances, like industrial accidents or riots. Incapacitating and irritating agents discussed in this review are chloropicrin and capsaicinoids. In addition, we include sulfur mustard, which is an old chemical warfare agent and known to cause severe long-lasting injuries or even death. Chloropicrin that was used as a warfare agent in the World War I is currently used mainly as a pesticide. Capsaicinoids, components of hot pepper plants, are used by police and other law enforcement personnel as riot control agents. Toxicity of these chemicals is associated particularly with the respiratory tract, eyes and skin. Their acute effects are relatively well known but the knowledge of putative long-term effects is almost non-existent. Also, mechanisms of effects at cellular level are not fully understood. There is a need for further research to get better idea of health risks, particularly of long-term and low-level exposures to these chemicals. For this, exposure biomarkers are essential. Validated exposure biomarkers for capsaicinoids, chloropicrin and sulfur mustard do not exist so far. Metabolites and macromolecular adducts have been suggested biomarkers for sulfur mustard and these can already be measured qualitatively, but quantitative biomarkers await further development and validation. The purpose of this review is, based on the existing mechanistic and toxicokinetic information, to shed light on the possibilities for developing biomarkers for exposure biomonitoring of these compounds. It is also of interest to find ideas for early effect biomarkers considering the need for studies on subchronic and chronic toxicity.

  10. Neuroimaging Biomarkers for Psychosis

    Science.gov (United States)

    Hager, Brandon M.

    2015-01-01

    Background Biomarkers provide clinicians with a predictable model for the diagnosis, treatment and follow-up of medical ailments. Psychiatry has lagged behind other areas of medicine in the identification of biomarkers for clinical diagnosis and treatment. In this review, we investigated the current state of neuroimaging as it pertains to biomarkers for psychosis. Methods We reviewed systematic reviews and meta-analyses of the structural (sMRI), functional (fMRI), diffusion-tensor (DTI), Positron emission tomography (PET) and spectroscopy (MRS) studies of subjects at-risk or those with an established schizophrenic illness. Only articles reporting effect-sizes and confidence intervals were included in an assessment of robustness. Results Out of the identified meta-analyses and systematic reviews, 21 studies met the inclusion criteria for assessment. There were 13 sMRI, 4 PET, 3 MRS, and 1 DTI studies. The search terms included in the current review encompassed familial high risk (FHR), clinical high risk (CHR), First episode (FES), Chronic (CSZ), schizophrenia spectrum disorders (SSD), and healthy controls (HC). Conclusions Currently, few neuroimaging biomarkers can be considered ready for diagnostic use in patients with psychosis. At least in part, this may be related to the challenges inherent in the current symptom-based approach to classifying these disorders. While available studies suggest a possible value of imaging biomarkers for monitoring disease progression, more systematic research is needed. To date, the best value of imaging data in psychoses has been to shed light on questions of disease pathophysiology, especially through the characterization of endophenotypes. PMID:25883891

  11. The global status of freshwater fish age validation studies and a prioritization framework for future research

    Science.gov (United States)

    Pope, Kevin L.; Hamel, Martin J.; Pegg, Mark A.; Spurgeon, Jonathan J.

    2016-01-01

    Age information derived from calcified structures is commonly used to estimate recruitment, growth, and mortality for fish populations. Validation of daily or annual marks on age structures is often assumed, presumably due to a lack of general knowledge concerning the status of age validation studies. Therefore, the current status of freshwater fish age validation studies was summarized to show where additional effort is needed, and increase the accessibility of validation studies to researchers. In total, 1351 original peer-reviewed articles were reviewed from freshwater systems that studied age in fish. Periodicity and age validation studies were found for 88 freshwater species comprising 21 fish families. The number of age validation studies has increased over the last 30 years following previous calls for more research; however, few species have validated structures spanning all life stages. In addition, few fishes of conservation concern have validated ageing structures. A prioritization framework, using a combination of eight characteristics, is offered to direct future age validation studies and close the validation information gap. Additional study, using the offered prioritization framework, and increased availability of published studies that incorporate uncertainty when presenting research results dealing with age information are needed.

  12. Urine flavonoids and plasma carotenoids in the validation of fruit, vegetable and tea intake during pregnancy in the Norwegian Mother and Child Cohort Study (MoBa)

    DEFF Research Database (Denmark)

    Brantsaeter, Anne Lise; Haugen, Margaretha; Rasmussen, Salka E.

    2007-01-01

    estimate of fruit intake was significantly correlated with urine phloretin (r = 0.33), citrus fruit/juice with urine hesperetin (r = 0.44), cooked vegetables with plasma alpha-carotene (r = 0.37), and tea with urine kaempferol (r = 0.41) (P ... into the same or adjacent quintiles when classified by FFQ and biomarkers. Significant correlations between the FFQ and FD were found for fruit (r = 0.39), vegetables (r = 0.34), juices of triads (r = 0.50) and tea (r = 0.53). The FFQ validity coefficient was 0.65 for citrus fruit/juice and 0.59 for cooked...... vegetables as calculated by the triangular method. Conclusions: The validation study shows that the MoBa FFQ can be used to estimate fruit, juice, vegetable and tea intake in pregnant Norwegian women, and to rank individuals within the distribution....

  13. A Validity Study of the Salter Environmental Type Assessment.

    Science.gov (United States)

    Salter, Daniel W.

    2002-01-01

    Correlational analyses of data from 202 students on the Work Environment Scale and Salter Environmental Type Assessment (SETA) supported concurrent validity. Factor analysis identified three factors accounting for 70% of variance: positive work settings, structure, and work pressure/task orientation. SETA appears useful as a commensurate Myers…

  14. Measuring Elementary Student's Mathematics Motivation: A Validity Study

    Science.gov (United States)

    Orosco, Michael J.

    2016-01-01

    The psychometric properties of a 10-item math motivation scale were empirically validated with an independent sample consisting of 182 elementary-school students. Analysis of the model dimensionality supported a one-factor structure fit. Item parameter estimates from a Classical Test Theory framework revealed that most items were highly…

  15. Biomarkers in the pathogenesis, diagnosis, and treatment of psoriasis

    Directory of Open Access Journals (Sweden)

    Molteni S

    2012-09-01

    Full Text Available Silvia Molteni, Eva RealiLaboratory of Translational Immunology, Istituto Ortopedico Galeazzi, Milan, ItalyAbstract: Development of psoriasis results from a complex interplay between genetically predisposing factors and environmental triggers that give rise to a self-sustaining pathogenic cycle involving T cells, dendritic cells, connective tissue, and skin epithelium. From 5% to 40% of patients with psoriasis also develop psoriatic arthritis, and increasing evidence indicates an association with other systemic manifestations, including cardiovascular disease and the metabolic syndrome. In psoriatic disease, there is a need for development of biomarkers for assessment of disease severity, for prediction of the outcome of therapeutic interventions, and for distinction between the different clinical variants of the disease. A field of great importance is identification of biomarkers for prediction of development of comorbidities, such as arthritis, cardiovascular disease, and the metabolic syndrome. Genetic determinants of psoriasis and their products not only give an important insight into the pathogenesis of the disease, but may also function as markers of risk for developing cutaneous psoriasis or psoriatic arthritis. So far, there are limited validation data to support the use of candidate biomarkers in clinical practice. Here we review the data from several studies on some of the most promising candidate biomarkers for cutaneous psoriasis and psoriatic arthritis, for the detection of systemic inflammation, and for use as endpoints for therapeutic interventions. Attention is focused on the molecules that take part in the interplay giving rise to psoriasis and on gene products that may represent a link between predisposing genetic factors and the immune and inflammatory processes involved in pathogenesis of the disease. Finally, we provide an overview on how biomarkers can offer insights into the pathogenesis and natural history of psoriasis

  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.

  17. Biomarkers for predicting complete debulking in ovarian cancer

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten Lindberg; Ottesen, Bent; Christensen, Ib Jarle;

    2014-01-01

    Aim: We aimed to construct and validate a model based on biomarkers to predict complete primary debulking surgery for ovarian cancer patients.......Aim: We aimed to construct and validate a model based on biomarkers to predict complete primary debulking surgery for ovarian cancer patients....

  18. Alternatively Spliced Genes as Biomarkers for Schizophrenia, Bipolar Disorder and Psychosis: A Blood-Based Spliceome-Profiling Exploratory Study.

    Science.gov (United States)

    Glatt, S J; Chandler, S D; Bousman, C A; Chana, G; Lucero, G R; Tatro, E; May, T; Lohr, J B; Kremen, W S; Everall, I P; Tsuang, M T

    2009-09-01

    OBJECTIVE: Transcriptomic biomarkers of psychiatric diseases obtained from a query of peripheral tissues that are clinically accessible (e.g., blood cells instead of post-mortem brain tissue) have substantial practical appeal to discern the molecular subtypes of common complex diseases such as major psychosis. To this end, spliceome-profiling is a new methodological approach that has considerable conceptual relevance for discovery and clinical translation of novel biomarkers for psychiatric illnesses. Advances in microarray technology now allow for improved sensitivity in measuring the transcriptome while simultaneously querying the "exome" (all exons) and "spliceome" (all alternatively spliced variants). The present study aimed to evaluate the feasibility of spliceome-profiling to discern transcriptomic biomarkers of psychosis. METHODS: We measured exome and spliceome expression in peripheral blood mononuclear cells from 13 schizophrenia patients, nine bipolar disorder patients, and eight healthy control subjects. Each diagnostic group was compared to each other, and the combined group of bipolar disorder and schizophrenia patients was also compared to the control group. Furthermore, we compared subjects with a history of psychosis to subjects without such history. RESULTS: After applying Bonferroni corrections for the 21,866 full-length gene transcripts analyzed, we found significant interactions between diagnostic group and exon identity, consistent with group differences in rates or types of alternative splicing. Relative to the control group, 18 genes in the bipolar disorder group, eight genes in the schizophrenia group, and 15 genes in the combined bipolar disorder and schizophrenia group appeared differentially spliced. Importantly, thirty-three genes showed differential splicing patterns between the bipolar disorder and schizophrenia groups. More frequent exon inclusion and/or over-expression was observed in psychosis. Finally, these observations are

  19. The consequences of lead acetate intake on exposure and integrity biomarkers of reproductive system in female rats at sexual maturity (two generation study

    Directory of Open Access Journals (Sweden)

    Eugenia Dumitrescu

    2010-06-01

    Full Text Available The aim of the study was the assessment of lead toxic impact on female reproductive systemintegrity and performances biomarkers. The objectives were: the evaluation of lead levels in ovary,Fallopian tubes and uterus (exposure biomarker and the structural changes in ovary, Fallopian tubesand uterus (integrity biomarker at sexual maturity consecutive exposure to lead acetate (50, 100, 150ppb Pb in drinking water along two generation (F0, F1. The study pointed out significant increase of leadlevel in ovaries, Fallopian tubes and uterus comparative to the control group and direct corelation, withdifferent degrees of significance, with the exposure level; severe congestive and degenerative changes inovary (destruction of parenchymatosa zone, vacuolar epithelial cells, passive vascular congestion,edematous follicle without oocytes, follicle with oocytes and uterus (necrosis of uterine glands,destruction of uterine lining cells, total detachments of the superficial layers of the epithelia, hypertrophyof the epithelia.

  20. 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.

  1. 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 BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSION: 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.

  2. DEVELOPING OF INDIVIDUAL INSTRUMENT PERFORMANCE ANXIETY SCALE: VALIDITY - RELIABILITY STUDY

    Directory of Open Access Journals (Sweden)

    Esra DALKIRAN

    2014-07-01

    Full Text Available The purpose of this study is to develop a scale unique to our culture, concerning  individual instrument performance anxiety of the students  who are getting instrument training  in the Department of Music Education. In the study, the descriptive research model is used and qualitative research techniques are utilized. The study population consists of the students attending the 23 universities which has Music Education Department. The sample of the study consists of 438 girls and 312 boys, totally 750 students  who are studying in the Department of Music Education of randomly selected 10 universities. As a result of the explanatory and confirmatory factor analyses that were performed, a one-dimensional structure consisting of 14 items was obtained. Also, t-scores and  the coefficient scores of total item correlation concerning the distinguishing power of the items, the difference in the scores of the set of lower and upper 27% was calculated, and it was observed that the items are distinguishing as a result of both analyses. Of the scale, Cronbach's alpha coefficient of internal consistency was calculated as .94, and test-retest reliability coefficient was calculated as .93. As a result, a valid and reliable assessment and evaluation instrument that measures the exam performance anxiety of the students studying in the Department of Music Education, has been developed.Extended AbstractsIntroductionAnxiety is a universal phenomenon which people experience once or a few times during lives. It was accepted as concern for the future or as an unpleasant emotional experience regarding probable hitches of the events (Di Tomasso & Gosch, 2002.In general, the occasions on which negative feelings are experienced cause anxiety to arise (Baltaş and Baltaş, 2000. People also feel anxious in dangerous situations. Anxiety may lead a person to be creative, while it may have hindering characteristics. Anxiety is that an individual considers him

  3. [Biomarkers in rheumatology. Biomarkers and imaging for the diagnosis and stratification of rheumatoid arthritis and spondylarthritis in the ArthroMark network funded by the Federal Ministry of Education and Research].

    Science.gov (United States)

    Häupl, T; Appel, H; Backhaus, M; Burkhardt, H; Grünke, M; Grützkau, A; Hoppe, B; Listing, J; Ostendorf, B; Rudwaleit, M; Sieper, J; Skapenko, A; Skriner, K; Sörensen, T; Stuhlmüller, B; Zink, A; Schulze-Koops, H; Burmester, G-R

    2012-06-01

    The introduction of biologics has continuously increased the demand for biomarkers for early diagnosis and therapeutic stratification. ArthroMark, a research network funded by the Federal Ministry of Education and Research, aims to establish such biomarkers for rheumatoid arthritis and spondyloarthritides. Biobanks and previous work on genotyping, gene expression and autoreactivity profiling build the basis. Bioinformatic networks will help to harmonize the investigations and a clinical study with modern imaging techniques to characterize the functional relevance of the new biomarkers as effectively as possible. To validate the markers for diagnostic application the network aims to expand gradually.

  4. A biomarker study of high resolution sedimentary records in the eastern Mediterranean Sea since the last glacial maximum

    Science.gov (United States)

    Katsouras, G.; Gogou, A.; Bouloubassi, I.; Emeis, K.-C.; Triantaphyllou, M. V.; Lykousis, V.

    2009-04-01

    Information stored in sedimentary records provides evidence on climate and environmental variability at decadal to centennial time scales. The eastern Mediterranean Sea and the related Aegean Sea exhibit high sedimentation rates in certain areas and are considered as sensitive regions to record paleo-environmental and -climatic changes. The aim of our study is to reconstruct high-frequency paleoclimatic variations and identify associated changes in the physical, chemical and biological environment in selected basins of the eastern Mediterranean Sea, using molecular biogeochemical proxies. Here we present a high-resolution multi-proxy study along two Aegean Sea cores (north (152SL) and southeast (NS-14)) and a Libyan Sea core (HCM2/22). An important time marker and indicator of remarkable climatic and environmental changes is sapropel S1, a sediment layer rich in organic carbon. Depending on the water column depth, the sediment accumulation rates and the proximity to freshwater and water formation sources, S1 deposited between ~9.8 to 6.4 kyr BP, with an apparent interruption in the S1 deposition that occurred from ~8.6 to 7.6 kyr BP. SSTs based on alkenone unsaturation index Uḱ 37, ^15tot, ^13Corg and various marine and terrestrial biomarkers are used to investigate the region's climatic variability, and the modifications in the biogeochemical functioning of the eastern Mediterranean Sea. Uḱ 37 SST distribution in our records reveals significant fluctuations in temperature over the last 20.000 yrs. Organic carbon stable isotopes values span a narrow range over the whole sequence, with values varying to typical marine origin. The distributions of land-plant biomarkers are indicative of variable terrigenous organic matter supply and the concomitant transport of nutrients to surface waters. Furthermore, the distribution patterns and characteristic ratios of marine biomarkers exhibit differences in the paleoproductivity trends and ventilation changes over the last

  5. Infrared spectroscopic studies of cells and tissues: triple helix proteins as a potential biomarker for tumors.

    Science.gov (United States)

    Stelling, Allison L; Toher, Deirdre; Uckermann, Ortrud; Tavkin, Jelena; Leipnitz, Elke; Schweizer, Julia; Cramm, Holger; Steiner, Gerald; Geiger, Kathrin D; Kirsch, Matthias

    2013-01-01

    In this work, the infrared (IR) spectra of living neural cells in suspension, native brain tissue, and native brain tumor tissue were investigated. Methods were developed to overcome the strong IR signal of liquid water so that the signal from the cellular biochemicals could be seen. Measurements could be performed during surgeries, within minutes after resection. Comparison between normal tissue, different cell lineages in suspension, and tumors allowed preliminary assignments of IR bands to be made. The most dramatic difference between tissues and cells was found to be in weaker IR absorbances usually assigned to the triple helix of collagens. Triple helix domains are common in larger structural proteins, and are typically found in the extracellular matrix (ECM) of tissues. An algorithm to correct offsets and calculate the band heights and positions of these bands was developed, so the variance between identical measurements could be assessed. The initial results indicate the triple helix signal is surprisingly consistent between different individuals, and is altered in tumor tissues. Taken together, these preliminary investigations indicate this triple helix signal may be a reliable biomarker for a tumor-like microenvironment. Thus, this signal has potential to aid in the intra-operational delineation of brain tumor borders.

  6. Infrared spectroscopic studies of cells and tissues: triple helix proteins as a potential biomarker for tumors.

    Directory of Open Access Journals (Sweden)

    Allison L Stelling

    Full Text Available In this work, the infrared (IR spectra of living neural cells in suspension, native brain tissue, and native brain tumor tissue were investigated. Methods were developed to overcome the strong IR signal of liquid water so that the signal from the cellular biochemicals could be seen. Measurements could be performed during surgeries, within minutes after resection. Comparison between normal tissue, different cell lineages in suspension, and tumors allowed preliminary assignments of IR bands to be made. The most dramatic difference between tissues and cells was found to be in weaker IR absorbances usually assigned to the triple helix of collagens. Triple helix domains are common in larger structural proteins, and are typically found in the extracellular matrix (ECM of tissues. An algorithm to correct offsets and calculate the band heights and positions of these bands was developed, so the variance between identical measurements could be assessed. The initial results indicate the triple helix signal is surprisingly consistent between different individuals, and is altered in tumor tissues. Taken together, these preliminary investigations indicate this triple helix signal may be a reliable biomarker for a tumor-like microenvironment. Thus, this signal has potential to aid in the intra-operational delineation of brain tumor borders.

  7. Environmental education curriculum evaluation questionnaire: A reliability and validity study

    Science.gov (United States)

    Minner, Daphne Diane

    The intention of this research project was to bridge the gap between social science research and application to the environmental domain through the development of a theoretically derived instrument designed to give educators a template by which to evaluate environmental education curricula. The theoretical base for instrument development was provided by several developmental theories such as Piaget's theory of cognitive development, Developmental Systems Theory, Life-span Perspective, as well as curriculum research within the area of environmental education. This theoretical base fueled the generation of a list of components which were then translated into a questionnaire with specific questions relevant to the environmental education domain. The specific research question for this project is: Can a valid assessment instrument based largely on human development and education theory be developed that reliably discriminates high, moderate, and low quality in environmental education curricula? The types of analyses conducted to answer this question were interrater reliability (percent agreement, Cohen's Kappa coefficient, Pearson's Product-Moment correlation coefficient), test-retest reliability (percent agreement, correlation), and criterion-related validity (correlation). Face validity and content validity were also assessed through thorough reviews. Overall results indicate that 29% of the questions on the questionnaire demonstrated a high level of interrater reliability and 43% of the questions demonstrated a moderate level of interrater reliability. Seventy-one percent of the questions demonstrated a high test-retest reliability and 5% a moderate level. Fifty-five percent of the questions on the questionnaire were reliable (high or moderate) both across time and raters. Only eight questions (8%) did not show either interrater or test-retest reliability. The global overall rating of high, medium, or low quality was reliable across both coders and time, indicating

  8. [Pilot study on predictive value of plasmatic levels of 9 angiogenetic biomarkers in selection of patients candidate to prostate biopsy].

    Science.gov (United States)

    Serretta, Vincenzo; Scurria, Salvatore; Dispensa, Nino; Chiapparrone, Gaetano; Provenzano, Sandro; Caruso, Stefano; Bronte, Giuseppe; Cicero, Giuseppe; Russo, Antonio

    2013-01-01

    To reduce the number of negative prostate biopsies in patients with elevated PSA serum levels represents a major challenge in urological oncology. Angiogenetic factors might be involved in initial stages of prostate cancer and might represent useful tools in patients' selection for prostate biopsy. The plasmatic levels of Angiopoietin-2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF were measured by BioPlex immunoassay in patients undergoing prostate biopsy for palpable prostate nodule and/or elevated PSA levels (≥4 ng/mL). They were related with biopsy results. ROC curve analysis was exploited to test the diagnostic accuracy of each biomarker by AUC calculation. A potential cut-off level was computed. Fifty patients were entered. Median PSA was 6.8 ng/mL. A prostate nodule was palpable in 18 (36%) patients. The median number of biopsy cores was 12. Prostate cancer was detected in 25 (50%) and ASAP and PIN in 2 more patients (4%) respectively. Among the 9 considered biomarkers, only leptin showed an interesting diagnostic performance with an AUC of 0.781, at a cut-off value of 2.11 ng/mL, demonstrating a sensitivity of 78%, a specificity of 77% and a positive predictive value of 85%. Main limitations of our study are the exploratory design and the criteria adopted for patients' selection determining a detection rate for prostate cancer above the usual range. Leptin only, in our preliminary study, shows promising diagnostic accuracy for the selection of patients candidate to prostate biopsy. Further studies are required to confirm its diagnostic value and its relation with BMI.

  9. Biomarkers of human exposure to personal care products: results from the Flemish Environment and Health Study (FLEHS 2007-2011).

    Science.gov (United States)

    Den Hond, Elly; Paulussen, Melissa; Geens, Tinne; Bruckers, Liesbeth; Baeyens, Willy; David, Frank; Dumont, Emmie; Loots, Ilse; Morrens, Bert; de Bellevaux, Benoit Nemery; Nelen, Vera; Schoeters, Greet; Van Larebeke, Nicolas; Covaci, Adrian

    2013-10-01

    Personal care products (PCPs), such as soaps, perfumes, cosmetics, lotions, etc., contain a variety of chemicals that have been described as potentially hormone disrupting chemicals. Therefore, it is important to assess the internal exposure of these chemicals in humans. Within the 2nd Flemish Environment and Health Study (FLEHS II, 2007-2011), the human exposure to three classes of pollutants that are present in a wide variety of PCPs--i.e. polycyclic musks (galaxolide, HHCB and tonalide, AHTN in blood), parabens (urinary para-hydroxybenzoic acid, HBA) and triclosan (urinary TCS)--was assessed in 210 Flemish adolescents (14-15 years) and in 204 adults (20-40 years) randomly selected from the general population according to a stratified two stage clustered study design. The aim of this study was to define average levels of exposure in the general Flemish population and to identify determinants of exposure. Average levels (GM (95% CI)) in the Flemish adolescents were 0.717 (0.682-0.753) μg/L for blood HHCB; 0.118 (0.108-0.128) μg/L for blood AHTN; 1022 (723-1436) μg/L for urinary HBA and 2.19 (1.64-2.92) μg/L for urinary TCS. In the adults, levels of HBA were on average 634 (471-970) μg/L. Inter-individual variability was small for HHCB and AHTN, intermediate for HBA, and large for TCS. All biomarkers were positively associated with the use of PCPs. Additionally, levels of HHCB and AHTN increased with higher educational level of the adolescents. Both in adults and adolescents, urinary HBA levels were negatively correlated with BMI. We define here Flemish exposure values for biomarkers of PCPs, which can serve as baseline exposure levels to identify exposure trends in future biomonitoring campaigns.

  10. Human genotoxic study carried out two years after oil exposure during the clean-up activities using two different biomarkers.

    NARCIS (Netherlands)

    Biern, G.; Giraldo, J.; Zock, J.P.; Monyarch, G.; Espinosa, A.; Rodríguez-Trigo, G.; Gomez, F.; Pozo-Rodríguez, F.; Barberà, J.A.; Fuster, C.

    2015-01-01

    Micronuclei, comet and chromosome alterations assays are the most widely used biomarkers for determining the genotoxic damage in a population exposed to genotoxic chemicals. While chromosome alterations are an excellent biomarker to detect short- and long-term genotoxic effects, the comet assay only

  11. An integrated approach to study the biomarker responses in marine gastropod Nerita chamaeleon environmentally exposed to polycyclic aromatic hydrocarbons

    Digital Repository Service at National Institute of Oceanography (India)

    Bhagat, J.; Sarkar, A.; Deepti, V.; Singh, V.; Raiker, L.; Ingole, B.S.

    from 5.29 - 12.14 μg/g wet weight. Standardized values of biomarker response were visualized using star plots, which show unique patterns for different biomarkers. The mean IBR value was found to be highest at Dona Paula (8.07 ± 0.91) followed...

  12. MicroRNAs as Biomarkers for Acute Atrial Remodeling in Marathon Runners (The miRathon Study--A Sub-Study of the Munich Marathon Study.

    Directory of Open Access Journals (Sweden)

    Sebastian Clauss

    Full Text Available Physical activity is beneficial for individual health, but endurance sport is associated with the development of arrhythmias like atrial fibrillation. The underlying mechanisms leading to this increased risk are still not fully understood. MicroRNAs are important mediators of proarrhythmogenic remodeling and have potential value as biomarkers in cardiovascular diseases. Therefore, the objective of our study was to determine the value of circulating microRNAs as potential biomarkers for atrial remodeling in marathon runners (miRathon study.30 marathon runners were recruited into our study and were divided into two age-matched groups depending on the training status: elite (ER, ≥55 km/week, n = 15 and non-elite runners (NER, ≤40 km/week, n = 15. All runners participated in a 10 week training program before the marathon. MiRNA plasma levels were measured at 4 time points: at baseline (V1, after a 10 week training period (V2, immediately after the marathon (V3 and 24h later (V4. Additionally, we obtained clinical data including serum chemistry and echocardiography at each time point.MiRNA plasma levels were similar in both groups over time with more pronounced changes in ER. After the marathon miR-30a plasma levels increased significantly in both groups. MiR-1 and miR-133a plasma levels also increased but showed significant changes in ER only. 24h after the marathon plasma levels returned to baseline. MiR-26a decreased significantly after the marathon in elite runners only and miR-29b showed a non-significant decrease over time in both groups. In ER miRNA plasma levels showed a significant correlation with LA diameter, in NER miRNA plasma levels did not correlate with echocardiographic parameters.MiRNAs were differentially expressed in the plasma of marathon runners with more pronounced changes in ER. Plasma levels in ER correlate with left atrial diameter suggesting that circulating miRNAs could potentially serve as biomarkers of atrial

  13. MicroRNAs as Biomarkers for Acute Atrial Remodeling in Marathon Runners (The miRathon Study – A Sub-Study of the Munich Marathon Study)

    Science.gov (United States)

    Hildebrand, Bianca; Kääb, Stefan; Hoster, Eva; Klier, Ina; Martens, Eimo; Hanley, Alan; Hanssen, Henner; Halle, Martin; Nickel, Thomas

    2016-01-01

    Introduction Physical activity is beneficial for individual health, but endurance sport is associated with the development of arrhythmias like atrial fibrillation. The underlying mechanisms leading to this increased risk are still not fully understood. MicroRNAs are important mediators of proarrhythmogenic remodeling and have potential value as biomarkers in cardiovascular diseases. Therefore, the objective of our study was to determine the value of circulating microRNAs as potential biomarkers for atrial remodeling in marathon runners (miRathon study). Methods 30 marathon runners were recruited into our study and were divided into two age-matched groups depending on the training status: elite (ER, ≥55 km/week, n = 15) and non-elite runners (NER, ≤40 km/week, n = 15). All runners participated in a 10 week training program before the marathon. MiRNA plasma levels were measured at 4 time points: at baseline (V1), after a 10 week training period (V2), immediately after the marathon (V3) and 24h later (V4). Additionally, we obtained clinical data including serum chemistry and echocardiography at each time point. Results MiRNA plasma levels were similar in both groups over time with more pronounced changes in ER. After the marathon miR-30a plasma levels increased significantly in both groups. MiR-1 and miR-133a plasma levels also increased but showed significant changes in ER only. 24h after the marathon plasma levels returned to baseline. MiR-26a decreased significantly after the marathon in elite runners only and miR-29b showed a non-significant decrease over time in both groups. In ER miRNA plasma levels showed a significant correlation with LA diameter, in NER miRNA plasma levels did not correlate with echocardiographic parameters. Conclusion MiRNAs were differentially expressed in the plasma of marathon runners with more pronounced changes in ER. Plasma levels in ER correlate with left atrial diameter suggesting that circulating miRNAs could potentially serve

  14. Plasma elaidic acid level as biomarker of industrial trans fatty acids and risk of weight change : Report from the EPIC study

    NARCIS (Netherlands)

    Chajès, Véronique; Biessy, Carine; Ferrari, Pietro; Romieu, Isabelle; Freisling, Heinz; Huybrechts, Inge; Scalbert, Augustin; Bueno De Mesquita, Bas; Romaguera, Dora; Gunter, Marc J.; Vineis, Paolo; Hansen, Camilla Plambeck; Jakobsen, Marianne Uhre; Clavel-Chapelon, Franc¸oise; Fagherazzi, Guy; Boutron-Ruault, Marie Christine; Katzke, Verana; Neamat-Allah, Jasmine; Boeing, Heiner; Bachlechner, Ursula; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Pala, Valeria; Masala, Giovanna; Mattiello, Amalia; Skeie, Guri; Weiderpass, Elisabete; Agudo, Antonio; Huerta, Jose Maria; Ardanaz, Eva; Sánchez, Maria Jose; Dorronsoro, Miren; Quirós, Jose Ramon; Johansson, Ingegerd; Winkvist, Anna; Sonested, Emily; Key, Tim; Khaw, Kay Tee; Wareham, Nicolas J.; Peeters, Petra H M; Slimani, Nadia

    2015-01-01

    Background: Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change

  15. Socioeconomic factors are associated with folate and vitamin B12 intakes and related biomarkers concentrations in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence study

    NARCIS (Netherlands)

    Iglesia, I.; Mouratidou, Th.; González, M.; Novakovic, R.N.; Breidenassel, C.; Jiménez-Pavón, D.; Huybrechts, I.; Geelen, A.; Veer, van 't P.; Cavelaars, A.J.E.M.

    2014-01-01

    Because socioeconomic factors (SEFs) may influence dietary quality and vitamin intakes, this study aimed to examine associations between socioeconomic factors and folate and vitamin B12 intakes as well as their related biomarkers in the Healthy Lifestyle in Europe by Nutrition in Adolescence study.

  16. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  17. 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.

  18. Ecotoxicological assessment of tannery effluent using guppy fish (Poecilia reticulata) as an experimental model: a biomarker study.

    Science.gov (United States)

    Aich, Anulipi; Goswami, Abhishek Roy; Roy, Utpal Singha; Mukhopadhyay, Subhra Kumar

    2015-01-01

    Tannery wastewater in the East Calcutta Wetlands (a Ramsar site of West Bengal; number 1208) exerts adverse effects on commercial fish production and subsequently affects humans. The present study was conducted to investigate acute and chronic toxicity of tannery effluent on a fish biosystem by examining oxidative stress enzyme expression in different organs including liver, gills, and muscle following exposure. Phosphatases, both alkaline phosphatase and acid phosphatase, and antioxidant superoxide dismutase and catalase enzyme activities were determined in guppy fish (Poecilia reticulata) exposed to sublethal concentrations of composite tannery effluent. Data demonstrated that tannery effluent was capable of interfering with metabolic processes of fish by altering stress enzyme activities in fish organs, resulting in cellular injury. Data suggest that elevated activities of stress enzymes in fish upon exposure to environmental pollutants may serve as important biomarkers for oxidative stress.

  19. MicroRNAs are suitable for assessment as biomarkers from formalin-fixed paraffin-embedded tissue, and miR-24 represents an appropriate reference microRNA for diffuse large B-cell lymphoma studies.

    Science.gov (United States)

    Culpin, Rachel Emily; Sieniawski, Michal; Proctor, Stephen John; Menon, Geetha; Mainou-Fowler, Tryfonia

    2013-03-01

    Tissue biopsy specimens in the form of formalin-fixed paraffin-embedded tissue (FFPET) represent a valuable resource for biomarker identification and validation. However, to date, they remain an underused asset due to uncertainty regarding RNA extraction and the reliability of downstream techniques, including quantitative RT-PCR. Recently, much interest has emerged in the study of microRNAs; small single-stranded RNAs with a role in transcriptional regulation, that are thought to be well preserved in FFPET. In this study, we show that microRNA expression is comparable between FFPET and matched fresh-frozen samples (miR-17-5p: p=0.01, miR-92: p=0.003), and demonstrate that no significant deterioration in expression occurs over prolonged FFPET storage (p=0.06). Furthermore, microRNA expression is equivalent dependant on RNA extraction method (pmicroRNA for diffuse large B-cell lymphoma (DLBCL) FFPET studies.

  20. A biomarker panel (Bioscore incorporating monocytic surface and soluble TREM-1 has high discriminative value for ventilator-associated pneumonia: a prospective observational study.

    Directory of Open Access Journals (Sweden)

    Vimal Grover

    Full Text Available Ventilator-associated pneumonia (VAP increases mortality in critical illness. However, clinical diagnostic uncertainty persists. We hypothesised that measuring cell-surface and soluble inflammatory markers, incorporating Triggering Receptor Expressed by Myeloid cells (TREM-1, would improve diagnostic accuracy.A single centre prospective observational study, set in a University Hospital medical-surgical intensive Care unit, recruited 91 patients into 3 groups: 27 patients with VAP, 33 ventilated controls without evidence of pulmonary sepsis (non-VAP, and 31 non-ventilated controls (NVC, without clinical infection, attending for bronchoscopy. Paired samples of Bronchiolo-alveolar lavage fluid (BALF and blood from each subject were analysed for putative biomarkers of infection: Cellular (TREM-1, CD11b and CD62L and soluble (IL-1β, IL-6, IL-8, sTREM-1, Procalcitonin. Expression of cellular markers on monocytes and neutrophils were measured by flow cytometry. Soluble inflammatory markers were determined by ELISA. A biomarker panel ('Bioscore', was constructed, tested and validated, using Fisher's discriminant function analysis, to assess its value in distinguishing VAP from non VAP.The expression of TREM-1 on monocytes (mTREM-1 and neutrophils (nTREM-1 and concentrations of IL-1β, IL-8, and sTREM-1 in BALF were significantly higher in VAP compared with non-VAP and NVC (p<0.001. The BALF/blood mTREM-1 was significantly higher in VAP patients compared to non-VAP and NVC (0.8 v 0.4 v 0.3 p<0.001. A seven marker Bioscore (BALF/blood ratio mTREM-1 and mCD11b, BALF sTREM-1, IL-8 and IL-1β, and serum CRP and IL-6 correctly identified 88.9% of VAP cases and 100% of non-VAP cases.A 7-marker bioscore, incorporating cellular and soluble TREM-1, accurately discriminates VAP from non-pulmonary infection.

  1. The use of a lacertid lizard as a model for reptile ecotoxicology studies: part 2--biomarkers of exposure and toxicity among pesticide exposed lizards.

    Science.gov (United States)

    Amaral, Maria José; Bicho, Rita C; Carretero, Miguel A; Sanchez-Hernandez, Juan C; Faustino, Augusto M R; Soares, Amadeu M V M; Mann, Reinier M

    2012-05-01

    As part of a wider study examining the impacts of corn pesticides on lacertid lizards in north-western Portugal, we examined various physiological, biochemical, and histological biomarkers of exposure and effect among field populations of Podarcis bocagei. Biomarkers included body condition index, standard metabolic rate, locomotor performance, parasitization, glutathione oxidative pathways and related enzyme activity, lipid peroxidation and liver and testis histology. Few of the various biomarkers investigated provided statistically significant evidence of toxic effect. However, using a weight of evidence approach, we conclude that pesticides are affecting lizards living in the vicinity of pesticide exposed corn agriculture sites. Lizards from these locations present a profile of animals under metabolic stress with reduced condition indices, increased standard metabolic rate, lower incidence of hepatocyte vacuolation, altered iron metabolism, increased activation of GSH oxidation pathways, and even increased prevalence of hemoparasites.

  2. Looking for new biomarkers of skin wound vitality with a cytokine-based multiplex assay: preliminary study.

    Science.gov (United States)

    Peyron, Pierre-Antoine; Baccino, Éric; Nagot, Nicolas; Lehmann, Sylvain; Delaby, Constance

    2017-02-01

    Determination of skin wound vitality is an important issue in forensic practice. No reliable biomarker currently exists. Quantification of inflammatory cytokines in injured skin with MSD(®) technology is an innovative and promising approach. This preliminary study aims to develop a protocol for the preparation and the analysis of skin samples. Samples from ante mortem wounds, post mortem wounds, and intact skin ("control samples") were taken from corpses at the autopsy. After an optimization of the pre-analytical protocol had been performed in terms of skin homogeneisation and proteic extraction, the concentration of TNF-α was measured in each sample with the MSD(®) approach. Then five other cytokines of interest (IL-1β, IL-6, IL-10, IL-12p70 and IFN-γ) were simultaneously quantified with a MSD(®) multiplex assay. The optimal pre-analytical conditions consist in a proteic extraction from a 6 mm diameter skin sample, in a PBS buffer with triton 0,05%. Our results show the linearity and the reproductibility of the TNF-α quantification with MSD(®), and an inter- and intra-individual variability of the concentrations of proteins. The MSD(®) multiplex assay is likely to detect differential skin concentrations for each cytokine of interest. This preliminary study was used to develop and optimize the pre-analytical and analytical conditions of the MSD(®) method using injured and healthy skin samples, for the purpose of looking for and identifying the cytokine, or the set of cytokines, that may be biomarkers of skin wound vitality.

  3. Effects of phytoestrogen genistein on cytogenetic biomarkers in postmenopausal women: 1 year randomized, placebo-controlled study.

    Science.gov (United States)

    Atteritano, Marco; Pernice, Francesco; Mazzaferro, Susanna; Mantuano, Stefania; Frisina, Alessia; D'Anna, Rosario; Cannata, Maria Letizia; Bitto, Alessandra; Squadrito, Francesco; Frisina, Nicola; Buemi, Michele

    2008-07-28

    To evaluate in a twelve-month, randomized placebo-controlled study whether pure administration of phytoestrogen genistein (54 mg/day) might reduce cytogenetic biomarkers in peripheral lymphocytes of postmenopausal women. A total of 57 postmenopausal women met the criteria and were randomly assigned to receive phytoestrogen genistein (n = 30) or placebo (n = 27). There was no significant difference in age, length of time since menopause or body mass index between the two groups. After one year, plasma genistein level was 0.14 +/- 0.01 micromol/L in the control group and 0.72 +/- 0.08 micromol/L in the genistein group (P < 0.0001). At baseline, sister chromatid exchange rate was 4.97 +/- 2.17 in the control group and 4.96 +/- 1.83 in the genistein group (P = 0.89). After one year, sister chromatid exchange rate was 4.96 +/- 2.16 in the control group and 3.98 +/- 1.14 in the genistein group (P < 0.05). High frequency cells count was 3% in the genistein group and 5% in the control group (P < 0.05) at the end of the study. Chromosomal aberration frequency was 5.55% in the control group at time 0 and 5.75% in the genistein group; after one year, the figures were 5.86% in the control group and 4.5% in the genistein group (P < 0.05). After one year, there was a negative relationship between sister chromatid exchange rate and plasma levels (r = - 0.43; P < 0.05) in the genistein group. Phytoestrogen genistein has been shown in postmenopausal women to be effective in the reduction of cytogenetic biomarkers. The protective effect on genomic damage appears to be a particularly promising tool in reducing the risk of cancer.

  4. Correlation of perfusion MRI and 18F-FDG PET imaging biomarkers for monitoring regorafenib therapy in experimental colon carcinomas with immunohistochemical validation.

    Directory of Open Access Journals (Sweden)

    Ralf S Eschbach

    Full Text Available To investigate a multimodal, multiparametric perfusion MRI / 18F-fluoro-deoxyglucose-(18F-FDG-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation.Human colorectal adenocarcinoma xenografts (HT-29 were implanted subcutaneously in n = 17 (n = 10 therapy group; n = 7 control group female athymic nude rats (Hsd:RH-Foxn1rnu. Animals were imaged at baseline and after a one-week daily treatment protocol with regorafenib (10 mg/kg bodyweight using a multimodal, multiparametric perfusion MRI/18F-FDG-PET imaging protocol. In perfusion MRI, quantitative parameters of plasma flow (PF, mL/100 mL/min, plasma volume (PV, % and endothelial permeability-surface area product (PS, mL/100 mL/min were calculated. In 18F-FDG-PET, tumor-to-background-ratio (TTB was calculated. Perfusion MRI parameters were correlated with TTB and immunohistochemical assessments of tumor microvascular density (CD-31 and cell proliferation (Ki-67.Regorafenib significantly (p<0.01 suppressed PF (81.1±7.5 to 50.6±16.0 mL/100mL/min, PV (12.1±3.6 to 7.5±1.6% and PS (13.6±3.2 to 7.9±2.3 mL/100mL/min as well as TTB (3.4±0.6 to 1.9±1.1 between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03 lower tumor microvascular density (CD-31, 7.0±2.4 vs. 16.1±5.9 and tumor cell proliferation (Ki-67, 434.0 ± 62.9 vs. 663.0 ± 98.3 in the therapy group. Perfusion MRI parameters ΔPF, ΔPV and ΔPS showed strong and significant (r = 0.67-0.78; p<0.01 correlations to the PET parameter ΔTTB and significant correlations (r = 0.57-0.67; p<0.03 to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55; p<0.05.A multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and 18F

  5. Iron and Oxidative Stress in Parkinson's Disease: An Observational Study of Injury Biomarkers.

    Directory of Open Access Journals (Sweden)

    Marcio S Medeiros

    Full Text Available Parkinson's disease (PD is characterized by progressive motor impairment attributed to progressive loss of dopaminergic neurons in the substantia nigra (SN pars compacta. In addition to an accumulation of iron, there is also an increased production of reactive oxygen/nitrogen species (ROS/RNS and inflammatory markers. These observations suggest that iron dyshomeostasis may be playing a key role in neurodegeneration. However, the mechanisms underlying this metal-associated oxidative stress and neuronal damage have not been fully elucidated. To determine peripheral levels of iron, ferritin, and transferrin in PD patients and its possible relation with oxidative/nitrosative parameters, whilst attempting to identify a profile of peripheral biomarkers in this neurological condition. Forty PD patients and 46 controls were recruited to compare serum levels of iron, ferritin, transferrin, oxidative stress markers (superoxide dismutase (SOD, catalase (CAT, nitrosative stress marker (NOx, thiobarbituric acid reactive substances (TBARS, non-protein thiols (NPSH, advanced oxidation protein products (AOPP, ferric reducing ability of plasma (FRAP and vitamin C as well as inflammatory markers (NTPDases, ecto-5'-nucleotidase, adenosine deaminase (ADA, ischemic-modified albumin (IMA and myeloperoxidase. Iron levels were lower in PD patients, whereas there was no difference in ferritin and transferrin. Oxidative stress (TBARS and AOPP and inflammatory markers (NTPDases, IMA, and myeloperoxidase were significantly higher in PD, while antioxidants FRAP, vitamin C, and non-protein thiols were significantly lower in PD. The enzymes SOD, CAT, and ecto-5'-nucleotidase were not different among the groups, although NOx and ADA levels were significantly higher in the controls. Our data corroborate the idea that ROS/RNS production and neuroinflammation may dysregulate iron homeostasis and collaborate to reduce the periphery levels of this ion, contributing to alterations

  6. Iron and Oxidative Stress in Parkinson's Disease: An Observational Study of Injury Biomarkers.

    Science.gov (United States)

    Medeiros, Marcio S; Schumacher-Schuh, Arthur; Cardoso, Andreia Machado; Bochi, Guilherme Vargas; Baldissarelli, Jucimara; Kegler, Aline; Santana, Daniel; Chaves, Carolina Maria Martins Behle Soares; Schetinger, Maria Rosa Chitolina; Moresco, Rafael Noal; Rieder, Carlos R M; Fighera, Michele Rechia

    2016-01-01

    Parkinson's disease (PD) is characterized by progressive motor impairment attributed to progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. In addition to an accumulation of iron, there is also an increased production of reactive oxygen/nitrogen species (ROS/RNS) and inflammatory markers. These observations suggest that iron dyshomeostasis may be playing a key role in neurodegeneration. However, the mechanisms underlying this metal-associated oxidative stress and neuronal damage have not been fully elucidated. To determine peripheral levels of iron, ferritin, and transferrin in PD patients and its possible relation with oxidative/nitrosative parameters, whilst attempting to identify a profile of peripheral biomarkers in this neurological condition. Forty PD patients and 46 controls were recruited to compare serum levels of iron, ferritin, transferrin, oxidative stress markers (superoxide dismutase (SOD), catalase (CAT), nitrosative stress marker (NOx), thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP) and vitamin C) as well as inflammatory markers (NTPDases, ecto-5'-nucleotidase, adenosine deaminase (ADA), ischemic-modified albumin (IMA) and myeloperoxidase). Iron levels were lower in PD patients, whereas there was no difference in ferritin and transferrin. Oxidative stress (TBARS and AOPP) and inflammatory markers (NTPDases, IMA, and myeloperoxidase) were significantly higher in PD, while antioxidants FRAP, vitamin C, and non-protein thiols were significantly lower in PD. The enzymes SOD, CAT, and ecto-5'-nucleotidase were not different among the groups, although NOx and ADA levels were significantly higher in the controls. Our data corroborate the idea that ROS/RNS production and neuroinflammation may dysregulate iron homeostasis and collaborate to reduce the periphery levels of this ion, contributing to alterations

  7. Clinical trial designs for testing biomarker-based personalized therapies

    Science.gov (United States)

    Lai, Tze Leung; Lavori, Philip W; Shih, Mei-Chiung I; Sikic, Branimir I

    2014-01-01

    Background Advances in molecular therapeutics in the past decade have opened up new possibilities for treating cancer patients with personalized therapies, using biomarkers to determine which treatments are most likely to benefit them, but there are difficulties and unresolved issues in the development and validation of biomarker-based personalized therapies. We develop a new clinical trial design to address some of these issues. The goal is to capture the strengths of the frequentist and Bayesian approaches to address this problem in the recent literature and to circumvent their limitations. Methods We use generalized likelihood ratio tests of the intersection null and enriched strategy null hypotheses to derive a novel clinical trial design for the problem of advancing promising biomarker-guided strategies toward eventual validation. We also investigate the usefulness of adaptive randomization (AR) and futility stopping proposed in the recent literature. Results Simulation studies demonstrate the advantages of testing both the narrowly focused enriched strategy null hypothesis related to validating a proposed strategy and the intersection null hypothesis that can accommodate to a potentially successful strategy. AR and early termination of ineffective treatments offer increased probability of receiving the preferred treatment and better response rates for patients in the trial, at the expense of more complicated inference under small-to-moderate total sample sizes and some reduction in power. Limitations The binary response used in the development phase may not be a reliable indicator of treatment benefit on long-term clinical outcomes. In the proposed design, the biomarker-guided strategy (BGS) is not compared to ‘standard of care’, such as physician’s choice that may be informed by patient characteristics. Therefore, a positive result does not imply superiority of the BGS to ‘standard of care’. The proposed design and tests are valid asymptotically

  8. Proximal tubule dysfunction is associated with podocyte damage biomarkers nephrin and vascular endothelial growth factor in type 2 diabetes mellitus patients: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Ligia Petrica

    growth factor processing in early diabetic nephropathy, a fact which could be related to advanced glycation end-products intervention. Podocyte damage and proximal tubule dysfunction biomarkers could be validated as a practical approach to the diagnosis of early diabetic nephropathy by further studies on larger cohorts.

  9. 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 Rott