Sample records for biomarker developmental laboratories

  1. Thinking clearly about the endophenotype-intermediate phenotype-biomarker distinctions in developmental psychopathology research. (United States)

    Lenzenweger, Mark F


    The endophenotype is central to modern developmental psychopathology studies. It is used in studies seeking to connect the genetic substrates of the panoply of major mental disorders with processes, tapped by laboratory and other assessment measures, in the genotype to a behavior/psychopathology pathway. Proposed originally by Gottesman and Shields (1972; Shields & Gottesman, 1973) 41 years ago, the endophenotype concept has gained widespread traction in psychopathology research since the Gottesman and Gould (2003) review. Other concepts broadly related to the endophenotype notion have also generated discussion in experimental and developmental psychopathology research. One is the intermediate phenotype, a concept proffered as a putative alternative formulation to the endophenotype. Another concept in this intellectual vein is biomarker. The terms endophenotype, intermediate phenotype, and biomarker have often been used interchangeably in the psychiatric literature, yielding conceptual confusion. However, these three terms are not fungible. The recent Research Domain Criteria proposal from the National Institute of Mental Health has emphasized selected underlying processes thought to be of developmental etiologic significance to psychopathology. These selected processes will be the focus of energetic future research efforts, many of which will make use of the endophenotype and biomarker research paradigms. In this context, the concepts of endophenotype, intermediate phenotype, and biomarker are examined critically and contrasted in terms of meaning, intention, clarity, and intellectual history. This analysis favors use of the endophenotype concept in genetically informed laboratory and neuroscience studies of psychopathology. The term intermediate phenotype is perhaps best restricted to its originally defined meaning in genetics. Biomarker is used to denote objectively measured biological antecedents or consequences of normal or pathogenic processes or a

  2. Laboratory detection of sepsis: biomarkers and molecular approaches. (United States)

    Riedel, Stefan; Carroll, Karen C


    Sepsis, severe sepsis, and septic shock cause significant morbidity and mortality worldwide. Rapid diagnosis and therapeutic interventions are desirable to improve the overall mortality in patients with sepsis. However, gold standard laboratory diagnostic methods for sepsis, pose a significant challenge to rapid diagnosis of sepsis by physicians and laboratories. This article discusses the usefulness and potential of biomarkers and molecular test methods for a more rapid clinical and laboratory diagnosis of sepsis. Because new technologies are quickly emerging, physicians and laboratories must appreciate the key factors and characteristics that affect the clinical usefulness and diagnostic accuracy of these test methodologies.

  3. Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories. (United States)

    Kim, Kyuri; Chini, Naseem; Fairchild, David G; Engle, Steven K; Reagan, William J; Summers, Sandra D; Mirsalis, Jon C


    There is a great need for improved diagnostic and prognostic accuracy of potential cardiac toxicity in drug development. This study reports the evaluation of several commercially available biomarker kits by 3 institutions (SRI, Eli Lilly, and Pfizer) for the discrimination between myocardial degeneration/necrosis and cardiac hypertrophy as well as the assessment of the interlaboratory and interplatform variation in results. Serum concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide [NT-proANP] and N-terminal pro-brain natriuretic peptide [NT-proBNP]), cardiac and skeletal troponins (cTnI, cTnT, and sTnI), myosin light chain 3 (Myl3), and fatty acid binding protein 3 (FABP3) were assessed in rats treated with minoxidil (MNX) and isoproterenol (ISO). MNX caused increased heart-to-body weight ratios and prominent elevations in NT-proANP and NT-proBNP concentrations detected at 24-hr postdose without elevation in troponins, Myl3, or FABP3 and with no abnormal histopathological findings. ISO caused ventricular leukocyte infiltration, myocyte fibrosis, and necrosis with increased concentrations of the natriuretic peptides, cardiac troponins, and Myl3. These results reinforce the advantages of a multimarker strategy in elucidating the underlying cause of cardiac insult and detecting myocardial tissue damage at 24-hr posttreatment. The interlaboratory and interplatform comparison analyses also showed that the data obtained from different laboratories and platforms are highly correlated and reproducible, making these biomarkers widely applicable in preclinical studies.

  4. Identification of Novel Epithelial Ovarian Cancer Biomarkers by Cross-laboratory Microarray Analysis

    Institute of Scientific and Technical Information of China (English)

    蒋学锋; 朱涛; 杨洁; 李双; 叶双梅; 廖书杰; 孟力; 卢运萍; 马丁


    The purpose of this study was to pool information in epithelial ovarian cancer by combining studies using Affymetrix expression microarray datasets made at different laboratories to identify novel biomarkers.Epithelial microarray expression information across laboratories was screened and combined after preprocessing raw microarray data,then ANOVA and unpaired T test statistical analysis was performed for identifying differentially expressed genes(DEGs),followed by clustering and pathway analysis for these ...


    Directory of Open Access Journals (Sweden)

    E. N. Aleksandrova


    Full Text Available Laboratory medicine in the early 21st century has achieved advances due to the development and prompt practical introduction of innovative molecular cell technologies, which have assisted in increasing the diagnostic sensitivity and specificity of laboratory tests and in substantially expanding the spectrum of study biomarkers in rheumatology. High-technology automated analytical systems using both classical uniplex methods for immunochemical analysis (indirect immunofluorescence test, enzyme immunoassay, immunoblotting, immunodot assay, immunonephelometry, chemiluminescence immunoassay, and radioimmunoassay and multiplex diagnostic platforms based on DNA, RNA, protein and cellular microchips, polymerase chain reaction, flow cytometry, and mass spectrometry have been used in the past decade to determine biomarkers of rheumatic diseases (RD in blood, synovial fluid, urine, biopsy specimens of the synovial membrane, kidney, and other affected tissues.Present-day generation of molecular and cellular biomarkers (autoantibodies, acute-phase inflammatory proteins, cytokines, chemokines, vascular endothelial activation markers, immunoglobulins, complement components, lymphocyte subpopulations, osseous and cartilaginous tissue metabolic products, intracellular signaling molecules, proteases, and genetic, epigenetic, and transcriptomic markers is an important tool for prevention, early diagnosis, assessment of disease activity, progression rate, clinical laboratory subtypes of RD, prediction of the efficiency of therapy and the risk of adverse events during treatment. Deciphering of the key pathogenetic mechanisms of RD could identify the molecular and cellular biomarkers that might be used as therapeutic targets. Biologicals (monoclonal antibodies and hybrid protein molecules that selectively inhibit proinflammatory cytokines and membrane molecules mediating the pathological activation of immunocompetent cells are successfully used to treat RD today

  6. Metabolomics approach reveals metabolic disorders and potential biomarkers associated with the developmental toxicity of tetrabromobisphenol A and tetrachlorobisphenol A (United States)

    Ye, Guozhu; Chen, Yajie; Wang, Hong-Ou; Ye, Ting; Lin, Yi; Huang, Qiansheng; Chi, Yulang; Dong, Sijun


    Tetrabromobisphenol A and tetrachlorobisphenol A are halogenated bisphenol A (H-BPA), and has raised concerns about their adverse effects on the development of fetuses and infants, however, the molecular mechanisms are unclear, and related metabolomics studies are limited. Accordingly, a metabolomics study based on gas chromatography-mass spectrometry was employed to elucidate the molecular developmental toxicology of H-BPA using the marine medaka (Oryzias melastigmas) embryo model. Here, we revealed decreased synthesis of nucleosides, amino acids and lipids, and disruptions in the TCA (tricarboxylic acid) cycle, glycolysis and lipid metabolism, thus inhibiting the developmental processes of embryos exposed to H-BPA. Unexpectedly, we observed enhanced neural activity accompanied by lactate accumulation and accelerated heart rates due to an increase in dopamine pathway and a decrease in inhibitory neurotransmitters following H-BPA exposure. Notably, disorders of the neural system, and disruptions in glycolysis, the TCA cycle, nucleoside metabolism, lipid metabolism, glutamate and aspartate metabolism induced by H-BPA exposure were heritable. Furthermore, lactate and dopa were identified as potential biomarkers of the developmental toxicity of H-BPA and related genetic effects. This study has demonstrated that the metabolomics approach is a useful tool for obtaining comprehensive and novel insights into the molecular developmental toxicity of environmental pollutants.


    Directory of Open Access Journals (Sweden)

    A. A. Novikov


    Full Text Available The key component in the management of patients with rheumatoid arthritis (RA is regular control of RA activity. The quantitative assessment of a patient’s status allows the development of standardized indications for anti-rheumatic therapy.Objective: to identify the laboratory biomarkers able to reflect RA activity.Subjects and methods. Fifty-eight patients with RA and 30 age- and sex-matched healthy donors were examined. The patients were divided into high/moderate and mild disease activity groups according to DAS28. The serum concentrations of 30 biomarkers were measured using immunonephelometric assay, enzyme immunoassay, and xMAP technology.Results and discussion. Multivariate analysis could identify the factors mostly related to high/moderate RA activity according to DAS28, such as fibroblast growth factor-2, monocyte chemoattractant protein-1, interleukins (IL 1α, 6, and 15, and tumor necrosis factor-α and could create a prognostic model for RA activity assessment. ROC analysis has shown that this model has excellent diagnostic efficiency in differentiating high/moderate versus low RA activity.Conclusion. To create a subjective assessment-independent immunological multiparameter index of greater diagnostic accuracy than the laboratory parameters routinely used in clinical practice may be a qualitatively new step in assessing and monitoring RA activity.

  8. Inter-laboratory assessment of a harmonized zebrafish developmental toxicology assay - progress report on phase I. (United States)

    Gustafson, A-L; Stedman, D B; Ball, J; Hillegass, J M; Flood, A; Zhang, C X; Panzica-Kelly, J; Cao, J; Coburn, A; Enright, B P; Tornesi, M B; Hetheridge, M; Augustine-Rauch, K A


    This report provides a progress update of a consortium effort to develop a harmonized zebrafish developmental toxicity assay. Twenty non-proprietary compounds (10 animal teratogens and 10 animal non-teratogens) were evaluated blinded in 4 laboratories. Zebrafish embryos from pond-derived and cultivated strain wild types were exposed to the test compounds for 5 days and subsequently evaluated for lethality and morphological changes. Each of the testing laboratories achieved similar overall concordance to the animal data (60-70%). Subsequent optimization procedures to improve the overall concordance focused on compound formulation and test concentration adjustments, chorion permeation and number of replicates. These optimized procedures were integrated into a revised protocol and all compounds were retested in one lab using embryos from pond-derived zebrafish and achieved 85% total concordance. To further assess assay performance, a study of additional compounds is currently in progress at two laboratories using embryos from pond-derived and cultivated-strain wild type zebrafish.

  9. A review of reproductive and developmental toxicity of silver nanoparticles in laboratory animals. (United States)

    Ema, Makoto; Okuda, Hirokazu; Gamo, Masashi; Honda, Kazumasa


    We summarized significant effects reported in the literature on the reproductive and developmental toxicity of silver nanoparticles (AgNPs) in laboratory animals. AgNPs showed testicular/sperm toxicity in males and ovarian and embryonic toxicity in females. Maternal injection of AgNPs delayed physical development and impaired cognitive behavior in offspring. Ag was accumulated in the testes after administration of AgNPs. AgNPs were identified in the visceral yolk sac after administration during early gestation in mice. Radiolabeled AgNPs were detected in placenta, breast milk, and pre- and postnatal offspring after injection during late gestation in rats. Ag in the ionic form, and possibly also particles, was suggested to be bioavailable. Although this review provides initial information on the potential reproductive and developmental toxicity of AgNPs, data is still very limited. Further studies using state-of-the-art methodologies and the relevant routes and doses for human exposure are required.

  10. Developmental biology of Argas neghmei Kohls & Hoogstraal (Acari: Argasidae) under laboratory conditions. (United States)

    González-Acuña, Daniel; Vargas, Pamela; Ardiles, Karen; Parra, Luis; Guglielmone, Alberto


    In order to describe the developmental biology of the tick Argas neghmei Kohls & Hoogstraal under laboratory conditions, 40 females and 40 males were collected from chicken coops located in Calama (II Region, Chile). They were fed on chickens and maintained under two laboratory conditions: one group at 30 +/- 5 degrees C and 35 +/- 5 % RH and another at 27 +/- 5 degrees C and 80 +/- 5 % RH, both at 12: 12 h L:D photoperiod. The ticks were observed daily to determine larval feeding periods, preoviposition, oviposition, egg incubation as well as the frequency of egg laying, number of eggs laid, and percentage of larval hatching. Females did not lay eggs at 80 +/- 5% RH, and data on the biology of this tick was obtained only at 35 +/- 5% RH. The life cycle of A. neghmei lasted an average of 269 days. Feeding period of each nymphal stage as well as of adult females between oviposition events lasted less than a day. Females laid on average 1.8 egg batches and egg-laying period lasted on average 14 days, during which about 96 eggs were laid per female.

  11. An Inter-Laboratory Comparison for the Urinary Acrolein Biomarker 3-Hydroxypropyl-Mercapturic Acid (3-HPMA

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    Scherer Gerhard


    Full Text Available An inter-laboratory comparison study on the acrolein biomarker of exposure 3-hydroxypropyl-mercapturic acid (3-HPMA with 12 laboratories from 7 globally distributed countries was performed. The laboratories received coded triplicates of 4 spiked and lyophilized urine samples (LU, 12 samples as well as 5 authentic urine pool samples (PU, 15 samples covering the 3-HPMA concentration range from background (non-smoking to heavy smoking levels for analysis by using their own (in-house analytical method. All laboratories applied liquid chromatography with tandem mass spectrometry (LC-MS/MS, with most of them (10 of 12 using solid phase extraction (SPE as sample work-up procedure. The intra-laboratory variation (indicating repeatability was determined by calculating the standard deviation (sr and the coefficient of variation (CVr of the triplicates, whereas the inter-laboratory variation (indicating reproducibility was determined by calculating the standard deviation between laboratories (sR and the corresponding coefficient of variation (CVR. After removal of outlier samples or laboratories, the mean CVr values for LU and PU test samples ranged from 2.1–3.6% (mean: 2.8% and 2.4–3.7% (mean: 3.3%, respectively, indicating good repeatability for the determination of 3-HPMA in both sample types. CVR for LU and PU test samples ranged from 9.1–31.9% (mean: 18.8% and 13.9–27.0% (mean: 18.5%, respectively, indicating limited reproducibility in 3-HPMA analysis for both sample types. Re-calculation of the PU results by applying an embedded calibration (EC, derived from the reported peak areas for the LU test samples, somewhat improved the CVR values (range: 9.6–28.8%, mean: 16.7%.

  12. An integrated biomarker response index for the mussel Mytilus edulis based on laboratory exposure to anthracene and field transplantation experiments (United States)

    Yuan, Mengqi; Wang, You; Zhou, Bin; Jian, Xiaoyang; Dong, Wenlong; Tang, Xuexi


    Organic pollution is a serious environmental problem in coastal areas and it is important to establish quantitative methods for monitoring this pollution. This study screened a series of sensitive biomarkers to construct an integrated biomarker response (IBR) index using Mytilus edulis. Mussels were exposed to the polycyclic aromatic hydrocarbon anthracene under controlled laboratory conditions and the activities of components of the glutathione antioxidant system, and the concentrations of oxidative-damage markers, were measured in the gills and digestive glands. Anthracene exposure resulted in increased levels of malondialdehyde (MDA) and superoxide radicals (O{2/-}•), indicating that oxidative damage had occurred. Correspondingly, anthracene exposure induced increased activities of glutathione S -transferase (GST), glutathione peroxidase (GPx) and reduced glutathione (GSH) in digestive glands, and GPx and glutathione reductase (GR) in gills, consistent with stimulation of the antioxidant system. A field experiment was set up, in which mussels from a relatively clean area were transplanted to a contaminated site. One month later, the activities of GST, GPx and GR had increased in several tissues, particularly in the digestive glands. Based on the laboratory experiment, an IBR, which showed a positive relationship with anthracene exposure, was constructed. The IBR is suggested to be a potentially useful tool for assessing anthracene pollution.

  13. Integrated biomarker response index used in laboratory exposure of the mussel Mytilus edulis to water accommodated fractions of crude oil (United States)

    Yuan, Mengqi; Wang, You; Zhang, Xinxin; Hu, Shunxin; Tang, Xuexi


    Oil pollution is a serious environmental problem in coastal areas and to set up a quantitative evaluation method in monitoring the environmental pollution is of great importance. Individuals of Mytilus edulis, collected from the coastal area of Qingdao, were thus exposed to the water accommodated fractions (WAFs) of crude oil under controlled lab conditions. Mussels were exposed to different concentrations of WAFs for 96h acute toxicity experiment and 15d chronic toxicity experiment, a 7d restoration experiment was conducted after toxicity experiment as well. The activities of the antioxidant enzymes (CAT, GST, GPx and GR) were measured in gills of mussels. The purpose of the study was to screen out a series of sensitive biomarkers and set up an Integrated Biomarker Response index (IBR) for marine oil pollution monitoring. Results showed: (1) WAFs exposure induced the increased activities of CAT, GST, GPx and GR in gills, revealing a stimulation effect on the antioxidant system. Activities of enzymes were more significantly altered in response to higher concentrations of WAFs (2.3 and 5.0 mg.L-1) than lower concentrations (0.5 and 1.1 mg.L-1). After restoration experiment, the activities decreased to the initial levels. (2) IBR was set up base on the laboratory experiment, which showed a positive relationship with WAFs exposure concentrations. Therefore, IBR was suggested to be a potentially useful tool in assessing the oil pollution.

  14. Search for Chemical Biomarkers on Mars Using the Sample Analysis at Mars Instrument Suite on the Mars Science Laboratory (United States)

    Glavin, D. P.; Conrad, P.; Dworkin, J. P.; Eigenbrode, J.; Mahaffy, P. R.


    One key goal for the future exploration of Mars is the search for chemical biomarkers including complex organic compounds important in life on Earth. The Sample Analysis at Mars (SAM) instrument suite on the Mars Science Laboratory (MSL) will provide the most sensitive measurements of the organic composition of rocks and regolith samples ever carried out in situ on Mars. SAM consists of a gas chromatograph (GC), quadrupole mass spectrometer (QMS), and tunable laser spectrometer to measure volatiles in the atmosphere and released from rock powders heated up to 1000 C. The measurement of organics in solid samples will be accomplished by three experiments: (1) pyrolysis QMS to identify alkane fragments and simple aromatic compounds; pyrolysis GCMS to separate and identify complex mixtures of larger hydrocarbons; and (3) chemical derivatization and GCMS extract less volatile compounds including amino and carboxylic acids that are not detectable by the other two experiments.

  15. Multiparameter analysis of biomarkers in the laboratory diagnosis of early rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Aleksandr Aleksandrovich Novikov


    Full Text Available Subjects and methods. 102 patients with early RA (79 women and 23 men; median age 51 years [41 to 62, 25th to 75th percentile]; disease duration 4 months [2.5 to 6.0]; DAS28 5.4 [4.1 to 5.9] were examined. A comparison group consisted of 616 patients including 27 with systemic lupus erythematosus, 15 with Sjö gren’s syndrome, 25 with ankylosing spondyloarthritis; 33 with osteoarthritis, 20 with overlap syndrome, 9, 22, and 168 patients with gouty, psoriatic, and undifferentiated arthritis, respectively; as well as 297 healthy donors matched with the examinees for gender and age. The concentrations of 36 biomarkers were measured by an immunonephelometric method, enzyme immunoassay, and xMAP technology. The values of one variable from others were predicted using a multiple linear regression method (multivariate analysis. Results. The strongest predictors of early RA, such as the concentrations of interleukin-6, C-reactive protein, granulo-cyte-macrophage colony-stimulating factor, interferon-γ (IFN-γ, IFN^-inducible protein, anti-cyclic citrullinated peptide antibodies, were identified and a candidate for MDI was developed for early RA (MIRRA. After thorough validation, MIRRA may be regarded as a precision serological assay for the early diagnosis of RA. Conclusion. The development of MDI having a higher diagnostic precision than routinely used biomarkers is imperative for early RA diagnosis that allows one to initiate active antirheumatic therapy that is able to effectively delay progressive joint injury.

  16. Situating Teachers' Developmental Engineering Experiences in an Inquiry-Based, Laboratory Learning Environment (United States)

    Hardré, Patricia L.; Ling, Chen; Shehab, Randa L.; Nanny, Mark A.; Nollert, Matthias U.; Refai, Hazem; Ramseyer, Christopher; Herron, Jason; Wollega, Ebisa D.; Huang, Su-Min


    Many secondary math and science teachers don't understand the nature and application of engineering adequately to transfer that understanding to their students. Research is needed that investigates and illuminates the process and characteristics of development that addresses this gap. This mixed-method study examines the developmental experiences…

  17. Laboratory evaluation of the efficacy of fluorescent biomarkers for sugar-feeding sand flies (Diptera: Psychodidae). (United States)

    Mascari, T M; Foil, L D


    The purpose of this study was to evaluate the use of four fluorescent dyes (rhodamine B, uranine O, auramine O, and erythrosin B) and two nonfluorescent dyes (carmoisine and indigotine) incorporated into sugar baits as biomarkers for phlebotomine sand flies. Each dye could be detected in sand flies fed baits with dye for 24 h when examined using bright field microscopy, although there was considerable variability in the marking produced; all sand flies that had ingested rhodamine B-treated sucrose solution were marked clearly. Sand flies that had ingested sucrose solution containing rhodamine B or uranine O at concentrations as low as 10 mg/L were consistently detected under fluorescence microscopy. None of the treatments in this study reduced the longevity of sand flies. All sand flies fed sucrose solution containing rhodamine B or uranine O were marked for at least 14 d, whereas only 20% of sand flies were marked 3 d after feeding on a carmoisine-treated solution. When rhodamine B and uranine O were combined in a single sucrose solution or when the dyes were fed sequentially to sand flies, both dyes could be detected in sand flies using fluorescence microscopy. We propose that rhodamine B- or uranine O-treated sucrose baits could be used in ecological studies or to identify portions of the adult sand fly population that could be targeted with insecticide-treated sugar baits.

  18. Developmental origins of metabolic disorders: The need for biomarker candidates and therapeutic targets from adequate preclinical models

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    Antonio Gonzalez-Bulnes


    Full Text Available The investigation on obesity and associated disorders have changed from an scenario in which genome drove the phenotype to a dynamic setup in which prenatal and early-postnatal conditions are determinant. However, research in human beings is difficult due to confounding factors (lifestyle and socioeconomic heterogeneity plus ethical issues. Hence, there is currently an intensive effort for developing adequate preclinical models, aiming for an adequate combination of basic studies in rodent models and specific preclinical studies in large animals. The results of these research strategies may increase the identification and development of contrasted biomarkers and therapeutic targets.

  19. Zebrafish development and genetics: introducing undergraduates to developmental biology and genetics in a large introductory laboratory class. (United States)

    D'Costa, Allison; Shepherd, Iain T


    We have taken advantage of the strengths of the zebrafish model system to introduce developmental biology and genetics to undergraduates in their second semester of the Introductory Biology course at Emory. We designed a 6-week laboratory module based on research being undertaken by faculty in the department, and incorporated experiments that used current research methods including bioinformatics. Students undertook a range of experiments including direct observation of live wild-type zebrafish at different stages of embryogenesis, whole-mount in situ hybridization of mutant and wild-type embryos, vital dye staining of mutant and wild-type embryos, and pharmacological treatments to perturb normal development. These laboratories engaged the students by providing a hands-on, research-centered experience, while also enhancing their written (worksheets and laboratory reports) and oral (group presentation) communication skills. We describe the proceedings of each lab and the logistics of preparing and running these labs for 400-500 students (120 students taking lab each day), and provide a preliminary assessment of the success of the laboratories data based on student evaluations.

  20. Fluctuating asymmetry and developmental instability in Protoreaster nodosus (Chocolate Chip Sea Star as a biomarker for environmental stress

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    D. J. V. Trono


    Full Text Available Fluctuating asymmetry (FA, pertains to small and random departures from perfect symmetry of an organism's bilateral traits and has been used as a measurement of developmental instability and as a potential indicator of stress in populations. It measures the variations from symmetry of a symmetrical structure whose sides are said to be genetically identical, with similar history of gene activity and experiencing the same environment. Symmetries are potentially the basis for studies on FA. Hence, this study assessed the potential of FA as a reliable developmental instability and environmental stress indicator in five-fold dihedral symmetrical Protoreaster nodosus (Chocolate chip sea fish from three (3 different sites (Linamon, Lanao del Norte; Initao, Misamis Oriental and Jasaan, Misamis Oriental. FA for each population from every site was measured for comparison. In this study, anatomical landmarks were subjected to Procrustes superimposition and Principal Component Analysis (PCA using "Symmetry and Asymmetry in Geometric Data" (SAGE program. Results showed highly significant FA and significant DA for population from Jasaan and Linamon where habitat disturbance due to anthropogenic activities were prevalent. Thus, experienced more stress compared to the other populations, suggesting that significant variation in size or left-right side of each individual could be a product of genotype-environment interaction. Moreover, insignificant FA and high DA was obtained from Initao (protected seascape area which indicated that variation among individual genotypes and asymmetry in phenotypes is mostly induced by genetics under less stressful environment. Significant FA and increase FA present inability of species to buffer stress in its developmental pathways and have implications on species fitness. Hypothesis assumes that fluctuating asymmetry has costs, reflects the quality of individuals and the level of genetic and environmental stress experienced by

  1. Vitellogenin as a biomarker for estrogenic effects in brown trout, Salmo trutta: laboratory and field investigations. (United States)

    Bjerregaard, Poul; Hansen, Pernille R; Larsen, Katrine J; Erratico, Claudio; Korsgaard, Bodil; Holbech, Henrik


    The sensitivity of juvenile brown trout towards estrogenic chemicals (17beta-estradiol [E2], estrone [E1], 17alpha-ethinylestradiol [EE2], 4-tert-octylphenol [OP], and n-butylparaben [BP]) was tested in laboratory experiments with plasma and liver vitellogenin concentrations as endpoints. Vitellogenin concentrations were also assessed in juvenile brown trout collected in streams affected by agricultural runoff and discharges from scattered houses in the open land. In the laboratory, juvenile brown trout were exposed to the chemicals in flow-through tanks for 7 to 12 d and concentration-response relationships for the induction of vitellogenin synthesis were obtained. The actual exposure concentrations were determined by liquid chromatography-mass spectrometry. The median plasma vitellogenin concentration in first year control brown trout reared in recirculated groundwater was 165 ng/ml with 783 ng/ml as the highest value. The median effective concentration (EC50) values for vitellogenin induction (based on plasma concentrations) were 3.7 ng EE2/L, 15 ng E2/L, 88 ng E1/L, 68 microg BP/L, and 7 microg OP/L. Median effective concentrations derived from liver vitellogenin concentrations were similar. The 166 brown trout caught in the field were mainly first and second year fish and a few third year fish. Plasma vitellogenin concentrations were below 1000 ng/L in 146 of the fish, between 1000 ng/L and 4234 ng/L in 19 fish and 5.3 x 10(6) ng/L in one male fish. Vitellogenin concentrations did not differ between first and second year fish, but were elevated in third year fish. The data may indicate that juvenile (<2 years) trout with plasma vitellogenin concentrations above 1000 ng/ml have had their vitellogenin synthesis induced by exposure to estrogens in the environment. Plasma and liver vitellogenin concentrations were closely correlated in brown trout with elevated vitellogenin concentrations. It is noteworthy, however, that exposure to synthetic estrogens (EE2, BP

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

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    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

  3. New sepsis biomarkers

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    Dolores Limongi


    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.

  4. New sepsis biomarkers

    Institute of Scientific and Technical Information of China (English)

    Dolores Limongi; Cartesio D’Agostini; Marco Ciotti


    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.

  5. New sepsis biomarkers

    Institute of Scientific and Technical Information of China (English)

    Dolores Limongi; Cartesio DAgostini; Marco Ciotti


    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.

  6. An inter-laboratory investigation of the Arctic sea ice biomarker proxy IP25 in marine sediments: key outcomes and recommendations

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    S. T. Belt


    Full Text Available We describe the results of an inter-laboratory investigation into the identification and quantification of the Arctic sea ice biomarker proxy IP25 in marine sediments. 7 laboratories took part in the study, which consisted of the analysis of IP25 in a series of sediment samples from different regions of the Arctic, sub-Arctic and Antarctic, additional sediment extracts and purified standards. The results obtained allowed 4 key outcomes to be determined. First, IP25 was identified by all laboratories in sediments from the Canadian Arctic with inter-laboratory variation in IP25 concentration being substantially larger than within individual laboratories. This greater variation between laboratories was attributed to the difficulty in accurately determining instrumental response factors for IP25, despite provision of appropriate standards. Second, the identification of IP25 by 3 laboratories in sediment from SW Iceland that was believed to represent a blank, was interpreted as representing a better limit of detection or quantification for such laboratories, contamination or mis-identification. These alternatives could not be distinguished conclusively with the data available, although it is noted that the precision of these data was significantly poorer compared with the other IP25 concentration measurements. Third, 3 laboratories reported the occurrence of IP25 in a sediment sample from the Antarctic Peninsula even though this biomarker is believed to be absent from the Southern Ocean. This anomaly is attributed to a combined chromatographic and mass spectrometric interference that results from the presence of a di-unsaturated highly branched isoprenoid (HBI pseudo-homologue of IP25 that occurs in Antarctic sediments. Finally, data are presented that suggest that extraction of IP25 is consistent between Automated Solvent Extraction (ASE and sonication methods and that IP25 concentrations based on 7-hexylnonadecane as an internal standard are

  7. Target organs of the Manila clam Ruditapes philippinarum for studying metal accumulation and biomarkers in pollution monitoring: laboratory and in-situ transplantation experiments. (United States)

    Won, Eun-Ji; Kim, Kyung-Tae; Choi, Jin-Young; Kim, Eun-Soo; Ra, Kongtae


    To characterize the target organs of the Manila clam Ruditapes philippinarum for use in environmental study, the accumulation of trace metals and three biomarkers was measured in different organs. Exposure with Cu and Pb carried out under laboratory conditions revealed a linear uptake of metals throughout the experimental period in each tissue. In particular, significant increase was observed in gills and mantle. The increase of intracellular reactive oxygen species showed the great potential of gills as a target tissue for both Cu and Pb exposure. The highest activity of glutathione S-transferase and their relative increase in activity were also observed in gills. Metallothionein-like protein levels, however, increased greatly in the digestive gland and mantle during Cu and Pb exposure, respectively, although all tissues, except the foot, showed significant changes after 24 h of metal exposure. In the field study, the highest concentration of metals was recorded in the gills and mantle, accounting for over 50 % of the total accumulated metal in all sites. Additionally, Cu and Pb increased significantly in these two organs, respectively. However, the order of accumulation rate in laboratory exposure was not concomitant with those of the lab-based study, suggesting that different routes of metal uptake and exposure duration induce distinct partitioning of metals and regulating system in R. philippinarum. These series of exposure studies demonstrated that gills, mantle, and digestive gland in R. philippinarum are potential target tissues in environmental monitoring study using metal concentrations and biomarkers.

  8. Role of laboratory biomarkers in monitoring and prediction of the effectiveness of treatment of rheumatic diseases using genetically engineered drugs

    Directory of Open Access Journals (Sweden)

    Elena Nikolayevna Aleksandrova


    Full Text Available Significant progress in treating immunoinflammatory rheumatic diseases (RD is related to the design of a novel family of drugs, genetically engineered (GE drugs. Molecular and cellular biomarkers (antibodies, indicators of acute inflammation, cytokines, chemokines, growth factors, endothelial activation markers, immunoglobulins, cryoglobulins, T- and B-cell subpopulations, products of bone and cartilage metabolism, genetic and metabolic markers that allow one to conduct immunological monitoring and prediction of the effectiveness of RD therapy using tumor necrosis factor α inhibitors (infliximab, adalimumab, golimumab, etanercept, anti-B-cell drugs (rituximab, belimumab, interleukin-6 receptor antagonist (tocilizumab, and T-cell costimulation blocker (abatacept have been detected in blood, synovial fluid, urine, and bioptates of the affected tissues. In addition to the conventional uniplex immunodiagnostics techniques, multiplex analysis of marker, which is based on genetic, transcriptomic and proteomic technologies using DNA and protein microarrays, polymerase chain reaction, and flow cytometry, is becoming increasingly widespread. The search for and validation of immunological predictors of the effective response to GE drug therapy make it possible to optimize and reduce the cost of therapy using these drugs in future.

  9. Role of laboratory biomarkers in monitoring and prediction of the effectiveness of treatment of rheumatic diseases using genetically engineered drugs

    Directory of Open Access Journals (Sweden)

    Elena Nikolayevna Aleksandrova


    Full Text Available Significant progress in treating immunoinflammatory rheumatic diseases (RD is related to the design of a novel family of drugs, genetically engineered (GE drugs. Molecular and cellular biomarkers (antibodies, indicators of acute inflammation, cytokines, chemokines, growth factors, endothelial activation markers, immunoglobulins, cryoglobulins, T- and B-cell subpopulations, products of bone and cartilage metabolism, genetic and metabolic markers that allow one to conduct immunological monitoring and prediction of the effectiveness of RD therapy using tumor necrosis factor α inhibitors (infliximab, adalimumab, golimumab, etanercept, anti-B-cell drugs (rituximab, belimumab, interleukin-6 receptor antagonist (tocilizumab, and T-cell costimulation blocker (abatacept have been detected in blood, synovial fluid, urine, and bioptates of the affected tissues. In addition to the conventional uniplex immunodiagnostics techniques, multiplex analysis of marker, which is based on genetic, transcriptomic and proteomic technologies using DNA and protein microarrays, polymerase chain reaction, and flow cytometry, is becoming increasingly widespread. The search for and validation of immunological predictors of the effective response to GE drug therapy make it possible to optimize and reduce the cost of therapy using these drugs in future.

  10. Biomarkers of intermediate endpoints in environmental and occupational health

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E; Hansen, Ase M


    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...

  11. Prevalence of Candidatus Erwinia dacicola in wild and laboratory olive fruit fly populations and across developmental stages. (United States)

    Estes, Anne M; Hearn, David J; Burrack, Hannah J; Rempoulakis, Polychronis; Pierson, Elizabeth A


    The microbiome of the olive fruit fly, Bactrocera oleae (Gmelin), a worldwide pest of olives (Olea europaea L.), has been examined for >100 yr as part of efforts to identify bacteria that are plant pathogens vectored by the fly or are beneficial endosymbionts essential for the fly's survival and thus targets for possible biological control. Because tephritid fruit flies feed on free-living bacteria in their environment, distinguishing between the transient, acquired bacteria of their diet and persistent, resident bacteria that are vertically transmitted endosymbionts is difficult. Several culture-dependent and -independent studies have identified a diversity of species in the olive fruit fly microbiome, but they have not distinguished the roles of the microbes. Candidatus Erwinia dacicola, has been proposed to be a coevolved endosymbiont of the olive fruit fly; however, this was based on limited samples from two Italian populations. Our study shows that C. Erwinia dacicola was present in all New and Old World populations and in the majority of individuals of all life stages sampled in 2 yr. Olive fruit flies reared on olives in the laboratory had frequencies of C. Erwinia dacicola similar to that of wild populations; however, flies reared on artificial diets containing antibiotics in the laboratory rarely had the endosymbiont. The relative abundance of C. Erwinia dacicola varied across development stages, being most abundant in ovipositing females and larvae. This uniform presence of C. Erwini dacicola suggests that it is a persistent, resident endosymbiont of the olive fruit fly.

  12. Effect of host plants on developmental time and life table parameters of Carposina sasakii (Lepidoptera: Carposinidae) under laboratory conditions. (United States)

    Lei, Xihong; Li, Dingxu; Li, Zheng; Zalom, Frank G; Gao, Lingwang; Shen, Zuorui


    Studies were designed to examine the effects of host plants (apricot, Prunus armeniaca L.; plum, Prunus salicina L.; peach, Prunus persica L.; jujube, Zizyphus jujuba Will.; apple, Malus domestica Mill.; and pear, Pyrus sorotina Will) on the development and life table parameters of the peach fruit moth, Carposina sasakii Matsumura (Lepidoptera: Carposinidae) under laboratory conditions. Peach fruit moth developed faster (12.48 d) and had the highest preimaginal survival rate (50.54%) on plum compared with the other host plants. Adult longevity was significantly longer on jujube for both female and male moths. Adult females from larvae reared on jujube and peach laid significantly greater numbers of eggs (214.50 and 197.94 eggs per female, respectively) compared with those reared on the other four host plants. Life-table parameters were calculated for each host plant and compared by jackknife procedures. The intrinsic rate of natural increase (r(m)) was significantly greatest on plum (0.1294 eggs per female per d), followed by jujube and apricot (0.1201 and 0.1128 eggs per female per d), respectively. Implications of the various measures of population performance are discussed.

  13. Improving tuberculosis diagnostics with biomarkers

    Directory of Open Access Journals (Sweden)

    Shu CC


    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 

  14. 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. (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


    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.

  15. Reproductive biomarkers responses induced by xenoestrogens in the characid fish Astyanax fasciatus inhabiting a South American reservoir: An integrated field and laboratory approach

    Energy Technology Data Exchange (ETDEWEB)

    Prado, Paula S.; Pinheiro, Ana Paula B. [Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, C.P. 486, 30161-970, Minas Gerais (Brazil); Bazzoli, Nilo [Programa de Pós-Graduação em Zoologia de Vertebrados, Pontifícia Universidade Católica de Minas Gerais, PUC Minas, Belo Horizonte 30535-610, Minas Gerais (Brazil); Rizzo, Elizete, E-mail: [Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, C.P. 486, 30161-970, Minas Gerais (Brazil)


    Field studies evaluating the effects of endocrine disruption chemicals (EDCs) on the fish reproduction are scarce worldwide. The goal of this study was to assess hepatic levels of vitellogenin (Vtg), zona radiata proteins (Zrp) and insulin-like growth factors (IGF-I and IGF-II), and relating them to reproductive endpoints in a wild fish population habiting a reservoir that receive domestic sewage, agricultural and industrial residues. Adult fish Astyanax fasciatus were sampled during the reproductive season in five sites from the Furnas Reservoir, Grande River, and Paraguay–Paraná basin. As a control to field data, fish were experimentally exposed via dietary intake, to oestradiol benzoate (OB) for 7 days. Fish from site with little anthropogenic interference showed hepatic levels of Vtg, Zrp and IGF-I and IGF-II similar to those from the non-treated experimental group. In sites located immediately downstream from the municipal wastewater discharges, the water total oestrogen was >120 ng/l, and male fish displayed increased Vtg and Zrp and decreased IGF-I levels similar to OB treated fish. In females, levels of Vtg, Zrp, IGF-I and IGF-II suggest an impairment of final oocyte maturation and spawning, as also detected by frequency of over-ripening, follicular atresia and fecundity. At the sites that receive agricultural and industrial residues, the water total oestrogen was <50 ng/l and females showed decreased Zrp and increased IGF-II levels associated to reduced diameter of vitellogenic follicles, indicating an inhibition of oocyte growth. Overall, the current study reports oestrogenic contamination impairing the reproduction of a wild fish from a hydroeletric reservoir and, the data contribute to improving the current knowledge on relationship between hepatic Vtg, Zrp and IGF-I and IGF-II, and reproductive endpoints in a teleost fish. In addition, our data point out novel reproductive biomarkers (IGF-I, IGF-II and over-ripening) to assessing xenoestrogenic

  16. Imaging Biomarkers or Biomarker Imaging?

    Directory of Open Access Journals (Sweden)

    Markus Mitterhauser


    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. Biomarkers in Barrett's esophagus. (United States)

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


    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

  18. Developmental Evaluation. (United States)

    Patton, Michael Quinn


    Developmental evaluation is proposed as a term to describe certain long-term partnering relationships with clients who are, themselves, engaged in ongoing program development. Rather than a model, developmental evaluation is a relationship founded on a shared purpose and is a way of being useful in innovative settings. (SLD)

  19. Establishing cytogenetic biodosimetry laboratory in Saudi Arabia and producing preliminary calibration curve of dicentric chromosomes as biomarker for medical dose estimation in response to radiation emergencies. (United States)

    Al-Hadyan, Khaled; Elewisy, Sara; Moftah, Belal; Shoukri, Mohamed; Alzahrany, Awad; Alsbeih, Ghazi


    In cases of public or occupational radiation overexposure and eventual radiological accidents, it is important to provide dose assessment, medical triage, diagnoses and treatment to victims. Cytogenetic bio-dosimetry based on scoring of dicentric chromosomal aberrations assay (DCA) is the "gold standard" biotechnology technique for estimating medically relevant radiation doses. Under the auspices of the National Science, Technology and Innovation Plan in Saudi Arabia, we have set up a biodosimetry laboratory and produced a national standard dose-response calibration curve for DCA, pre-required to estimate the doses received. For this, the basic cytogenetic DCA technique needed to be established. Peripheral blood lymphocytes were collected from four healthy volunteers and irradiated with radiation doses between 0 and 5 Gy of 320 keV X-rays. Then, lymphocytes were PHA stimulated, Colcemid division arrested and stained cytogenetic slides were prepared. The Metafer4 system (MetaSystem) was used for automatic and manually assisted metaphase finding and scoring of dicentric chromosomes. Results were fit to the linear-quadratic dose-effect model according to the IAEA EPR-Biodosimetry-2011 report. The resulting manually assisted dose-response calibration curve (Y = 0.0017 + 0.026 × D + 0.081 × D(2)) was in the range of those described in other populations. Although the automated scoring over-and-under estimates DCA at low (2 Gy) doses, respectively, it showed potential for use in triage mode to segregate between victims with potential risk to develop acute radiotoxicity syndromes. In conclusion, we have successfully established the first biodosimetry laboratory in the region and have produced a preliminary national dose-response calibration curve. The laboratory can now contribute to the national preparedness plan in response to eventual radiation emergencies in addition to providing information for decision makers and public health officials who assess the

  20. Delivery of High-Quality Biomarker Assays

    Directory of Open Access Journals (Sweden)

    Brian N. Swanson


    Full Text Available Biomarker measurements now support key decisions throughout the drug development process, from lead optimization to regulatory approvals. They are essential for documenting exposure-response relationships, specificity and potency toward the molecular target, untoward effects, and therapeutic applications. In a broader sense, biomarkers constitute the basis of clinical pathology and laboratory medicine. The utility of biomarkers is limited by their specificity and sensitivity toward the drug or disease process and by their overall variability. Understanding and controlling sources of variability is not only imperative for delivering high-quality assay results, but ultimately for controlling the size and expense of research studies. Variability in biomarker measurements is affected by: biological and environmental factors (e.g., gender, age, posture, diet and biorhythms, sample collection factors (e.g., preservatives, transport and storage conditions, and collection technique, and analytical factors (e.g., purity of reference material, pipetting precision, and antibody specificity. The quality standards for biomarker assays used in support of nonclinical safety studies fall under GLP (FDA regulations, whereas, those assays used to support human diagnostics and healthcare are established by CLIA (CMS regulations and accrediting organizations such as the College of American Pathologists. While most research applications of biomarkers are not regulated, biomarker laboratories in all settings are adopting similar laboratory practices in order to deliver high-quality data. Because of the escalation in demand for biomarker measurements, the highly-parallel (multi-plexed assay platforms that have fueled the rise of genomics will likely evolve into the analytical engines that drive the biomarker laboratories of tomorrow.

  1. Biomarkers of oxidative stress in antioxidant therapy

    Directory of Open Access Journals (Sweden)

    Wilfredo Mañon Rossi


    Full Text Available Biomarkers are used regularly in medical practice to provide objective markers of health status of a person, as well as the physiological response of the body to a pharmacological therapeutic intervention. In the specific case of the use of antioxidant products (antioxidant therapy, it is necessary to measure both biomarkers of oxidative stress level of the person as those that are specific to a physiological or pathological progression of a disease disorder. This paper describes the main biomarkers of oxidative general and specific stress as well as laboratory techniques, which should be taken into account when measuring the effectiveness of antioxidant therapies.

  2. Ready for Prime Time? Biomarkers in Sepsis. (United States)

    Long, Brit; Koyfman, Alex


    Sepsis is a common condition managed in the emergency department. Current diagnosis relies on physiologic criteria and suspicion of a source of infection using history, physical examination, laboratory studies, and imaging studies. The infection triggers a host response with the aim to destroy the pathogen, and this response can be measured. A reliable biomarker for sepsis should assist with earlier diagnosis, improve risk stratification, or improve clinical decision making. Current biomarkers for sepsis include lactate, troponin, and procalcitonin. This article discusses the use of lactate, procalcitonin, troponin, and novel biomarkers for use in sepsis.

  3. Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge; Kristensen, Tage Søndergaard;


    Human Deveoplment and Working Life - Work for Welfare explores whether the development of human resources at company level can improve individuals' quality of life, companies' possibilities of development, and welfare and democracy in society. Chapter two discuss the concept "developmental work...

  4. Biomarkers of teratogenesis: suggestions from animal studies. (United States)

    Giavini, Erminio; Menegola, Elena


    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.

  5. Pre-analytic variability in cardiovascular biomarker testing. (United States)

    Cemin, Roberto; Daves, Massimo


    The impact of laboratory medicine on clinical cardiology has dramatically increased over the years and a lot of cardiovascular biomarkers have been recently proposed. In order to avoid clinical mistakes, physicians should be well aware of all the aspects, which could affect the quality of laboratory results, remembering that pre-analytic variability is an often overlooked significant source of bias, determining the vast majority of laboratory errors. This review addresses the determinants of pre-analitycal variability in cardiovascular biomarker testing, focusing on the most widespread biomarkers, which are cardiac troponins and natriuretic peptides.

  6. Validation of Biomarker-based risk prediction models


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


    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...

  7. Biomarkers in Veterinary Medicine. (United States)

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


    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.

  8. Combination of biomarkers

    DEFF Research Database (Denmark)

    Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger;


    The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

  9. Unraveling the Miswired Connectome: A Developmental Perspective (United States)

    Di Martino, Adriana; Fair, Damien A.; Kelly, Clare; Satterthwaite, Theodore D.; Castellanos, F. Xavier; Thomason, Moriah E.; Craddock, R. Cameron; Luna, Beatriz; Leventhal, Bennett L.; Zuo, Xi-Nian; Milham, Michael P.


    Summary The vast majority of mental illnesses can be conceptualized as developmental disorders of neural interactions within the connectome, or developmental miswiring. The recent maturation of pediatric in vivo brain imaging is bringing within reach the identification of clinically meaningful brain-based biomarkers of developmental disorders. Even more auspicious, is the ability to study the evolving connectome throughout life, beginning in utero, which promises to move the field from topological phenomenology to etiological nosology. Here, we scope advances in pediatric imaging of the brain connectome as the field faces the challenge of unraveling developmental miswiring. We highlight promises while also providing a pragmatic review of the many obstacles ahead that must be overcome to significantly impact public health. PMID:25233316

  10. Cardiorenal biomarkers in acute heart failure

    Institute of Scientific and Technical Information of China (English)

    Rajiv Choudhary; Dipika Gopal; Ben A. Kipper; Alejandro De La Parra Landa; Hermineh Aramin


    Managing patients with heart failure (HF) is a challenging task within itself, but the presence of associated worsening renal function can greatly increase mortality and morbidity. Early diagnosis and treatment is the key to prevent re-hospitalizations and reduce healthcare costs. Biomarkers have long been established as highly sensitive and specific tools in diagnosing and prognosticating patients with HF. Reflecting distinct pathophysiological events and ongoing cellular insult, biomarkers have been proven superior to conventional laboratory tests. Availability of better assays and rapid analysis has allowed the use of biomarkers as point-of-care tests in the emergency department and at the patient's bed-side. Acute HF patients often go on to develop worsening renal function, termed as acute cardiorenal syndrome. The growing breadth of studies has shown the implications of combining multiple biomarkers to better chart outcomes and produce desirable results in such patients.

  11. Renal Cancer Biomarkers | NCI Technology Transfer Center | TTC (United States)

    The National Cancer Institute's Laboratory of Proteomics and Analytical Technologies is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic, therapeutic and prognostic cancer biomarkers from clinical specimens.

  12. "Do I Need to Know This for the Exam?" Using Popular Media, Inquiry-based Laboratories, and a Community of Scientific Practice to Motivate Students to Learn Developmental Biology (United States)

    Madhuri, Marga; Broussard, Christine


    One of the greatest challenges instructors face is getting students to connect with the subject in a manner that encourages them to learn. In this essay, we describe the redesign of our Developmental Biology course to foster a deeper connection between students and the field of developmental biology. In our approach, we created a community of…

  13. Developmental Scaffolding

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio


    The concept of scaffolding has wide resonance in several scientific fields. Here we attempt to adopt it for the study of development. In this perspective, the embryo is conceived as an integral whole, comprised of several hierarchical modules as in a recurrent circularity of emerging patterns....... Within the developmental hierarchy, each module yields an inter-level relationship that makes it possible for the scaffolding to mediate the production of selectable variations. Awide range of genetic, cellular and morphological mechanisms allows the scaffolding to integrate these modular variations...... into a functionally coordinate unit. A genetic scaffolding accounts for the inherited invariance of pattern formation during the embryo’s growth. At higher level, cells behave as agents endowed with the capacity to interpret any scaffolding variation as signs. The full hierarchy of a multi-level scaffolding...

  14. Developmental dyslexia. (United States)

    Peterson, Robin L; Pennington, Bruce F


    This review uses a levels-of-analysis framework to summarize the current understanding of developmental dyslexia's etiology, brain bases, neuropsychology, and social context. Dyslexia is caused by multiple genetic and environmental risk factors as well as their interplay. Several candidate genes have been identified in the past decade. At the brain level, dyslexia is associated with aberrant structure and function, particularly in left hemisphere reading/language networks. The neurocognitive influences on dyslexia are also multifactorial and involve phonological processing deficits as well as weaknesses in other oral language skills and processing speed. We address contextual issues such as how dyslexia manifests across languages and social classes as well as what treatments are best supported. Throughout the review, we highlight exciting new research that cuts across levels of analysis. Such work promises eventually to provide a comprehensive explanation of the disorder as well as its prevention and remediation.

  15. Biomarkers in clinical medicine. (United States)

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


    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.

  16. Biomarkers for Parkinson's disease. (United States)

    Sherer, Todd B


    Biomarkers for detecting the early stages of Parkinson's disease (PD) could accelerate development of new treatments. Such biomarkers could be used to identify individuals at risk for developing PD, to improve early diagnosis, to track disease progression with precision, and to test the efficacy of new treatments. Although some progress has been made, there are many challenges associated with developing biomarkers for detecting PD in its earliest stages.

  17. Urinary iodine, thyroid function, and thyroglobulin as biomarkers of iodine status. (United States)

    Pearce, Elizabeth N; Caldwell, Kathleen L


    The accurate assessment of population iodine status is necessary to inform public health policies and clinical research on iodine nutrition, particularly the role of iodine adequacy in normal neurodevelopment. Urinary iodine concentration (UIC) directly reflects dietary iodine intake and is the most common indicator used worldwide to assess population iodine status. The CDC established the Ensuring the Quality of Iodine Procedures program in 2001 to provide laboratories that measure urinary iodine with an independent assessment of their analytic performance; this program fosters improvement in the assessment of UIC. Clinical laboratory tests of thyroid function (including serum concentrations of the pituitary hormone thyrotropin and the thyroid hormones thyroxine and triiodothyronine) are sometimes used as indicators of iodine status, although such use is often problematic. Even in severely iodine-deficient regions, there is a great deal of intraindividual variation in the ability of the thyroid to adapt. In most settings and in most population subgroups other than newborns, thyroid function tests are not considered sensitive indicators of population iodine status. However, the thyroid-derived protein thyroglobulin is increasingly being used for this purpose. Thyroglobulin can be measured in either serum or dried blood spot (DBS) samples. The use of DBS samples is advantageous in resource-poor regions. Improved methodologies for ascertaining maternal iodine status are needed to facilitate research on developmental correlates of iodine status. Thyroglobulin may prove to be a useful biomarker for both maternal and neonatal iodine status, but validated assay-specific reference ranges are needed for the determination of iodine sufficiency in both pregnant women and neonates, and trimester-specific ranges are possibly needed for pregnant women. UIC is currently a well-validated population biomarker, but individual biomarkers that could be used for research, patient care

  18. Developmental dyspraxia and developmental coordination disorder. (United States)

    Miyahara, M; Möbs, I


    This article discusses the role developmental dyspraxia plays in developmental coordination disorder (DCD), based upon a review of literature on apraxia, developmental dyspraxia, and DCD. Apraxia and dyspraxia have often been equated with DCD. However, it is argued that apraxia and dyspraxia primarily refer to the problems of motor sequencing and selection, which not all children with DCD exhibit. The author proposes to distinguish developmental dyspraxia from DCD. Other issues discussed include the assessment, etiology, and treatment of developmental dyspraxia and DCD, and the relationship between DCD and learning disabilities. A research agenda is offered regarding future directions to overcome current limitation.

  19. Biomarkers in aquatic plants: selection and utility. (United States)

    Brain, Richard A; Cedergreen, Nina


    This review emphasizes the predictive ability, sensitivity and specificity of aquatic plant biomarkers as biomonitoring agents of exposure and effect. Biomarkers of exposure are those that provide functional measures of exposure that are characterized at a sub-organism level. Biomarkers of effect require causal linkages between the biomarker and effects, measured at higher levels of biological organization. With the exception of pathway specific metabolites, the biomarkers assessed in this review show variable sensitivity and predictive ability that is often confounded by variations in growth conditions, rendering them unsuitable as stand alone indicators of environmental stress. The use of gene expression for detecting pollution has been, and remains immature; this immaturity derives from inadequate knowledge on predictive ability, sensitivity and specificity. Moreover, the ability to the detect mode of action of unknown toxicants using gene expression is not as clear-cut as initially hypothesized. The principal patterns in gene expression is not as clear-cut as initially hypothesized. The principal patterns in gene expression are generally derived from stress induced genes, rather than on ones that respond to substances with known modes of action (Baerson et al. 2005). Future developments in multivariate statistics and chemometric methods that enhance pattern analyses in ways that could produce a "fingerprint", may improve methods for discovering modes of action of unknown toxicants. Pathway specific metabolites are unambiguous, sensitive, correlate well to growth effects, and are relatively unaffected by growth conditions. These traits make them excellent biomarkers under both field and laboratory conditions. Changes in metabolites precede visible growth effects; therefore, measuring changes in metabolite concentrations (Harring et al. 1998; Shaner et al. 2005). The metabolic phase I enzymes (primarily associated with P-450 activity) are non-specific biomarkers

  20. Anesthetic-Induced Developmental Neurotoxicity

    Institute of Scientific and Technical Information of China (English)

    Jia-RenLiu; Qian Liu; Jing Li; Sulpicio G. Soriano


    1 IntroductionMillions of newborn and infants receive anesthetic,sedative and analgesic drugs for surgery and painful procedures on a daily basis.Recent laboratory reports clearly demonstrate that anesthetic and sedative drugs induced both neuroapoptosis and neurocognitive deficits in laboratory models.This issue is of paramount interest to pediatric anesthesiologists and intensivists because it questions the safety of anesthetics used for fetal and neonatal anesthesia[1-2].In an attempt to summarize the rapidly expanding laboratorybased literature on anesthetic-induced developmental neurotoxicity (AIDN),this review will examine published reports on the characterization,mechanisms and alleviation of this phenomenon.

  1. Respiratory Toxicity Biomarkers (United States)

    The advancement in high throughput genomic, proteomic and metabolomic techniques have accelerated pace of lung biomarker discovery. A recent growth in the discovery of new lung toxicity/disease biomarkers have led to significant advances in our understanding of pathological proce...

  2. On consensus biomarker selection

    Directory of Open Access Journals (Sweden)

    Gambin Anna


    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.

  3. Biomarkers of Reflux Disease. (United States)

    Kia, Leila; Pandolfino, John E; Kahrilas, Peter J


    Gastroesophageal reflux disease (GERD) encompasses an array of disorders unified by the reflux of gastric contents. Because there are many potential disease manifestations, esophageal and extraesophageal, there is no single biomarker of the entire disease spectrum; a set of GERD biomarkers that each quantifies specific aspects of GERD-related pathology might be needed. We review recent reports of biomarkers of GERD, specifically in relation to endoscopically negative esophageal disease and excluding conventional pH-impedance monitoring. We consider histopathologic biomarkers, baseline impedance, and serologic assays to determine that most markers are based on manifestations of impaired esophageal mucosal integrity, which is based on increased ionic and molecular permeability, and/or destruction of tight junctions. Impaired mucosal integrity quantified by baseline mucosal impedance, proteolytic fragments of junctional proteins, or histopathologic features has emerged as a promising GERD biomarker.

  4. Biomarkers in Parkinson's disease. (United States)

    Morgan, John C; Mehta, Shyamal H; Sethi, Kapil D


    Biomarkers are objectively measured characteristics that are indicators of normal biological processes, pathogenic processes, or responses to therapeutic interventions. To date, clinical assessment remains the gold standard in the diagnosis of Parkinson's disease (PD) and clinical rating scales are well established as the gold standard for tracking progression of PD. Researchers have identified numerous potential biomarkers that may aid in the differential diagnosis of PD and/or tracking disease progression. Clinical, genetic, blood and cerebrospinal fluid (proteomics, transcriptomics, metabolomics), and neuroimaging biomarkers may provide useful tools in the diagnosis of PD and in measuring disease progression and response to therapies. Some potential biomarkers are inexpensive and do not require much technical expertise, whereas others are expensive or require specialized equipment and technical skills. Many potential biomarkers in PD show great promise; however, they need to be assessed for their sensitivity and specificity over time in large and varied samples of patients with and without PD.

  5. The role of metabolic biomarkers in drug toxicity studies. (United States)

    Schnackenberg, Laura K; Beger, Richard D


    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.

  6. Educating for social responsibility: changing the syllabus of developmental biology. (United States)

    Gilbert, Scott F; Fausto-Sterling, Anne


    Developmental biology is deeply embedded in the social issues of our times. Such topics as cloning, stems cells, reproductive technologies, sex selection, environmental hormone mimics and gene therapy all converge on developmental biology. It is therefore critical that developmental biologists learn about the possible social consequences of their work and of the possible molding of their discipline by social forces. We present two models for integrating social issues into the developmental biology curriculum. One model seeks to place discussions of social issues into the laboratory portion of the curriculum; the other model seeks to restructure the course, such that developmental biology and its social contexts are synthesized directly.

  7. [Biomarkers in Alzheimer's disease]. (United States)

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


    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.

  8. Metabolic products as biomarkers (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.


    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.

  9. Commentary: statistics for biomarkers. (United States)

    Lovell, David P


    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.

  10. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

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


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

  11. Biomarker time out. (United States)

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


    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.

  12. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung


    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  13. Biomarkers for neuromyelitis optica. (United States)

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


    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.

  14. Methodological and analytic considerations for blood biomarkers. (United States)

    Christenson, Robert H; Duh, Show-Hong


    Biomarkers typically evolve from a research setting to use in clinical care as evidence for their independent contribution to patient management accumulates. This evidence relies heavily on knowledge of the preanalytical, analytical, and postanalytical characteristics of the biomarker's measurement. For the preanalytical phase, considerations such specimen type, acceptable anticoagulants for blood samples, biologic variation and stability of the biomarker under various conditions are key. The analytical phase entails critical details for development and maintenance of assays having performance characteristics that are "fit for service" for the clinical application at hand. Often, these characteristics describe the ability to measure minute quantities in the biologic matrix used for measurement. Although techniques such as mass spectrometry are used effectively for biomarker discovery, routine quantification often relies on use of immunoassays; early in development, the most common immunoassay used is the enzyme-linked immunosorbent assay format. As biomarkers evolve successfully, they will be adapted to large main laboratory platforms or, depending on the need for speed, point-of-care devices. Users must pay particular attention to performance parameters of assays they are considering for clinical implementation. These parameters include the limit of blank, a term used to describe the limit of analytical noise for an assay; limit of detection, which describes the lowest concentration that can reliably be discriminated from analytical noise; and perhaps most importantly, the limit of quantitation, which is the lowest concentration at which a biomarker can be reliably measured within some predefined specifications for total analytical error that is based on clinical requirements of the test. The postanalytical phase involves reporting biomarker values, which includes reporting units, any normalization factors, and interpretation. Standardization, a process that

  15. Identifying module biomarkers from gastric cancer by differential correlation network

    Directory of Open Access Journals (Sweden)

    Liu X


    Full Text Available Xiaoping Liu,1–3,* Xiao Chang1,3,* 1College of Statistics and Applied Mathematics, Anhui University of Finance and Economics, Bengbu, Anhui Province, People’s Republic of China; 2Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 3Collaborative Research Center for Innovative Mathematical Modeling, Institute of Industrial Science, University of Tokyo, Tokyo, Japan *These authors contributed equally to this work Abstract: Gastric cancer (stomach cancer is a severe disease caused by dysregulation of many functionally correlated genes or pathways instead of the mutation of individual genes. Systematic identification of gastric cancer biomarkers can provide insights into the mechanisms underlying this deadly disease and help in the development of new drugs. In this paper, we present a novel network-based approach to predict module biomarkers of gastric cancer that can effectively distinguish the disease from normal samples. Specifically, by assuming that gastric cancer has mainly resulted from dysfunction of biomolecular networks rather than individual genes in an organism, the genes in the module biomarkers are potentially related to gastric cancer. Finally, we identified a module biomarker with 27 genes, and by comparing the module biomarker with known gastric cancer biomarkers, we found that our module biomarker exhibited a greater ability to diagnose the samples with gastric cancer. Keywords: biomarkers, gastric cancer, stomach cancer, differential network

  16. The Domain of Developmental Psychopathology. (United States)

    Sroufe, L. Alan; Rutter, Michael


    Describes how developmental psychopathology differs from related disciplines, including abnormal psychology, psychiatry, clinical child psychology, and developmental psychology. Points out propositions underlying a developmental perspective and discusses implications for research in developmental psychopathology. (Author/RH)

  17. Developmental Triclosan Exposure Decreases Maternal and Offspring Thyroxine in Rats* (United States)

    Epidemiological and laboratory data have demonstrated that disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring. In a short-term exposure paradigm, triclosan decreased systemic thyroxine (T4) concentr...

  18. Developmental origin of immune diseases - Environmental influences

    DEFF Research Database (Denmark)

    Strom, M.; Halldorsson, T. I.; Hansen, S.


    (PCBs), organochlorine pesticides, andmorerecently perfluoroalkyl substances (PFAS). Developmental exposures to PCBs have, for example, been associated with both otitis media and lower respiratory infections. Evidence regarding asthma and allergic disease is less well established, partly due to lack...... years of age we have examined the long term consequences of in utero exposure to POPs on offspring use of asthma medication and biomarkers of allergic airway disease. Using registry based information on offspring use of asthma medication until 20 years of age, prenatal exposures to PCB-118...... in relation to other registry based information on immune disease is currently in preparation....

  19. What is developmental dyspraxia? (United States)

    Dewey, D


    The idea of developmental dyspraxia has been discussed in the research literature for almost 100 years. However, there continues to be a lack of consensus regarding both the definition and description of this disorder. This paper presents a neuropsychologically based operational definition of developmental dyspraxia that emphasizes that developmental dyspraxia is a disorder of gesture. Research that has investigated the development of praxis is discussed. Further, different types of gestural disorders displayed by children and different mechanisms that underlie developmental dyspraxia are compared to and contrasted with adult acquired apraxia. The impact of perceptual-motor, language, and cognitive impairments on children's gestural development and the possible associations between these developmental disorders and developmental dyspraxia are also examined. Also, the relationship among limb, orofacial, and verbal dyspraxia is discussed. Finally, problems that exist in the neuropsychological assessment of developmental dyspraxia are discussed and recommendations concerning what should be included in such an assessment are presented.


    Federal Laboratory Consortium — Naval Academy Hydromechanics Laboratory The Naval Academy Hydromechanics Laboratory (NAHL) began operations in Rickover Hall in September 1976. The primary purpose...

  1. Bioassay Laboratory (United States)

    Federal Laboratory Consortium — The Bioassay Laboratory is an accredited laboratory capable of conducting standardized and innovative environmental testing in the area of aquatic ecotoxicology. The...


    Federal Laboratory Consortium — Naval Academy Hydromechanics LaboratoryThe Naval Academy Hydromechanics Laboratory (NAHL) began operations in Rickover Hall in September 1976. The primary purpose of...

  3. Biomarkers intersect with the exposome. (United States)

    Rappaport, Stephen M


    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.

  4. Doing Developmental Research: A Practical Guide (United States)

    Striano, Tricia


    Addressing practical issues rarely covered in methods texts, this user-friendly, jargon-free book helps students and beginning researchers plan infant and child development studies and get them done. The author provides step-by-step guidance for getting involved in a developmental laboratory and crafting effective research questions and proposals.…

  5. Carbohydrate biomarkers for future disease detection and treatment

    Institute of Scientific and Technical Information of China (English)

    REID; Suazette


    Carbohydrates are considered as one of the most important classes of biomarkers for cell types,disease states,protein functions,and developmental states.Carbohydrate"binders"that can specifically recognize a carbohydrate biomarker can be used for developing novel types of site specific delivery methods and imaging agents.In this review,we present selected examples of important carbohydrate biomarkers and how they can be targeted for the development of therapeutic and diagnostic agents.Examples are arranged based on disease categories including(1) infectious diseases,(2) cancer,(3) inflammation and immune responses,(4) signal transduction,(5) stem cell transformation,(6) embryo development,and(7) cardiovascular diseases,though some issues cross therapeutic boundaries.

  6. Biomarkers for systemic lupus erythematosus. (United States)

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


    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.

  7. Emerging Biomarkers in Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Mairéad G.; Sahebjam, Solmaz; Mason, Warren P., E-mail: [Pencer Brain Tumor Centre, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada)


    Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6)-methlyguanine-DNA-methyltransferase (MGMT) promoter and deoxyribonucleic acid (DNA) methylation, loss of heterozygosity (LOH) of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH) mutations, epidermal growth factor receptor (EGFR), epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, phosphatase and tensin homolog (PTEN), p16INK4a gene, cytochrome c oxidase (CcO), phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA]), microRNAs (miRNAs), cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future.

  8. 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


    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...

  9. MicroRNA as potential biomarkers in Glioblastoma. (United States)

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


    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.

  10. Developmental Prosopagnosia: A Review

    Directory of Open Access Journals (Sweden)

    Thomas Kress


    Full Text Available This article reviews the published literature on developmental prosopagnosia, a condition in which the ability to recognize other persons by facial information alone has never been acquired. Due to the very low incidence of this syndrome, case reports are sparse. We review the available data and suggest assessment strategies for patients suffering from developmental prosopagnosia. It is suggested that developmental prosopagnosia is not a unitary condition but rather consists of different subforms that can be dissociated on the grounds of functional impairments. On the basis of the available evidence, hypotheses about the aetiology of developmental prosopagnosia as well as about the selectivity of deficits related to face recognition are discussed.

  11. Neuroimaging Biomarkers for Psychosis (United States)

    Hager, Brandon M.


    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

  12. Colon Cancer Biomarkers To Identify Patients Suitable For Therapeutic Intervention | NCI Technology Transfer Center | TTC (United States)

    The National Cancer Institute's Laboratory of Human Carcinogenesis is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize cancer biomarkers and therapeutic targets.

  13. Mapping ethical and social aspects of cancer biomarkers. (United States)

    Blanchard, Anne


    Cancer biomarkers represent a revolutionary advance toward personalised cancer treatment, promising therapies that are tailored to subgroups of patients sharing similar generic traits. Notwithstanding the optimism driving this development, biomarkers also present an array of social and ethical questions, as witnessed in sporadic debates across different literatures. This review article seeks to consolidate these debates in a mapping of the complex terrain of ethical and social aspects of cancer biomarker research. This mapping was undertaken from the vantage point offered by a working cancer biomarker research centre called the Centre for Cancer Biomarkers (CCBIO) in Norway, according to a dialectic move between the literature and discussions with researchers and practitioners in the laboratory. Starting in the lab, we found that, with the exception of some classical bioethical dilemmas, researchers regarded many issues relative to the ethos of the biomarker community; how the complexity and uncertainty characterising biomarker research influence their scientific norms of quality. Such challenges to the ethos of cancer research remain largely implicit, outside the scope of formal bioethical enquiry, yet form the basis for other social and ethical issues. Indeed, looking out from the lab we see how questions of complexity, uncertainty and quality contribute to debates around social and global justice; undermining policies for the prioritisation of care, framing the stratification of those patients worthy of treatment, and limiting global access to this highly sophisticated research. We go on to discuss biomarker research within the culturally-constructed 'war on cancer' and highlight an important tension between the expectations of 'magic bullets' and the complexity and uncertainty faced in the lab. We conclude by arguing, with researchers in the CCBIO, for greater reflexivity and humility in cancer biomarker research and policy.

  14. Genetics and Developmental Psychology (United States)

    Plomin, Robert


    One of the major changes in developmental psychology during the past 50 years has been the acceptance of the important role of nature (genetics) as well as nurture (environment). Past research consisting of twin and adoption studies has shown that genetic influence is substantial for most domains of developmental psychology. Present research…

  15. Biomarkers of Selenium Status

    Directory of Open Access Journals (Sweden)

    Gerald F. Combs, Jr.


    Full Text Available The essential trace element, selenium (Se, has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic potential; and very high Se intakes can produce adverse effects. This hierarchy of biological activities calls for biomarkers informative at different levels of Se exposure. Some Se-biomarkers, such as the selenoproteins and particularly GPX3 and SEPP1, provide information about function directly and are of value in identifying nutritional Se deficiency and tracking responses of deficient individuals to Se-treatment. They are useful under conditions of Se intake within the range of regulated selenoprotein expression, e.g., for humans <55 μg/day and for animals <20 μg/kg diet. Other Se-biomarkers provide information indirectly through inferences based on Se levels of foods, tissues, urine or feces. They can indicate the likelihood of deficiency or adverse effects, but they do not provide direct evidence of either condition. Their value is in providing information about Se status over a wide range of Se intake, particularly from food forms. There is need for additional Se biomarkers particularly for assessing Se status in non-deficient individuals for whom the prospects of cancer risk reduction and adverse effects risk are the primary health considerations. This would include determining whether supranutritional intakes of Se may be required for maximal selenoprotein expression in immune surveillance cells. It would also include developing methods to determine low molecular weight Se-metabolites, i.e., selenoamino acids and methylated Se-metabolites, which to date have not been detectable in biological specimens. Recent analytical advances using tandem liquid chromatography-mass spectrometry suggest prospects for detecting these metabolites.

  16. Photometrics Laboratory (United States)

    Federal Laboratory Consortium — Purpose:The Photometrics Laboratory provides the capability to measure, analyze and characterize radiometric and photometric properties of light sources and filters,...

  17. Target Laboratory (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  18. Blackroom Laboratory (United States)

    Federal Laboratory Consortium — FUNCTION: Enables evaluation and characterization of materials ranging from the ultraviolet to the longwave infrared (LWIR).DESCRIPTION: The Blackroom Laboratory is...

  19. Blackroom Laboratory (United States)

    Federal Laboratory Consortium — FUNCTION: Enables evaluation and characterization of materials ranging from the ultraviolet to the longwave infrared (LWIR). DESCRIPTION: The Blackroom Laboratory is...

  20. Developmental neurological effects of dioxin-like compounds -- Relative species sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Henshel, D.S. [Indiana Univ., Bloomington, IN (United States). School of Public and Environmental Affairs


    2,3,7,8-Tetrachlorodibenzo-p-dioxin and related compounds are known to be teratogenic. Studies have shown that in ovo exposure to these compounds causes teratogenic changes in the brain which are manifested as a gross bilateral asymmetry in the forebrain and tectum. Through field and laboratory studies the authors are trying to determine whether this endpoint will be generally useful as a biomarker for dioxin-related developmental effects. The ultimate aim is to use this information to establish toxic equivalents for the developmental neurotoxic effects of TCDD and related compounds. In order to properly establish relative toxic equivalents (the focus of this session), one needs to know both the relative effects of different compounds on a single species, at a single life stage, and the relative effects of similar (preferably the same compounds) on different species. Hatchlings or nestlings of several species (great blue heron, doublecrested cormorants, bald eagle) were used in these studies. The brains were measured, and evaluated for bilateral asymmetry. The difference between the two sides of the brain was correlated to the levels of contaminants in either sibling eggs or in plasma from the same bird. These correlations were determined using a variety of published toxic equivalence schemes based on several different endpoints. In a parallel laboratory study, fertile chicken eggs were injected with known concentrations of TCDD from the start of incubation. The clear dose-response relationship between TCDD concentrations and the degree of asymmetry indicates that at least some of the observed gross brain asymmetry is mediated by TCDD-like activity, thus validating the use of TCDD-based toxic equivalents for this particular endpoint.

  1. IDBD: infectious disease biomarker database. (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


    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 and

  2. Examining Autism Spectrum Disorders by Biomarkers: Example from the Oxytocin and Serotonin Systems (United States)

    Hammock, Elizabeth; Veenstra-VanderWeele, Jeremy; Yan, Zhongyu; Kerr, Travis M.; Morris, Marianna; Anderson, George M.; Carter, C. Sue; Cook, Edwin H.; Jacob, Suma


    Objective: Autism spectrum disorder (ASD) is a heritable but highly heterogeneous neuropsychiatric syndrome, which poses challenges for research relying solely on behavioral symptoms or diagnosis. Examining biomarkers may give us ways to identify individuals who demonstrate specific developmental trajectories and etiological factors related to…

  3. The 2D:4D digit ratio as biomarker for substance abuse

    NARCIS (Netherlands)

    Fernstrand, A.M.; Van Den Borne, L.; Lensvelt, L.M.H.; Ribbert, L.L.A.; De With, A.C.; Goede, L.X.Y.; Garssen, J.; Verster, J.C.


    Purpose: The second (2D, index finger) to fourth (4D, ring finger) digit ratio is a biomarker for prenatal testosterone and estrogen exposure. It has been hypothesized that the developmental origins of health and behavior are modulated by the presence or absence of prenatal sex hormones. Several stu

  4. Life Span Developmental Approach

    Directory of Open Access Journals (Sweden)

    Ali Eryilmaz


    Full Text Available The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of individuals with respect to developmental stages. This developmental approach suggests that scientific disciplines should not explain developmental facts only with age changes. Along with aging, cognitive, biological, and socioemotional development throughout life should also be considered to provide a reasonable and acceptable context, guideposts, and reasonable expectations for the person. There are three important subjects whom life span developmental approach deals with. These are nature vs nurture, continuity vs discontinuity, and change vs stability. Researchers using life span developmental approach gather and produce knowledge on these three most important domains of individual development with their unique scientific methodology.

  5. Early diagnosis of complex diseases by molecular biomarkers, network biomarkers, and dynamical network biomarkers. (United States)

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


    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

  6. A versatile microparticle-based immunoaggregation assay for macromolecular biomarker detection and quantification.

    Directory of Open Access Journals (Sweden)

    Haiyan Wu

    Full Text Available The rapid, sensitive and low-cost detection of macromolecular biomarkers is critical in clinical diagnostics, environmental monitoring, research, etc. Conventional assay methods usually require bulky, expensive and designated instruments and relative long assay time. For hospitals and laboratories that lack immediate access to analytical instruments, fast and low-cost assay methods for the detection of macromolecular biomarkers are urgently needed. In this work, we developed a versatile microparticle (MP-based immunoaggregation method for the detection and quantification of macromolecular biomarkers. Antibodies (Abs were firstly conjugated to MP through streptavidin-biotin interaction; the addition of macromolecular biomarkers caused the aggregation of Ab-MPs, which were subsequently detected by an optical microscope or optical particle sizer. The invisible nanometer-scale macromolecular biomarkers caused detectable change of micrometer-scale particle size distributions. Goat anti-rabbit immunoglobulin and human ferritin were used as model biomarkers to demonstrate MP-based immunoaggregation assay in PBS and 10% FBS to mimic real biomarker assay in the complex medium. It was found that both the number ratio and the volume ratio of Ab-MP aggregates caused by biomarker to all particles were directly correlated to the biomarker concentration. In addition, we found that the detection range could be tuned by adjusting the Ab-MP concentration. We envision that this novel MP-based immunoaggregation assay can be combined with multiple detection methods to detect and quantify macromolecular biomarkers at the nanogram per milliliter level.

  7. Biomarker Identification Using Text Mining

    Directory of Open Access Journals (Sweden)

    Hui Li


    Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

  8. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma


    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.

  9. Socialization and Developmental Change. (United States)

    Maccoby, E. E.


    Considers the divergent paths taken by research in cognitive development and research in social-emotional development, arguing that studies of socialization need to become more developmental. Discusses meanings of development that may affect the socialization process. (Author/CI)

  10. Current techniques for assessing developmental neurotoxicity of pesticides

    Institute of Scientific and Technical Information of China (English)

    Yu GAO; Ying TIAN; Xiaoming SHEN


    Organophosphates (OPs) and Pyrethroids (PRY) have been widely used in agriculture and in the home as broad spectrum insecticides, but may produce considerable risk to human health, especially to children. Children are more susceptible to environmental exposure, and concern about the neurotoxic effects of pesticide exposure on children is increasing. There is a need for better understanding of the potential developmental neu-rotoxicity of pesticides. Techniques for assessing devel-opmental neurotoxicity of pesticides will continue to be developed, rendering a need for flexibility of testing para-digms. Current techniques used in evaluating the devel-opmental neurotoxicity of OPs and PRY are presented in this review. These include: (1) In vitro techniques (PC12 cells, C6 cells and other cell models); (2) Non-mammalian models (sea urchins, zebrafish and other non-mammalian models); and (3) In vivo mammalian models (morpho-logical techniques, neurobehavioral assessments and biomarkers).

  11. Chiral Biomarkers in Meteorites (United States)

    Hoover, Richard B.


    The chirality of organic molecules with the asymmetric location of group radicals was discovered in 1848 by Louis Pasteur during his investigations of the rotation of the plane of polarization of light by crystals of sodium ammonium paratartrate. It is well established that the amino acids in proteins are exclusively Levorotary (L-aminos) and the sugars in DNA and RNA are Dextrorotary (D-sugars). This phenomenon of homochirality of biological polymers is a fundamental property of all life known on Earth. Furthermore, abiotic production mechanisms typically yield recemic mixtures (i.e. equal amounts of the two enantiomers). When amino acids were first detected in carbonaceous meteorites, it was concluded that they were racemates. This conclusion was taken as evidence that they were extraterrestrial and produced by abiologically. Subsequent studies by numerous researchers have revealed that many of the amino acids in carbonaceous meteorites exhibit a significant L-excess. The observed chirality is much greater than that produced by any currently known abiotic processes (e.g. Linearly polarized light from neutron stars; Circularly polarized ultraviolet light from faint stars; optically active quartz powders; inclusion polymerization in clay minerals; Vester-Ulbricht hypothesis of parity violations, etc.). This paper compares the measured chirality detected in the amino acids of carbonaceous meteorites with the effect of these diverse abiotic processes. IT is concluded that the levels observed are inconsistent with post-arrival biological contamination or with any of the currently known abiotic production mechanisms. However, they are consistent with ancient biological processes on the meteorite parent body. This paper will consider these chiral biomarkers in view of the detection of possible microfossils found in the Orgueil and Murchison carbonaceous meteorites. Energy dispersive x-ray spectroscopy (EDS) data obtained on these morphological biomarkers will be

  12. Towards Improved Biomarker Research

    DEFF Research Database (Denmark)

    Kjeldahl, Karin

    This thesis takes a look at the data analytical challenges associated with the search for biomarkers in large-scale biological data such as transcriptomics, proteomics and metabolomics data. These studies aim to identify genes, proteins or metabolites which can be associated with e.g. a diet, dis...... is used both for regression and classification purposes. This method has proven its strong worth in the multivariate data analysis throughout an enormous range of applications; a very classic data type is near infrared (NIR) data, but many similar data types have also be very successful...

  13. Continuing harmonization of terminology and innovations for methodologies in developmental toxicology: Report of the 8th Berlin Workshop on Developmental Toxicity, 14-16 May 2014. (United States)

    Solecki, Roland; Rauch, Martina; Gall, Andrea; Buschmann, Jochen; Clark, Ruth; Fuchs, Antje; Kan, Haidong; Heinrich, Verena; Kellner, Rupert; Knudsen, Thomas B; Li, Weihua; Makris, Susan L; Ooshima, Yojiro; Paumgartten, Francisco; Piersma, Aldert H; Schönfelder, Gilbert; Oelgeschläger, Michael; Schaefer, Christof; Shiota, Kohei; Ulbrich, Beate; Ding, Xuncheng; Chahoud, Ibrahim


    This article is a report of the 8th Berlin Workshop on Developmental Toxicity held in May 2014. The main aim of the workshop was the continuing harmonization of terminology and innovations for methodologies used in the assessment of embryo- and fetotoxic findings. The following main topics were discussed: harmonized categorization of external, skeletal, visceral and materno-fetal findings into malformations, variations and grey zone anomalies, aspects of developmental anomalies in humans and laboratory animals, and innovations for new methodologies in developmental toxicology. The application of Version 2 terminology in the DevTox database was considered as a useful improvement in the categorization of developmental anomalies. Participants concluded that initiation of a project for comparative assessments of developmental anomalies in humans and laboratory animals could support regulatory risk assessment and university-based training. Improvement of new methodological approaches for alternatives to animal testing should be triggered for a better understanding of developmental outcomes.

  14. Characterization of a developmental toxicity dose-response model.


    Faustman, E M; Wellington, D G; Smith, W P; Kimmel, C A


    The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included ...

  15. 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.

  16. Computational Laboratory (United States)

    Federal Laboratory Consortium — This laboratory contains a number of commercial off-the-shelf and in-house software packages allowing for both statistical analysis as well as mathematical modeling...

  17. Analytical Laboratories (United States)

    Federal Laboratory Consortium — NETL’s analytical laboratories in Pittsburgh, PA, and Albany, OR, give researchers access to the equipment they need to thoroughly study the properties of materials...

  18. Laboratory Tests (United States)

    Laboratory tests check a sample of your blood, urine, or body tissues. A technician or your doctor ... compare your results to results from previous tests. Laboratory tests are often part of a routine checkup ...

  19. Epigenetic biomarkers in liver cancer. (United States)

    Banaudha, Krishna K; Verma, Mukesh


    Liver cancer (hepatocellular carcinoma or HCC) is a major cancer worldwide. Research in this field is needed to identify biomarkers that can be used for early detection of the disease as well as new approaches to its treatment. Epigenetic biomarkers provide an opportunity to understand liver cancer etiology and evaluate novel epigenetic inhibitors for treatment. Traditionally, liver cirrhosis, proteomic biomarkers, and the presence of hepatitis viruses have been used for the detection and diagnosis of liver cancer. Promising results from microRNA (miRNA) profiling and hypermethylation of selected genes have raised hopes of identifying new biomarkers. Some of these epigenetic biomarkers may be useful in risk assessment and for screening populations to identify who is likely to develop cancer. Challenges and opportunities in the field are discussed in this chapter.

  20. Biomarkers in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bennike, Tue; Birkelund, Svend; Stensballe, Allan


    with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future...... development of preventive and treatment strategies. Thus, the clinical use of a panel of biomarkers represents a diagnostic and prognostic tool of potentially great value. The technological development in recent years within proteomic research (determination and quantification of the complete protein content......) has made the discovery of novel biomarkers feasible. Several IBD-associated protein biomarkers are known, but none have been successfully implemented in daily use to distinguish CD and UC patients. The intestinal tissue remains an obvious place to search for novel biomarkers, which blood, urine...

  1. Update on Biomarkers for the Detection of Endometriosis

    Directory of Open Access Journals (Sweden)

    Amelie Fassbender


    Full Text Available Endometriosis is histologically characterized by the displacement of endometrial tissue to extrauterine locations including the pelvic peritoneum, ovaries, and bowel. An important cause of infertility and pelvic pain, the individual and global socioeconomic burden of endometriosis is significant. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7–11 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae and represents a clear research priority. In this review, we describe and discuss the current status of biomarkers of endometriosis in plasma, urine, and endometrium.

  2. Copper toxicity induced hepatocerebral and neurodegenerative diseases: an urgent need for prognostic biomarkers. (United States)

    Pal, Amit


    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.

  3. Biomarker evidence for Archean oxygen fluxes (Invited) (United States)

    Hallmann, C.; Waldbauer, J.; Sherman, L. S.; Summons, R. E.


    Knowledge of deep-time organismic diversity may be gained from the study of preserved sedimentary lipids with taxonomic specificity, i.e. biomarker hydrocarbons (e.g. Brocks and Summons, 2003; Waldbauer et al., 2009). As a consequence of long residence times and high thermal maturities however, biomarker concentrations are extremely low in most ancient (Precambrian) sediment samples, making them exceptionally prone to contamination during drilling, sampling and laboratory workup (e.g. Brocks et al., 2008). Outcrop samples most always carry a modern overprint and deep-time biogeochemistry thus relies on drilling operations to retrieve ‘clean’ sediment cores. One such effort was initiated by NASA’s Astrobiology Institute (NAI): the Archean biosphere drilling project (ABDP). We here report on the lipids retrieved from sediment samples in drill hole ABDP-9. Strong heterogeneities of extractable organic matter - both on a spatial scale and in free- vs. mineral-occluded bitumen - provide us with an opportunity to distinguish indigenous lipids from contaminants introduced during drilling. Stratigraphic trends in biomarker data for mineral-occluded bitumens are complementary to previously reported data (e.g. S- and N-isotopes, molybdenum enrichments) from ABDP-9 sediments (Anbar et al., 2007; Kaufman et al., 2007; Garvin et al., 2009) and suggest periodic fluxes of oxygen before the great oxidation event. Anbar et al. A whiff of oxygen before the great oxidation event. Science 317 (2007), 1903-1906. Brocks & Summons. Sedimentary hydrocarbons, biomarkers for early life. In: Schlesinger (Ed.) Treatise on Geochemistry, Vol. 8 (2003), 63-115. Brocks et al. Assessing biomarker syngeneity using branched alkanes with quaternary carbon (BAQCs) and other plastic contaminants. Geochimica et Cosmochimica Acta 72 (2008), 871-888. Garvin et al. Isotopic evidence for a aerobic nitrogen cycle in the latest Archean. Science 323 (2009), 1045-1048. Kaufman et al. Late Archean

  4. Consumo alimentar de Chrysoperla externa sobre as diferentes fases de desenvolvimento de Dysmicoccus brevipes, em laboratório Food consumption of Chrysoperla externa in different developmental phases of Dysmicoccus brevipes, under laboratory conditions

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Rodrigues Gonçalves-Gervásio


    Full Text Available Estudou-se o consumo e preferência alimentar de larvas de Chrysoperla externa Hagen, 1861 (Neuroptera: Chrysopidae em laboratório à temperatura de 25±2°C, 70±10% UR e 12 horas de fotofase, utilizando como presa a cochonilha-do-abacaxi (Dysmicoccus brevipes Cockerell, 1893, Hemiptera: Pseudococcidae. Durante a fase larval do predador foram consumidas, em média, 70, 50 e 15,8 cochonilhas do primeiro, segundo e terceiro ínstar, respectivamente, e 10 fêmeas adultas, num total de 145,8 indivíduos. Do número total de cochonilhas, 51% foram consumidos durante o terceiro ínstar do predador. O alto número de cochonilhas consumido demonstra que a C. externa apresenta potencial para ser utilizada no controle biológico da cochonilha D. brevipes.The food consumption and preference of larvae of Chrysoperla externa Hagen, 1861 (Neuroptera: Chrysopidae larval were studied in laboratory under 25±2°C, 70±10% RH and 12 hours photophase, utilizing the pineapple mealybug (Dysmicoccus brevipes Cockerell, 1893, Hemiptera: Pseudococcidae as a prey. The results showed that the predator's larval phases consumed on average of 70, 50 and 15,8 mealybugs of the first, second and third instar, respectively, and 10 adult females amounting to 145,8 individuals. It was noticed that 51% of the total number of mealybugs were consumed during the predator third instar. The high number of mealybugs consumed shows that C. externa presents a potential to be utilized in biological control of the mealybug D. brevipes.

  5. Biomarkers for lymphoma (United States)

    Zangar, Richard C.; Varnum, Susan M.


    A biomarker, method, test kit, and diagnostic system for detecting the presence of lymphoma in a person are disclosed. The lymphoma may be Hodgkin's lymphoma or non-Hodgkin's lymphoma. The person may be a high-risk subject. In one embodiment, a plasma sample from a person is obtained. The level of at least one protein listed in Table S3 in the plasma sample is measured. The level of at least one protein in the plasma sample is compared with the level in a normal or healthy subject. The lymphoma is diagnosed based upon the level of the at least one protein in the plasma sample in comparison to the normal or healthy level.

  6. Molecular biomarkers of neurodegeneration. (United States)

    Höglund, Kina; Salter, Hugh


    Neuronal dysfunction and degeneration are central events of a number of major diseases with significant unmet need. Neuronal dysfunction may not necessarily be the result of cell death, but may also be due to synaptic damage leading to impaired neuronal cell signaling or long-term potentiation. Once degeneration occurs, it is unclear whether axonal or synaptic loss comes first or whether this precedes neuronal cell death. In this review we summarize the pathophysiology of four major neurodegenerative diseases; Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig's disease) For each of these diseases, we describe how biochemical biomarkers are currently understood in relation to the pathophysiology and in terms of neuronal biology, and we discuss the clinical and diagnostic utility of these potential tools, which are at present limited. We discuss how markers may be used to drive drug development and clinical practice.

  7. Inflammatory biomarkers for AMD. (United States)

    Stanton, Chloe M; Wright, Alan F


    Age-related macular degeneration (AMD) is the leading cause of blindness worldwide, affecting an estimated 50 million individuals aged over 65 years.Environmental and genetic risk-factors implicate chronic inflammation in the etiology of AMD, contributing to the formation of drusen, retinal pigment epithelial cell dysfunction and photoreceptor cell death. Consistent with a role for chronic inflammation in AMD pathogenesis, several inflammatory mediators, including complement components, chemokines and cytokines, are elevated at both the local and systemic levels in AMD patients. These mediators have diverse roles in the alternative complement pathway, including recruitment of inflammatory cells, activation of the inflammasome, promotion of neovascularisation and in the resolution of inflammation. The utility of inflammatory biomarkers in assessing individual risk and progression of the disease is controversial. However, understanding the role of these inflammatory mediators in AMD onset, progression and response to treatment may increase our knowledge of disease pathogenesis and provide novel therapeutic options in the future.

  8. Biomarkers in the pathogenesis, diagnosis, and treatment of psoriasis

    Directory of Open Access Journals (Sweden)

    Molteni S


    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

  9. Developmental disorders of vision. (United States)

    Galaburda, Albert M; Duchaine, Bradley C


    This review of developmental disorders of vision focuses on only a few of the many disorders that disrupt visual development. Given the enormity of the human visual system in the primate brain and complexity of visual development, however, there are likely hundreds or thousands of types of disorders affecting high-level vision. The rapid progress seen in developmental dyslexia and WMS demonstrates the possibilities and difficulties inherent in researching such disorders, and the authors hope that similar progress will be made for congenital prosopagnosia and other disorders in the near future.

  10. [Novel biomarkers for diabetic nephropathy]. (United States)

    Araki, Shin-ichi


    Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. An early clinical sign of this complication is an increase of urinary albumin excretion, called microalbuminuria, which is not only a predictor of the progression of nephropathy, but also an independent risk factor for cardiovascular disease. Although microalbuminuria is clinically important to assess the prognosis of diabetic patients, it may be insufficient as an early and specific biomarker of diabetic nephropathy because of a large day-to-day variation and lack of a good correlation of microalbuminuria with renal dysfunction and pathohistological changes. Thus, more sensitive and specific biomarkers are needed to improve the diagnostic capability of identifying patients at high risk. The factors involved in renal tubulo-interstitial damage, the production and degradation of extracellular matrix, microinflammation, etc., are investigated as candidate molecules. Despite numerous efforts so far, the assessment of these biomarkers is still a subject of ongoing investigations. Recently, a variety of omics and quantitative techniques in systems biology are rapidly emerging in the field of biomarker discovery, including proteomics, transcriptomics, and metabolomics, and they have been applied to search for novel putative biomarkers of diabetic nephropathy. Novel biomarkers or their combination with microalbuminuria provide a better diagnostic accuracy than microalbuminuria alone, and may be useful for establishing personal medicine. Furthermore, the identification of novel biomarkers may provide insight into the mechanisms underlying diabetic nephropathy.

  11. Biomarkers in Multiple Sclerosis: An Up-to-Date Overview

    Directory of Open Access Journals (Sweden)

    Serafeim Katsavos


    Full Text Available During the last decades, the effort of establishing satisfactory biomarkers for multiple sclerosis has been proven to be very difficult, due to the clinical and pathophysiological complexities of the disease. Recent knowledge acquired in the domains of genomics-immunogenetics and neuroimmunology, as well as the evolution in neuroimaging, has provided a whole new list of biomarkers. This variety, though, leads inevitably to confusion in the effort of decision making concerning strategic and individualized therapeutics. In this paper, our primary goal is to provide the reader with a list of the most important characteristics that a biomarker must possess in order to be considered as reliable. Additionally, up-to-date biomarkers are further divided into three subgroups, genetic-immunogenetic, laboratorial, and imaging. The most important representatives of each category are presented in the text and for the first time in a summarizing workable table, in a critical way, estimating their diagnostic potential and their efficacy to correlate with phenotypical expression, neuroinflammation, neurodegeneration, disability, and therapeutical response. Special attention is given to the “gold standards” of each category, like HLA-DRB1* polymorphisms, oligoclonal bands, vitamin D, and conventional and nonconventional imaging techniques. Moreover, not adequately established but quite promising, recently characterized biomarkers, like TOB-1 polymorphisms, are further discussed.

  12. Development of Parkinson's disease biomarkers. (United States)

    Prakash, Kumar M; Tan, Eng-King


    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.

  13. The NINDS Parkinson's disease biomarkers program: The Ninds Parkinson's Disease Biomarkers Program

    Energy Technology Data Exchange (ETDEWEB)

    Rosenthal, Liana S. [Department of Neurology, Johns Hopkins University School of Medicine, Baltimore Maryland USA; Drake, Daniel [Department of Biostatistics, Columbia University, New York New York USA; Alcalay, Roy N. [Department of Neurology, Columbia University, New York New York USA; Babcock, Debra [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Bowman, F. DuBois [Department of Biostatistics, Columbia University, New York New York USA; Chen-Plotkin, Alice [Department of Neurology, University of Pennsylvania, Philadelphia Pennsylvania USA; Dawson, Ted M. [Department of Neurology, Johns Hopkins University School of Medicine, Baltimore Maryland USA; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Solomon H. Snyder Department of Neuroscience, Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore Maryland USA; Dewey, Richard B. [Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas USA; German, Dwight C. [Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas USA; Huang, Xuemei [Department of Neurology, Penn State Hershey Medical Center, Hershey Pennsylvania USA; Landin, Barry [Center for Information Technology, National Institutes of Health, Bethesda Maryland USA; McAuliffe, Matthew [Center for Information Technology, National Institutes of Health, Bethesda Maryland USA; Petyuk, Vladislav A. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland Washington USA; Scherzer, Clemens R. [Department of Neurology, Brigham & Women' s Hospital, Harvard Medical School, Cambridge Massachusetts USA; Hillaire-Clarke, Coryse St. [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Sieber, Beth-Anne [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Sutherland, Margaret [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Tarn, Chi [Coriell Institute for Medical Research, Camden New Jersey USA; West, Andrew [Department of Neurology, University of Alabama at Birmingham, Birmingham USA; Vaillancourt, David [Department of Applied Physiology and Kinesiology, University of Florida, Gainesville Florida USA; Zhang, Jing [Department of Pathology, University of Washington, Seattle Washington USA; Gwinn, Katrina [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA


    Background: Neuroprotection for Parkinson Disease (PD) remains elusive. Biomarkers hold the promise of removing roadblocks to therapy development. The National Institute of Neurological Disorders and Stroke (NINDS) has therefore established the Parkinson’s Disease Biomarkers Program (PDBP) to promote discovery of biomarkers for use in phase II-III clinical trials in PD. Methods: The PDBP facilitates biomarker development to improve neuroprotective clinical trial design, essential for advancing therapeutics for PD. To date, eleven consortium projects in the PDBP are focused on the development of clinical and laboratory-based PD biomarkers for diagnosis, progression tracking, and/or the prediction of prognosis. Seven of these projects also provide detailed longitudinal data and biospecimens from PD patients and controls, as a resource for all PD researchers. Standardized operating procedures and pooled reference samples have been created in order to allow cross-project comparisons and assessment of batch effects. A web-based Data Management Resource facilitates rapid sharing of data and biosamples across the entire PD research community for additional biomarker projects. Results: Here we describe the PDBP, highlight standard operating procedures for the collection of biospecimens and data, and provide an interim report with quality control analysis on the first 1082 participants and 1033 samples with quality control analysis collected as of October 2014. Conclusions: By making samples and data available to academics and industry, encouraging the adoption of existing standards, and providing a resource which complements existing programs, the PDBP will accelerate the pace of PD biomarker research, with the goal of improving diagnostic methods and treatment.

  14. Cognitive impairment and major depressive disorder in HIV infection and cerebrospinal fluid biomarkers. (United States)

    Almeida, Sérgio Monteiro de


    Cognitive impairment and major depressive disorder (MDD) are common HIV-1 central nervous system (CNS) complications. Their frequencies in AIDS patients are 36% and 45%, respectively. The diagnoses of HIV cognitive impairment are made by clinical criteria, no single laboratory test or biomarker establishes the diagnosis. Factors of indirect neuronal injury related with the pathophysiology of the HIV infection in the CNS, are the factors studied as biomarkers. In the present no biomarker is established to the diagnosis of HIV cognitive impairment, much still needs to be done. We review in this paper some biomarkers in cerebrospinal fluid that could be valuable to the diagnosis of HIV cognitive impairment. Diagnosing depression in the context of HIV can be challenging, to identify a biomarker that could help in the diagnosis would be very important, although MDD risks and neurobiology are still poorly understood.

  15. Cognitive impairment and major depressive disorder in HIV infection and cerebrospinal fluid biomarkers

    Directory of Open Access Journals (Sweden)

    Sergio Monteiro de Almeida


    Full Text Available Cognitive impairment and major depressive disorder (MDD are common HIV-1 central nervous system (CNS complications. Their frequencies in AIDS patients are 36% and 45%, respectively. The diagnoses of HIV cognitive impairment are made by clinical criteria, no single laboratory test or biomarker establishes the diagnosis. Factors of indirect neuronal injury related with the pathophysiology of the HIV infection in the CNS, are the factors studied as biomarkers. In the present no biomarker is established to the diagnosis of HIV cognitive impairment, much still needs to be done. We review in this paper some biomarkers in cerebrospinal fluid that could be valuable to the diagnosis of HIV cognitive impairment. Diagnosing depression in the context of HIV can be challenging, to identify a biomarker that could help in the diagnosis would be very important, although MDD risks and neurobiology are still poorly understood.

  16. Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update. (United States)

    del Campo, Marta; Mollenhauer, Brit; Bertolotto, Antonio; Engelborghs, Sebastiaan; Hampel, Harald; Simonsen, Anja Hviid; Kapaki, Elisabeth; Kruse, Niels; Le Bastard, Nathalie; Lehmann, Sylvain; Molinuevo, Jose L; Parnetti, Lucilla; Perret-Liaudet, Armand; Sáez-Valero, Javier; Saka, Esen; Urbani, Andrea; Vanmechelen, Eugeen; Verbeek, Marcel; Visser, Pieter Jelle; Teunissen, Charlotte


    Early diagnosis of neurodegenerative disorders such as Alzheimer's (AD) or Parkinson's disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging due to the high variability found between centers in the concentrations of both AD CSF biomarkers (Aβ42, total tau and phosphorylated tau) and PD CSF biomarker (α-synuclein). Such a variability has been partially attributed to different preanalytical procedures between laboratories, thus highlighting the need to establish standardized operating procedures. Here, we merge two previous consensus guidelines for preanalytical confounding factors in order to achieve one exhaustive guideline updated with new evidence for Aβ42, total tau and phosphorylated tau, and α-synuclein. The proposed standardized operating procedures are applicable not only to novel CSF biomarkers in AD and PD, but also to biomarkers for other neurodegenerative disorders.

  17. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing


    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  18. Arguments from Developmental Order. (United States)

    Stöckle-Schobel, Richard


    In this article, I investigate a special type of argument regarding the role of development in theorizing about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind - getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories. Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasizing the importance of the early cognitive processes and arguments emphasizing the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive) development, and I will present some topics that also pertain to a full-fledged 'philosophy of development.'

  19. Laboratory Building.

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, Joshua M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    This report is an analysis of the means of egress and life safety requirements for the laboratory building. The building is located at Sandia National Laboratories (SNL) in Albuquerque, NM. The report includes a prescriptive-based analysis as well as a performance-based analysis. Following the analysis are appendices which contain maps of the laboratory building used throughout the analysis. The top of all the maps is assumed to be north.

  20. Laboratory Building

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, Joshua M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    This report is an analysis of the means of egress and life safety requirements for the laboratory building. The building is located at Sandia National Laboratories (SNL) in Albuquerque, NM. The report includes a prescriptive-based analysis as well as a performance-based analysis. Following the analysis are appendices which contain maps of the laboratory building used throughout the analysis. The top of all the maps is assumed to be north.

  1. Developmental Purposes of Commercial Games. (United States)

    Practical Pointers, 1977


    Listed are 45 table, target, manipulative, active, and creative games with such developmental purposes as associative learning, tactile discrimination, and visual motor integration. Information includes the name of the item, distributor, price, description, and developmental purpose. (JYC)

  2. Qualitative methodology in developmental psychology

    DEFF Research Database (Denmark)

    Demuth, Carolin; Mey, Günter


    Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing...

  3. Dynamics Laboratory (United States)

    Federal Laboratory Consortium — The Dynamics Lab replicates vibration environments for every Navy platform. Testing performed includes: Flight Clearance, Component Improvement, Qualification, Life...

  4. Visualization Laboratory (United States)

    Federal Laboratory Consortium — FUNCTION: Evaluates and improves the operational effectiveness of existing and emerging electronic warfare systems. By analyzing and visualizing simulation results...

  5. Propulsion Laboratory (United States)

    Federal Laboratory Consortium — The Propulsion Lab simulates field test conditions in a controlled environment, using standardized or customized test procedures. The Propulsion Lab's 11 cells can...

  6. Chemistry Laboratory (United States)

    Federal Laboratory Consortium — Purpose: To conduct fundamental studies of highway materials aimed at understanding both failure mechanisms and superior performance. New standard test methods are...

  7. Psychology Laboratory (United States)

    Federal Laboratory Consortium — This facility provides testing stations for computer-based assessment of cognitive and behavioral Warfighter performance. This 500 square foot configurable space can...

  8. Analytical Laboratory (United States)

    Federal Laboratory Consortium — The Analytical Labspecializes in Oil and Hydraulic Fluid Analysis, Identification of Unknown Materials, Engineering Investigations, Qualification Testing (to support...

  9. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An


    Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

  10. Procalcitonine als biomarker voor infecties

    NARCIS (Netherlands)

    de Jonge, J C; de Lange, D W; Bij de Vaate, E A; van Leeuwen, H; Arends, J E


    - Inappropriate use of antibiotics in patients without bacterial infection contributes significantly to worldwide antibiotic resistance.- The goal of this review is to summarise evidence from randomised trials investigating the value of the biomarker procalcitonin (PCT) in patients with symptoms of

  11. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille


    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  12. Biomarkers in Prostate Cancer Epidemiology


    Mudit Verma; Mukesh Verma; Payal Patel


    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 ris...

  13. Biomarkers of satiation and satiety. (United States)

    de Graaf, Cees; Blom, Wendy A M; Smeets, Paul A M; Stafleu, Annette; Hendriks, Henk F J


    This review's objective is to give a critical summary of studies that focused on physiologic measures relating to subjectively rated appetite, actual food intake, or both. Biomarkers of satiation and satiety may be used as a tool for assessing the satiating efficiency of foods and for understanding the regulation of food intake and energy balance. We made a distinction between biomarkers of satiation or meal termination and those of meal initiation related to satiety and between markers in the brain [central nervous system (CNS)] and those related to signals from the periphery to the CNS. Various studies showed that physicochemical measures related to stomach distension and blood concentrations of cholecystokinin and glucagon-like peptide 1 are peripheral biomarkers associated with meal termination. CNS biomarkers related to meal termination identified by functional magnetic resonance imaging and positron emission tomography are indicators of neural activity related to sensory-specific satiety. These measures cannot yet serve as a tool for assessing the satiating effect of foods, because they are not yet feasible. CNS biomarkers related to satiety are not yet specific enough to serve as biomarkers, although they can distinguish between extreme hunger and fullness. Three currently available biomarkers for satiety are decreases in blood glucose in the short term (2-4 d) negative energy balance; and ghrelin concentrations, which have been implicated in both short-term and long-term energy balance. The next challenge in this research area is to identify food ingredients that have an effect on biomarkers of satiation, satiety, or both. These ingredients may help consumers to maintain their energy intake at a level consistent with a healthy body weight.

  14. Analysis of biomarker data a practical guide

    CERN Document Server

    Looney, Stephen W


    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

  15. Optimizing a waveguide-based sandwich immunoassay for tumor biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Mukundan, Harshini [Los Alamos National Laboratory; Swanson, Basil I [Los Alamos National Laboratory; Xie, Hongzhi [Los Alamos National Laboratory; Anderson, Aaron S [Los Alamos National Laboratory; Grace, W Kevin [Los Alamos National Laboratory; Shively, John E [NON LANL


    The sensor team at the Los Alamos National Laboratory has developed a waveguide-based optical biosensor for the detection of biomarkers associated with the disease. We have previously demonstrated the application of this technology to the sensitive detection of carcinoembryonic antigen in serum and nipple aspirate fluid from breast cancer patients. In this publication, we report improvements to this technology that will facilitate transition to a point-of-care diagnostic system and/or robust research tool.

  16. Learning Laboratory. (United States)

    Hay, Lyn; Callison, Daniel


    Considers the school library media center as an information learning laboratory. Topics include information literacy; Kuhlthau's Information Search Process model; inquiry theory and approach; discovery learning; process skills of laboratory science; the information scientist; attitudes of media specialists, teachers, and students; displays and Web…

  17. TRWG developmental pathway for biospecimen-based assessment modalities

    Energy Technology Data Exchange (ETDEWEB)

    Translational Research Working Group; Srivastava, Sudhir; Gray, Joe W.; Reid, Brian J.; Grad, Oren; Greenwood, Addison; Hawk, Ernest T.


    The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of NCI's investment in translational research and envision its future. The TRWG conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of biospecimen-based assays that utilize biomarkers for the detection, diagnosis, prognosis, and assessment of response to cancer treatment. The biospecimen-based assessment modality (BM) pathway was conceived not as comprehensive description of the corresponding real-world processes, but rather as a tool designed to facilitate movement of a candidate assay through the translational process to the point where it can be handed off for definitive clinical testing. This paper introduces the pathway in the context of prior work and discusses key challenges associated with the biomarker development process in light of the pathway.

  18. Biomarkers for PTSD (United States)


    anxiety disorders. Ressler hopes that by understanding how fear works in the mammalian brain in the laboratory, it will improve understanding of and...provide translational treatments and possibly prevention for fear-based disorders, such as PTSD, phobic disorders and panic disorder. Dr. Ressler...PROVE (Project for Return and Opportunity in Veterans Education) Queens Vet Center Rutgers Anxiety Disorders Clinic Veteran PTSD Support Group

  19. Developmental Gerstmann's syndrome. (United States)

    PeBenito, R; Fisch, C B; Fisch, M L


    The tetrad of finger agnosia, dysgraphia, dyscalculia, and right-left disorientation make up Gerstmann's syndrome. The tetrad has been infrequently described in children with learning disability and has been called developmental Gerstmann's syndrome (DGS). Developmental Gerstmann's syndrome may occur in brain-damaged and apparently normal children. Five children in whom DGS occurred in association with brain abnormalities underwent long-term observation, which indicated persistence of the deficits. The identification of these cases suggests that DGS may not be as rare as previously thought and may often be unrecognized. Testing for the Gerstmann elements in learning-disabled children may identify otherwise undiagnosed cases of DGS and should be routinely employed in the neurologic examination. Until appropriate teaching methods for DGS are found, "bypassing" the deficits and utilizing the child's strengths, plus counseling, seem to offer an effective treatment approach.

  20. Developmental genetics in emerging rodent models: case studies and perspectives. (United States)

    Mallarino, Ricardo; Hoekstra, Hopi E; Manceau, Marie


    For decades, mammalian developmental genetic studies have focused almost entirely on two laboratory models: Mus and Rattus, species that breed readily in the laboratory and for which a wealth of molecular and genetic resources exist. These species alone, however, do not capture the remarkable diversity of morphological, behavioural and physiological traits seen across rodents, a group that represents >40% of all mammal species. Due to new advances in molecular tools and genomic technologies, studying the developmental events underlying natural variation in a wide range of species for a wide range of traits has become increasingly feasible. Here we review several recent studies and discuss how they not only provided technical resources for newly emerging rodent models in developmental genetics but also are instrumental in further encouraging scientists, from a wide range of research fields, to capitalize on the great diversity in development that has evolved among rodents.

  1. Developmental Toxicity of Louisiana Crude Oil-Spiked Sediment to Zebrafish (United States)

    Embryonic exposures to the components of petroleum, including polycyclic aromatic hydrocarbons (PAHs), cause a characteristic suite of developmental defects and cardiotoxicity in a variety of fish species. We exposed zebrafish embryos to reference sediment mixed with laboratory w...

  2. Developmental Partial Differential Equations


    Duteil, Nastassia Pouradier; Rossi, Francesco; Boscain, Ugo; Piccoli, Benedetto


    In this paper, we introduce the concept of Developmental Partial Differential Equation (DPDE), which consists of a Partial Differential Equation (PDE) on a time-varying manifold with complete coupling between the PDE and the manifold's evolution. In other words, the manifold's evolution depends on the solution to the PDE, and vice versa the differential operator of the PDE depends on the manifold's geometry. DPDE is used to study a diffusion equation with source on a growing surface whose gro...

  3. NIDCAP and developmental care

    Directory of Open Access Journals (Sweden)

    Dominique Haumont


    Full Text Available Perinatal mortality in very low birth weight infants has dramatically decreased during the last decades. However, 15-25% of these infants will show neurodevelopmental impairment later on. The aim of implementing early developmental care (EDC, emerged as a new field in neonatology, is to create an intervention program designed to provide support for optimal neurobehavioral development during this highly vulnerable period of brain growth. The theoretical framework, which underlies the approach, is supported by research in different scientific fields, including neuroscience, psychology, medicine and nursing. EDC utilizes a range of medical and nursing interventions that aim to decrease the stress of preterm neonates in neonatal intensive care units (NICUs. The Neonatal Individualized Developmental Care Assessment Program (NIDCAP is an integrated and holistic form of family-centered developmental care. Changing the traditional NICU towards an EDC-NICU includes training nursing and medical staff, investing in their quality and most importantly keeping parents in proximity to the infants. The new challenge of modern neonatology is to restore the mother-infant dyad applying “couplet care” starting at birth until discharge. Most of the European NICUs apply some elements of EDC, but it is more consistent in northern Europe. The development of NIDCAP training centers in Europe demonstrates the evolution of care. It is likely that future research and intervention programs will optimize our practices. Developmental care could prove to be an important recent step in improving outcome in extremely preterm neonates. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  4. Developmental dyslexia and vision



    Patrick Quercia,1 Léonard Feiss,2 Carine Michel31Department of Ophthalmology, University Hospital, Dijon, France; 2Office of Ophthalmology, Beaune, France; 3University of Burgundy, Dijon, INSERM U1093, Cognition, Action et Plasticité Sensorimotrice, Dijon, FranceAbstract: Developmental dyslexia affects almost 10% of school-aged children and represents a significant public health problem. Its etiology is unknown. The consistent presence of phonological difficulties combin...

  5. Variability of CSF Alzheimer's disease biomarkers: implications for clinical practice.

    Directory of Open Access Journals (Sweden)

    Stephanie J B Vos

    Full Text Available BACKGROUND: Cerebrospinal fluid (CSF biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD. OBJECTIVE: We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. METHODS: We measured CSF amyloid-β (Aβ 1-42, total tau (t-tau, and phosphorylated tau (p-tau by INNOTEST enzyme-linked-immunosorbent assays (ELISA in a memory clinic population (n = 126. Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern. RESULTS: CSF intralaboratory variability was higher for Aβ1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal of 26% of the subjects based on Aβ1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Aβ1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Aβ1-42, 1% based on t-tau, and 22% based on p-tau. CONCLUSIONS: Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Aβ1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice.

  6. Analytical Aspects of the Implementation of Biomarkers in Clinical Transplantation. (United States)

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


    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.

  7. Non-Small Cell Carcinoma Biomarker Testing: The Pathologist's Perspective.

    Directory of Open Access Journals (Sweden)

    Elisa eBrega


    Full Text Available Biomarker testing has become standard of care for patients diagnosed with non-small cell lung cancer. Although it can be successfully performed in circulating tu-mor cells, at present, the vast majority of investigations are carried out using di-rect tumor sampling, either through aspiration methods, which render most often isolated cells, or tissue sampling, that could range from minute biopsies to large resections. Consequently, pathologists play a central role in this process. Recent evidence suggests that refining NSCLC diagnosis might be clinically signifi-cant, particularly in cases of lung adenocarcinomas (ADC, which in turn, has prompted a new proposal for the histologic classification of such pulmonary neo-plasms. These changes, in conjunction with the mandatory incorporation of biomarker testing in routine NSCLC tissue processing, have directly affected the pathologist’s role in lung cancer work-up. This new role pathologists must play is complex and demanding, and requires a close interaction with surgeons, oncologists, radiologists and molecular pathologists. Pathologists often find themselves as the central figure in the coordination of a process, that involves assuring that the tumor samples are properly fixed, but without disruption of the DNA structure, obtaining the proper diagnosis with a minimum of tissue waste, providing pre-analytical evaluation of tumor samples selected for biomarker testing, which includes assessment of the proportion of tumor to normal tissues, as well as cell viability, and assuring that this entire pro-cess happens in a timely fashion. Therefore, it is part of the pathologist’s respon-sibilities to assure that the samples received in their laboratories, be processed in a manner that allows for optimal biomarker testing. This article goal is to discuss the essential role pathologists must play NSCLC bi-omarker testing, as well as to provide a summarized review of the main NSCLC bi-omarkers of

  8. Evolutionary developmental psychology. (United States)

    King, Ashley C; Bjorklund, David F


    The field of evolutionary developmental psychology can potentially broaden the horizons of mainstream evolutionary psychology by combining the principles of Darwinian evolution by natural selection with the study of human development, focusing on the epigenetic effects that occur between humans and their environment in a way that attempts to explain how evolved psychological mechanisms become expressed in the phenotypes of adults. An evolutionary developmental perspective includes an appreciation of comparative research and we, among others, argue that contrasting the cognition of humans with that of nonhuman primates can provide a framework with which to understand how human cognitive abilities and intelligence evolved. Furthermore, we argue that several aspects of childhood (e.g., play and immature cognition) serve both as deferred adaptations as well as imparting immediate benefits. Intense selection pressure was surely exerted on childhood over human evolutionary history and, as a result, neglecting to consider the early developmental period of children when studying their later adulthood produces an incomplete picture of the evolved adaptations expressed through human behavior and cognition.

  9. EEG complexity as a biomarker for autism spectrum disorder risk

    Directory of Open Access Journals (Sweden)

    Tierney Adrienne


    Full Text Available Abstract Background Complex neurodevelopmental disorders may be characterized by subtle brain function signatures early in life before behavioral symptoms are apparent. Such endophenotypes may be measurable biomarkers for later cognitive impairments. The nonlinear complexity of electroencephalography (EEG signals is believed to contain information about the architecture of the neural networks in the brain on many scales. Early detection of abnormalities in EEG signals may be an early biomarker for developmental cognitive disorders. The goal of this paper is to demonstrate that the modified multiscale entropy (mMSE computed on the basis of resting state EEG data can be used as a biomarker of normal brain development and distinguish typically developing children from a group of infants at high risk for autism spectrum disorder (ASD, defined on the basis of an older sibling with ASD. Methods Using mMSE as a feature vector, a multiclass support vector machine algorithm was used to classify typically developing and high-risk groups. Classification was computed separately within each age group from 6 to 24 months. Results Multiscale entropy appears to go through a different developmental trajectory in infants at high risk for autism (HRA than it does in typically developing controls. Differences appear to be greatest at ages 9 to 12 months. Using several machine learning algorithms with mMSE as a feature vector, infants were classified with over 80% accuracy into control and HRA groups at age 9 months. Classification accuracy for boys was close to 100% at age 9 months and remains high (70% to 90% at ages 12 and 18 months. For girls, classification accuracy was highest at age 6 months, but declines thereafter. Conclusions This proof-of-principle study suggests that mMSE computed from resting state EEG signals may be a useful biomarker for early detection of risk for ASD and abnormalities in cognitive development in infants. To our knowledge, this is

  10. Mammalian developmental genetics in the twentieth century. (United States)

    Artzt, Karen


    This Perspectives is a review of the breathtaking history of mammalian genetics in the past century and, in particular, of the ways in which genetic thinking has illuminated aspects of mouse development. To illustrate the power of that thinking, selected hypothesis-driven experiments and technical advances are discussed. Also included in this account are the beginnings of mouse genetics at the Bussey Institute, Columbia University, and The Jackson Laboratory and a retrospective discussion of one of the classic problems in developmental genetics, the T/t complex and its genetic enigmas.

  11. Semiconductor Electrical Measurements Laboratory (United States)

    Federal Laboratory Consortium — The Semiconductor Electrical Measurements Laboratory is a research laboratory which complements the Optical Measurements Laboratory. The laboratory provides for Hall...

  12. Audio Laboratory (United States)

    Federal Laboratory Consortium — FUNCTION: Provides an environment and facilities for auditory display research. A primary focus is the performance use of binaurally rendered 3D sound in conjunction...

  13. Elastomers Laboratory (United States)

    Federal Laboratory Consortium — Primary capabilities include: elastomer compounding in various sizes (micro, 3x5, 8x12, 8x15 rubber mills); elastomer curing and post curing (two 50-ton presses, one...

  14. 南瓜寄主上扶桑绵粉蚧不同温度下的发育历期和实验种群生命表%Developmental duration and life table of the laboratory population of Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae ) fed on pumpkin at different temperatures

    Institute of Scientific and Technical Information of China (English)

    王莹莹; 徐志宏; 张莉丽; 沈励泽; 傅思丽


    为了探明温度对扶桑绵粉蚧Phenacoccus solenopsis Tinsley发育的影响,本研究在光周期14L:10D,相对湿度75%±1%及不同温度(18,20,24,26,28和30℃)的实验室条件下,测定了以南瓜为寄主的扶桑绵粉蚧各虫态的发育历期和存活率,组建了扶桑绵粉蚧的实验种群生命表.结果表明:在18 ~ 30℃温度范围内,随着温度的升高扶桑绵粉蚧的发育速率加快,且其温度与发育速率的关系符合Logistic模型.在18~30℃恒温条件下,扶桑绵粉蚧的雌虫世代发育历期为40.24 ~ 80.64 d,雄虫世代发育历期为25.21~54.31 d;雌虫世代的发育起点温度为7.39℃,有效积温为889.89日·度;雄虫世代的发育起点温度为8.58℃,有效积温为523.47日·度.在26℃时,扶桑绵粉蚧的世代存活率最高(77.03%),种群趋势指数也最高(22.98),有利于种群增长;而在18℃和30℃,扶桑绵粉蚧的种群趋势指数分别为2.99和9.80.扶桑绵粉蚧有较强的种群发展能力,但高温和低温都不利于其种群增长.扶桑绵粉蚧发育历期和实验种群表的研究为其控制措施的制定提供了科学依据.%In order to explore the effects of temperature on the population growth of the Phenacoccus solenopsis Tinsley fed on pumpkin, the developmental duration and survivorship were investigated under the temperatures of 18, 20, 24, 26, 28 and 30℃ , and the life table of the laboratory population of Ph. Solenopsis was constructed. The results showed that the developmental rate of Ph. Solenopsis increased with the temperature increasing from 18℃ to 30℃ , and the relationship between the developmental rate and temperature could be fitted well with the Logistic model. Within the temperature range of 18 -30t, the generation time of females and males was 40. 24 - 80. 64 d and 25. 21 - 54. 31 d, respectively. Thedevelopmental threshold temperature and effective accumulated temperature of females were 7. 39℃ and 889.89 day

  15. Developmental biology and tissue engineering. (United States)

    Marga, Francoise; Neagu, Adrian; Kosztin, Ioan; Forgacs, Gabor


    Morphogenesis implies the controlled spatial organization of cells that gives rise to tissues and organs in early embryonic development. While morphogenesis is under strict genetic control, the formation of specialized biological structures of specific shape hinges on physical processes. Tissue engineering (TE) aims at reproducing morphogenesis in the laboratory, i.e., in vitro, to fabricate replacement organs for regenerative medicine. The classical approach to generate tissues/organs is by seeding and expanding cells in appropriately shaped biocompatible scaffolds, in the hope that the maturation process will result in the desired structure. To accomplish this goal more naturally and efficiently, we set up and implemented a novel TE method that is based on principles of developmental biology and employs bioprinting, the automated delivery of cellular composites into a three-dimensional (3D) biocompatible environment. The novel technology relies on the concept of tissue liquidity according to which multicellular aggregates composed of adhesive and motile cells behave in analogy with liquids: in particular, they fuse. We emphasize the major role played by tissue fusion in the embryo and explain how the parameters (surface tension, viscosity) that govern tissue fusion can be used both experimentally and theoretically to control and simulate the self-assembly of cellular spheroids into 3D living structures. The experimentally observed postprinting shape evolution of tube- and sheet-like constructs is presented. Computer simulations, based on a liquid model, support the idea that tissue liquidity may provide a mechanism for in vitro organ building.

  16. Biomarkers of silicosis: Potential candidates

    Directory of Open Access Journals (Sweden)

    Tiwari R


    Full Text Available Silica dust is widely prevalent in the atmosphere and more common than the other types of dust, thus making silicosis the most frequently occurring pneumoconiosis. In India also, studies carried out by National Institute of Occupational Health have shown high prevalence of silicosis in small factories and even in nonoccupational exposed subjects. The postero-anterior chest radiographs remain the key tool in diagnosing and assessing the extent and severity of interstitial lung disease. Although Computed Tomography detects finer anatomical structure than radiography it could not get popularity because of its cost. On the basis of histological features of silicosis many potential biomarkers such as Cytokines, Tumor Necrosis Factor, Interleukin 1, Angiotensin Converting Enzyme, Serum Copper, Fas ligand (FasL, etc. have been tried. However, further studies are needed to establish these potential biomarkers as true biomarker of silicosis.

  17. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan


    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...

  18. Predicting Developmental Toxicity of ToxCast Phase I Chemicals Using Human Embryonic Stem Cells and Metabolomics (United States)

    EPA’s ToxRefDB contains prenatal guideline study data from rats and rabbits for over 240 chemicals that overlap with the ToxCast in vitro high throughput screening project. A subset of these compounds were tested in Stemina Biomarker Discovery's developmental toxicity platform, a...

  19. Peripheral biomarkers in Autism: secreted amyloid precursor protein-alpha as a probable key player in early diagnosis. (United States)

    Bailey, Antoinette R; Giunta, Brian N; Obregon, Demian; Nikolic, William V; Tian, Jun; Sanberg, Cyndy D; Sutton, Danielle T; Tan, Jun


    Autism is a pervasive developmental disorder characterized by impairments in socialization and communication. There is currently no single molecular marker or laboratory tool capable of diagnosing autism at an early age. The purpose of this study is to explore the plausible use of peripheral biomarkers in the early diagnosis of autism via a sensitive ELISA. Here, we measured plasma secreted amyloid precursor protein alpha (sAPP-alpha) levels in autistic and aged-matched control blood samples and found a significantly increased level of sAPP-alpha in 60% of the known autistic children. We then tested 150 human umbilical cord blood (HUCB) samples and found significantly elevated levels of plasma sAPP-alpha in 10 of 150 samples. As an additional confirmatory measure, we performed Western blot analysis on these samples which consistently showed increased sAPP-alpha levels in autistic children and 10 of 150 HUCB samples; suggesting a group of autistic patients which could be identified in early childhood by levels of sAPP-alpha. While there is need for further studies of this concept, the measurement of sAPP-alpha levels in serum and human umbilical cord blood by ELISA is a potential tool for early diagnosis of autism.

  20. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

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


    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...... sizes has been conducted. METHODS: Here, we performed a comprehensive review of meta-analyses of peripheral nongenetic biomarkers that could discriminate individuals with MDD from nondepressed controls. PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched through April 10, 2015. RESULTS: From 15...

  1. Proteomics in Discovery of Hepatocellular Carcinoma Biomarkers

    Institute of Scientific and Technical Information of China (English)


    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.

  2. Biomarker Detection using PS2-Thioaptamers Project (United States)

    National Aeronautics and Space Administration — AM Biotechnologies (AM) will develop a system to detect and quantify bone demineralization biomarkers as outlined in SBIR Topic "Technologies to Detect Biomarkers"....

  3. Mobile devices for the remote acquisition of physiological and behavioral biomarkers in psychiatric clinical research. (United States)

    W Adams, Zachary; McClure, Erin A; Gray, Kevin M; Danielson, Carla Kmett; Treiber, Frank A; Ruggiero, Kenneth J


    Psychiatric disorders are linked to a variety of biological, psychological, and contextual causes and consequences. Laboratory studies have elucidated the importance of several key physiological and behavioral biomarkers in the study of psychiatric disorders, but much less is known about the role of these biomarkers in naturalistic settings. These gaps are largely driven by methodological barriers to assessing biomarker data rapidly, reliably, and frequently outside the clinic or laboratory. Mobile health (mHealth) tools offer new opportunities to study relevant biomarkers in concert with other types of data (e.g., self-reports, global positioning system data). This review provides an overview on the state of this emerging field and describes examples from the literature where mHealth tools have been used to measure a wide array of biomarkers in the context of psychiatric functioning (e.g., psychological stress, anxiety, autism, substance use). We also outline advantages and special considerations for incorporating mHealth tools for remote biomarker measurement into studies of psychiatric illness and treatment and identify several specific opportunities for expanding this promising methodology. Integrating mHealth tools into this area may dramatically improve psychiatric science and facilitate highly personalized clinical care of psychiatric disorders.

  4. 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)


    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.

  5. Biomarkers of satiation and satiety

    NARCIS (Netherlands)

    Graaf, C. de; Blom, W.A.M.; Smeets, P.A.M.; Stafleu, A.; Hendriks, H.F.J.


    This review's objective is to give a critical summary of studies that focused on physiologic measures relating to subjectively rated appetite, actual food intake, or both. Biomarkers of satiation and satiety may be used as a tool for assessing the satiating efficiency of foods and for understanding

  6. Biomarkers in sarcoidosis: a review

    Directory of Open Access Journals (Sweden)

    Ahmadzai H


    Full Text Available Hasib Ahmadzai,1,2 Wei Sheng Joshua Loke,1 Shuying Huang,1 Cristan Herbert,1 Denis Wakefield,3 Paul S Thomas2 1Inflammation and Infection Research Centre (IIRC, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; 2Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, Sydney, NSW, Australia; 3Immunology of the Eye Clinic, St Vincent's Clinic, Darlinghurst, Sydney, NSW, Australia Abstract: Sarcoidosis is a systemic granulomatous disease of undetermined etiology invariably affecting the lungs and thoracic lymph nodes. It has been termed an “immune paradox”, as there is peripheral anergy despite exaggerated inflammation at disease sites. The disease is usually self-limiting, although some individuals experience unremitting inflammation that may progress into pulmonary fibrosis and death. The inflammatory process is largely a T helper-1-driven immune response. Given its heterogeneous clinical manifestations, diagnosis is usually a clinical conundrum. Clinical and radiological findings alone are often inadequate to confirm the diagnosis. At present, sarcoidosis is usually a diagnosis of exclusion, confirmed by histological evidence of noncaseating granulomas in the absence of known granulomagenic agents. This has compelled researchers to look for disease-specific biomarkers that can help diagnose sarcoidosis and delineate its disease course, severity, and prognosis. In this review we highlight various investigations used to diagnose sarcoidosis, outline proposed biomarkers, and discuss novel methods of sampling biomarkers. Keywords: sarcoidosis, biomarkers, inflammatory markers, exhaled breath condensate, proteomics, granuloma


    Directory of Open Access Journals (Sweden)

    Kolyada T.I


    Full Text Available Current data concerning features of multiple sclerosis (MS etiology, pathogenesis, clinical course and treatment of disease indicate the necessity of personalized approach to the management of MS patients. These features are the variety of possible etiological factors and mechanisms that trigger the development of MS, different courses of disease, and significant differences in treatment efficiency. Phenotypic and pathogenetic heterogeneity of MS requires, on the one hand, the stratification of patients into groups with different treatment depending on a number of criteria including genetic characteristics, disease course, stage of the pathological process, and forms of the disease. On the other hand, it requires the use of modern methods for assessment of individual risk of developing MS, its early diagnosis, evaluation and prognosis of the disease course and the treatment efficiency. This approach is based on the identification and determination of biomarkers of MS including the use of systems biology technology platforms such as genomics, proteomics, metabolomics and bioinformatics. Research and practical use of biomarkers of MS in clinical and laboratory practice requires the use of a wide range of modern medical and biological, mathematical and physicochemical methods. The group of "classical" methods used to study MS biomarkers includes physicochemical and immunological methods aimed at the selection and identification of single molecular biomarkers, as well as methods of molecular genetic analysis. This group of methods includes ELISA, western blotting, isoelectric focusing, immunohistochemical methods, flow cytometry, spectrophotometric and nephelometric methods. These techniques make it possible to carry out both qualitative and quantitative assay of molecular biomarkers. The group of "classical methods" can also include methods based on polymerase chain reaction (including multiplex and allele-specific PCR and genome sequencing

  8. Constructivist developmental theory is needed in developmental neuroscience (United States)

    Arsalidou, Marie; Pascual-Leone, Juan


    Neuroscience techniques provide an open window previously unavailable to the origin of thoughts and actions in children. Developmental cognitive neuroscience is booming, and knowledge from human brain mapping is finding its way into education and pediatric practice. Promises of application in developmental cognitive neuroscience rests however on better theory-guided data interpretation. Massive amounts of neuroimaging data from children are being processed, yet published studies often do not frame their work within developmental models—in detriment, we believe, to progress in this field. Here we describe some core challenges in interpreting the data from developmental cognitive neuroscience, and advocate the use of constructivist developmental theories of human cognition with a neuroscience interpretation.

  9. Biomarkers of (osteo)arthritis. (United States)

    Mobasheri, Ali; Henrotin, Yves


    Arthritic diseases are a major cause of disability and morbidity, and cause an enormous burden for health and social care systems globally. Osteoarthritis (OA) is the most common form of arthritis. The key risk factors for the development of OA are age, obesity, joint trauma or instability. Metabolic and endocrine diseases can also contribute to the pathogenesis of OA. There is accumulating evidence to suggest that OA is a whole-organ disease that is influenced by systemic mediators, inflammaging, innate immunity and the low-grade inflammation induced by metabolic syndrome. Although all joint tissues are implicated in disease progression in OA, articular cartilage has received the most attention in the context of aging, injury and disease. There is increasing emphasis on the early detection of OA as it has the capacity to target and treat the disease more effectively. Indeed it has been suggested that this is the era of "personalized prevention" for OA. However, the development of strategies for the prevention of OA require new and sensitive biomarker tools that can detect the disease in its molecular and pre-radiographic stage, before structural and functional alterations in cartilage integrity have occurred. There is also evidence to support a role for biomarkers in OA drug discovery, specifically the development of disease modifying osteoarthritis drugs. This Special Issue of Biomarkers is dedicated to recent progress in the field of OA biomarkers. The papers in this Special Issue review the current state-of-the-art and discuss the utility of OA biomarkers as diagnostic and prognostic tools.

  10. An inter-laboratory comparison of urinary 3-hydroxypropylmercapturic acid measurement demonstrates good reproducibility between laboratories

    Directory of Open Access Journals (Sweden)

    Bailey Brian


    Full Text Available Abstract Background Biomarkers have been used extensively in clinical studies to assess toxicant exposure in smokers and non-smokers and have recently been used in the evaluation of novel tobacco products. The urinary metabolite 3-HPMA, a metabolite of the major tobacco smoke toxicity contributor acrolein, is one example of a biomarker used to measure exposure to tobacco smoke. A number of laboratories have developed liquid chromatography with tandem mass spectrometry (LC-MS/MS based methods to measure urinary 3-HPMA; however, it is unclear to what extent the data obtained by these different laboratories are comparable. Findings This report describes an inter-laboratory comparison carried out to evaluate the comparability of 3-HPMA measurement between four laboratories. A common set of spiked and authentic smoker and non-smoker urine samples were used. Each laboratory used their in-house LC-MS/MS method and a common internal standard. A comparison of the repeatability ('r', reproducibility ('R', and coefficient of variation for 3-HPMA demonstrated that within-laboratory variation was consistently lower than between-laboratory variation. The average inter-laboratory coefficient of variation was 7% for fortified urine samples and 16.2% for authentic urine samples. Together, this represents an inter-laboratory variation of 12.2%. Conclusion The results from this first inter-laboratory comparison for the measurement of 3-HPMA in urine demonstrate a reasonably good consensus between laboratories. However, some consistent measurement biases were still observed between laboratories, suggesting that additional work may be required to further reduce the inter-laboratory coefficient of variation.

  11. Deep biomarkers of human aging: Application of deep neural networks to biomarker development. (United States)

    Putin, Evgeny; Mamoshina, Polina; Aliper, Alexander; Korzinkin, Mikhail; Moskalev, Alexey; Kolosov, Alexey; Ostrovskiy, Alexander; Cantor, Charles; Vijg, Jan; Zhavoronkov, Alex


    One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R(2) = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R(2) = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis.

  12. Cancer Biomarkers | Division of Cancer Prevention (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.

  13. Developmental Math: What's the Answer? (United States)

    Cafarella, Brian


    Developmental mathematics has been under the radar within higher education for some time. The reality is that there are many proven best practices in developmental math. Unfortunately, there are many obstacles that prevent student success. Moreover, the high rates of attrition and failure have led state legislators and college administrators to…

  14. [Developmental Placement.] Collected Research References. (United States)

    Bjorklund, Gail

    Drawing on information and references in the ERIC system, this literature review describes research related to a child's developmental placement. The issues examined include school entrance age; predictive validity, reliability, and features of Gesell School Readiness Assessment; retention; and the effectiveness of developmental placement. A…

  15. Developmental Sentence Scoring for Japanese (United States)

    Miyata, Susanne; MacWhinney, Brian; Otomo, Kiyoshi; Sirai, Hidetosi; Oshima-Takane, Yuriko; Hirakawa, Makiko; Shirai, Yasuhiro; Sugiura, Masatoshi; Itoh, Keiko


    This article reports on the development and use of the Developmental Sentence Scoring for Japanese (DSSJ), a new morpho-syntactical measure for Japanese constructed after the model of Lee's English Developmental Sentence Scoring model. Using this measure, the authors calculated DSSJ scores for 84 children divided into six age groups between 2;8…

  16. Saxton Transportation Operations Laboratory (United States)

    Federal Laboratory Consortium — The Saxton Transportation Operations Laboratory (Saxton Laboratory) is a state-of-the-art facility for conducting transportation operations research. The laboratory...

  17. Mining of hospital laboratory information systems

    DEFF Research Database (Denmark)

    Søeby, Karen; Jensen, Peter Bjødstrup; Werge, Thomas


    of hospital laboratory data as a source of information, we analyzed enzymatic plasma creatinine as a model analyte in two large pediatric hospital samples. Methods: Plasma creatinine measurements from 9700 children aged 0-18 years were obtained from hospital laboratory databases and partitioned into high......-resolution gender- and age-groups. Normal probability plots were used to deduce parameters of the normal distributions from healthy creatinine values in the mixed hospital datasets. Furthermore, temporal trajectories were generated from repeated measurements to examine developmental patterns in periods of changing...... in creatinine levels at different time points after birth and around the early teens, which challenges the establishment and usefulness of reference intervals in those age groups. Conclusions: The study documents that hospital laboratory data may inform on the developmental aspects of creatinine, on periods...

  18. Implementation of proteomic biomarkers: making it work (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


    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

  19. Incorporating biomarkers in ecological risk assessment of chemical contaminants of soils

    Directory of Open Access Journals (Sweden)

    A. J. Reinecke


    Full Text Available Soil is an important but complex natural resource which is increasingly used as sink for chemicals. The monitoring of soil quality and the assessment of risks posed by contaminants have become crucial. This study deals with the potential use of biomarkers in the monitoring of soils and the assessment of risk resulting from contamination. Apart from an overview of the existing literature on biomarkers, the results of various of our field experiments in South African soils are discussed. Biomarkers may have potential in the assessment of risk because they can indicate at an early stage that exposure has taken place and that a toxic response has been initiated. It is therefore expected that early biomarkers will play an increasing role as diagnostic tools for determining exposure to chemicals and the resulting effects. They may have predictive value that can assist in the prevention or minimising of risks. The aim of this study was to investigate the possibilities of using our results on biomarker responses of soil dwelling organisms to predict changes at higher organisational levels (which may have ecological implications. Our recent experimental results on the evaluation of various biomarkers in both the laboratory and the field are interpreted and placed in perspective within the broader framework of response biology. The aim was further to contribute to the development and application of biomarkers in regulatory risk assessment schemes of soils. This critical review of our own and recent literature on biomarkers in ecotoxicology leads to the conclusion that biomarkers can, under certain conditions, be useful tools in risk assessment. Clear relationships between contamination loads in soil organisms and certain biomarker responses were determined in woodlice, earthworms and terrestrial snails. Clear correlations were also established in field experiments between biomarker responses and changes at the population level. This indicated that, in

  20. Lunar laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Keaton, P.W.; Duke, M.B.


    An international research laboratory can be established on the Moon in the early years of the 21st Century. It can be built using the transportation system now envisioned by NASA, which includes a space station for Earth orbital logistics and orbital transfer vehicles for Earth-Moon transportation. A scientific laboratory on the Moon would permit extended surface and subsurface geological exploration; long-duration experiments defining the lunar environment and its modification by surface activity; new classes of observations in astronomy; space plasma and fundamental physics experiments; and lunar resource development. The discovery of a lunar source for propellants may reduce the cost of constructing large permanent facilities in space and enhance other space programs such as Mars exploration. 29 refs.

  1. Virtual Laboratories

    CERN Document Server

    Hut, P


    At the frontier of most areas in science, computer simulations play a central role. The traditional division of natural science into experimental and theoretical investigations is now completely outdated. Instead, theory, simulation, and experimentation form three equally essential aspects, each with its own unique flavor and challenges. Yet, education in computational science is still lagging far behind, and the number of text books in this area is minuscule compared to the many text books on theoretical and experimental science. As a result, many researchers still carry out simulations in a haphazard way, without properly setting up the computational equivalent of a well equipped laboratory. The art of creating such a virtual laboratory, while providing proper extensibility and documentation, is still in its infancy. A new approach is described here, Open Knowledge, as an extension of the notion of Open Source software. Besides open source code, manuals, and primers, an open knowledge project provides simul...

  2. Meeting Report--NASA Radiation Biomarker Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Straume, Tore; Amundson, Sally A,; Blakely, William F.; Burns, Frederic J.; Chen, Allen; Dainiak, Nicholas; Franklin, Stephen; Leary, Julie A.; Loftus, David J.; Morgan, William F.; Pellmar, Terry C.; Stolc, Viktor; Turteltaub, Kenneth W.; Vaughan, Andrew T.; Vijayakumar, Srinivasan; Wyrobek, Andrew J.


    A summary is provided of presentations and discussions from the NASA Radiation Biomarker Workshop held September 27-28, 2007, at NASA Ames Research Center in Mountain View, California. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including for long-duration space travel. Topics discussed include the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage following large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass-spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. Summary conclusions are provided at the end of the report.

  3. Blood-based biomarkers for Parkinson's disease. (United States)

    Chahine, Lama M; Stern, Matthew B; Chen-Plotkin, Alice


    There is a pressing need for biomarkers to diagnose Parkinson's disease (PD), assess disease severity, and prognosticate course. Various types of biologic specimens are potential candidates for identifying biomarkers--defined here as surrogate indicators of physiological or pathophysiological states--but blood has the advantage of being minimally invasive to obtain. There are, however, several challenges to identifying biomarkers in blood. Several candidate biomarkers identified in other diseases or in other types of biological fluids are being pursued as blood-based biomarkers in PD. In addition, unbiased discovery is underway using techniques including metabolomics, proteomics, and gene expression profiling. In this review, we summarize these techniques and discuss the challenges and successes of blood-based biomarker discovery in PD. Blood-based biomarkers that are discussed include α-synuclein, DJ-1, uric acid, epidermal growth factor, apolipoprotein-A1, and peripheral inflammatory markers.

  4. Oral Fluids that Detect Cardiovascular Disease Biomarkers (United States)

    Foley, Joseph D.; Sneed, J. Darrell; Steinhubl, Steven R; Kolasa, Justin; Ebersole, Jeffrey L.; Lin, Yushun; Kryscio, Richard J.; McDevitt, John T.; Campbell, Charles L.; Miller, Craig S.


    Objective To determine the utility of oral fluids for assessment of coronary and cardiovascular (CVD) health. Study Design Twenty-nine patients with pre-existing CVD disease underwent an invasive cardiac procedure (alcohol septal ablation or percutaneous coronary intervention) and provided unstimulated whole saliva (UWS), sublingual swabs (LS), gingival swabs (GS) and serum at 0, 8, 16, 24, 48 hr. Concentrations of 13 relevant biomarkers were determined and correlated with levels in serum and the oral fluids. Results Concentrations of the majority of biomarkers were higher in UWS than LS and GS. Coronary and CVD disease biomarkers in UWS correlated better with serum than LS and GS based on group status and measures of time effect. Seven biomarkers demonstrated time effect changes consistent with serum biomarkers, including C-reactive protein and troponin I. Conclusions Changes in serum biomarker profiles are reflected in oral fluids suggesting that oral fluid biomarkers could aid in the assessment of cardiac ischemia/necrosis. PMID:22769406

  5. Reproductive and developmental toxicity of phthalates. (United States)

    Lyche, Jan L; Gutleb, Arno C; Bergman, Ake; Eriksen, Gunnar S; Murk, AlberTinka J; Ropstad, Erik; Saunders, Margaret; Skaare, Janneche U


    The purposes of this review are to (1) evaluate human and experimental evidence for adverse effects on reproduction and development in humans, produced by exposure to phthalates, and (2) identify knowledge gaps as for future studies. The widespread use of phthalates in consumer products leads to ubiquitous and constant exposure of humans to these chemicals. Phthalates were postulated to produce endocrine-disrupting effects in rodents, where fetal exposure to these compounds was found to induce developmental and reproductive toxicity. The adverse effects observed in rodent models raised concerns as to whether exposure to phthalates represents a potential health risk to humans. At present, di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and butyl benzyl phthalate (BBP) have been demonstrated to produce reproductive and developmental toxicity; thus, this review focuses on these chemicals. For the general population, DEHP exposure is predominantly via food. The average concentrations of phthalates are highest in children and decrease with age. At present, DEHP exposures in the general population appear to be close to the tolerable daily intake (TDI), suggesting that at least some individuals exceed the TDI. In addition, specific high-risk groups exist with internal levels that are several orders of magnitude above average. Urinary metabolites used as biomarkers for the internal levels provide additional means to determine more specifically phthalate exposure levels in both general and high-risk populations. However, exposure data are not consistent and there are indications that secondary metabolites may be more accurate indicators of the internal exposure compared to primary metabolites. The present human toxicity data are not sufficient for evaluating the occurrence of reproductive effects following phthalate exposure in humans, based on existing relevant animal data. This is especially the case for data on female reproductive toxicity, which are

  6. Mechanisms of developmental programming of the metabolic syndrome and related disorders. (United States)

    Luo, Zhong-Cheng; Xiao, Lin; Nuyt, Anne-Monique


    There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, lowered serum high-density lipoprotein cholesterol and impaired glucose tolerance or insulin resistance) and related disorders. This "fetal or developmental origins/programming of disease" concept is now well accepted but the "programming" mechanisms remain poorly understood. We reviewed the major evidence, implications and limitations of current hypotheses in interpreting developmental programming and discuss future research directions. Major current hypotheses to interpret developmental programming include: (1) thrifty phenotype; (2) postnatal accelerated or catch-up growth; (3) glucocorticoid effects; (4) epigenetic changes; (5) oxidative stress; (6) prenatal hypoxia; (7) placental dysfunction; and (8) reduced stem cell number. Some hypothetical mechanisms (2, 4 and 8) could be driven by other upstream "driver" mechanisms. There is a lack of animal studies addressing multiple mechanisms simultaneously and a lack of strong evidence linking clinical outcomes to biomarkers of the proposed programming mechanisms in humans. There are needs for (1) experimental studies addressing multiple hypothetical mechanisms simultaneously; and (2) prospective pregnancy cohort studies linking biomarkers of the proposed mechanisms to clinical outcomes or surrogate biomarker endpoints. A better understanding of the programming mechanisms is a prerequisite for developing early life interventions to arrest the increasing epidemic of the metabolic syndrome, type 2 diabetes and other related disorders.

  7. 77 FR 48995 - Draft National Toxicology Program (NTP) Monograph on Developmental Effects and Pregnancy Outcomes... (United States)


    ... laboratory animals. OHAT has prepared a comprehensive draft NTP Monograph that summarizes the effects on..., placental and breast milk transport, and laboratory animal developmental toxicology for the more frequently... workshops or state- of-the-science evaluations to address issues of importance in environmental...

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

    DEFF Research Database (Denmark)

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


    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...

  9. Troponins Biomarkers Of Miocardic Injury

    Directory of Open Access Journals (Sweden)

    Ana Consuelo González Patiño


    Full Text Available Biomarkers or Biological markers are tools that for their availability, economy, specificity and sensitivity are useful in the diagnosis, prognosis and monitoring of canine and feline patients with cardiovascular alterations; widely used and standardized in human cardiology, presented as an excellent complement, of easy access, for specialized tests such as Doppler ultrasound and electrocardiography that, sometimes, are not available in everyday clinical practice. The cardiac troponins are sensitive and specific biomarkers in the detection of different abnormalities that affect the integrity of the myocardium, these are minimally invasive tests, inexpensive and would provide valuable information in the treatment of cardiac patients; therefore, the possibility of making these part of the protocol in the routine evaluation of patients, with suspect of heart disease should be considered.

  10. Genetic biomarkers in hypertrophic cardiomyopathy. (United States)

    Coats, Caroline J; Elliott, Perry M


    Hypertrophic cardiomyopathy is a common inherited heart muscle disorder associated with sudden cardiac death, arrhythmias and heart failure. Genetic mutations can be identified in approximately 60% of patients; these are commonest in genes that encode proteins of the cardiac sarcomere. Similar to other Mendelian diseases these mutations are characterized by incomplete penetrance and variable clinical expression. Our knowledge of this genetic diversity is rapidly evolving as high-throughput DNA sequencing technology is now used to characterize an individual patient's disease. In addition, the genomic basis of several multisystem diseases associated with a hypertrophic cardiomyopathy phenotype has been elucidated. Genetic biomarkers can be helpful in making an accurate diagnosis and in identifying relatives at risk of developing the condition. In the clinical setting, genetic testing and genetic screening should be used pragmatically with appropriate counseling. Here we review the current role of genetic biomarkers in hypertrophic cardiomyopathy, highlight recent progress in the field and discuss future challenges.

  11. Biomarkers in acute lung injury. (United States)

    Mokra, Daniela; Kosutova, Petra


    Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS.

  12. Glycoscience aids in biomarker discovery

    Directory of Open Access Journals (Sweden)

    Serenus Hua1,2 & Hyun Joo An1,2,*


    Full Text Available The glycome consists of all glycans (or carbohydrates within abiological system, and modulates a wide range of important biologicalactivities, from protein folding to cellular communications.The mining of the glycome for disease markers representsa new paradigm for biomarker discovery; however, this effortis severely complicated by the vast complexity and structuraldiversity of glycans. This review summarizes recent developmentsin analytical technology and methodology as applied tothe fields of glycomics and glycoproteomics. Mass spectrometricstrategies for glycan compositional profiling are described, as arepotential refinements which allow structure-specific profiling.Analytical methods that can discern protein glycosylation at aspecific site of modification are also discussed in detail.Biomarker discovery applications are shown at each level ofanalysis, highlighting the key role that glycoscience can play inhelping scientists understand disease biology.

  13. Candidate immune biomarkers for radioimmunotherapy. (United States)

    Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric


    Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy.

  14. Attentional networks in developmental dyscalculia

    Directory of Open Access Journals (Sweden)

    Henik Avishai


    Full Text Available Abstract Background Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Methods Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test - interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. Results The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. Conclusions These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing.

  15. Introduction of the land snail Eobania vermiculata as a bioindicator organism of terrestrial pollution using a battery of biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Itziou, A., E-mail:; Dimitriadis, V.K., E-mail:


    The present study aimed to enrich the group of sentinel organisms of terrestrial pollution biomonitoring, by investigating the efficacy of the land snail Eobania vermiculata. For this reason, a package of biomarkers was performed on land snails E. vermiculata collected from polluted areas in the field or treated with heavy metals in the laboratory. The biomarkers used were neutral red lysosomal retention assay of the haemocytes, acetylcholinesterase activity in the digestive gland and the haemolymph, and metallothionein content of the digestive gland. Moreover, the morphometric changes in the lysosomal system and the morphometric alterations of the neutral lipids were also investigated. In addition, the content of cadmium, lead and copper was evaluated in the digestive gland of the snails. The results revealed appreciable alterations in the biomarker values both in field- and laboratory-conditions, accompanied by significant correlations among the biomarkers. Therefore, this exploratory study suggests the utility of E. vermiculata as a sentinel organism for biomonitoring the biologic impact of terrestrial pollution, and supports the package's efficacy of the selected biomarkers. - Research Highlights: {yields} Significant changes were noted in the values of the applied biomarkers. {yields} A package of biomarkers is supported to be an efficient tool for biomoniroting studies. {yields} The land snail Eobania vermiculata is proposed to be a good bioindicator organism in terrestrial pollution studies.

  16. [Proteomic biomarkers in Parkinson's disease]. (United States)

    Bandrés, Sara; Durán, Raquel; Barrero, Francisco; Ramírez, Manuel; Vives, Francisco


    Parkinson's disease (PD) is a neurodegenerative disorder that affects movement and is caused by the death of the dopaminergic neurons in the compact part of the substantia nigra. Its diagnosis is essentially clinical, but although the signs and symptoms of PD are well known, the rate of diagnostic error is relatively high. It is estimated that 10-30% of patients initially diagnosed with PD are later reclassified. This disease has a high prevalence beyond the age of 60, and one of its biggest problems is that it is diagnosed when the degenerative process is already at a very advanced stage. Therefore, it is necessary to look for other biomarkers that make it possible to carry out an early diagnosis of PD, follow up its development, distinguish it from other related pathologies (parkinsonisms) and help monitor the effect of novel therapies. The fact that there are mutations that lead to PD, as well as polygenetic combinations that can act as risk factors, suggests the possibility of measuring the proteins resulting from the expression of these genes in peripheral tissues. And once their sensitivity and specificity have been proved they could be used as biomarkers for PD, even in the early phases of the disease. The aim of this work is to focus on a detailed review of the main candidate proteomic biomarkers researched to date by discussing the most recent literature.

  17. Developmental toxicity of cigarette butts - An underdeveloped issue. (United States)

    Lee, Wenjau; Lee, Chih Chun


    Cigarette butts (CBs) littering is not just an unsightly nuisance but also a public health problem, because chemicals contained in cigarettes can leach into aquatic environments and pose a risk to the health of humans and wildlife. However, this risk is largely unrecognized or ignored by the public, and toxicological evidence of CBs is scarce. Therefore, we used medaka embryos (Oryzias latipes) to explore developmental toxicity of CBs. The embryos were exposed to various concentrations of leachates from smoked and unsmoked cigarette tobacco (ST and UST) and filters (SF and USF), and observed from 1 to 3 days post-fertilization. The images were recorded and several developmental endpoints analyzed. The values from these endpoints were then used to calculate the Integrated Biomarker Response and evaluate overall effects of the leachates. Some of the embryos were allowed to hatch, and the hatchlings were tested for anxiety-like behavior. Our results showed that low concentrations of the leachates from ST, UST, and SF raised the heart rate, accelerated development, and changed behavior, while high concentrations lowered the heart rate, suppressed development, and increased mortality. The lowest observed effect concentration for the leachates was ≤0.2piece (pc)/L. The USF leachate had no effect at the concentration of 20pc/L. Developmental toxicity of the leachates was ranked as: ST>UST>SF>USF. This study has demonstrated for the first time that CB leachates affect fish development, and provided toxicological evidence to better assess ecological impacts of CBs.

  18. Dietary biomarkers: advances, limitations and future directions

    Directory of Open Access Journals (Sweden)

    Hedrick Valisa E


    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.

  19. Dietary biomarkers: advances, limitations and future directions. (United States)

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


    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.

  20. Developmental dyslexia and vision

    Directory of Open Access Journals (Sweden)

    Quercia P


    Full Text Available Patrick Quercia,1 Léonard Feiss,2 Carine Michel31Department of Ophthalmology, University Hospital, Dijon, France; 2Office of Ophthalmology, Beaune, France; 3University of Burgundy, Dijon, INSERM U1093, Cognition, Action et Plasticité Sensorimotrice, Dijon, FranceAbstract: Developmental dyslexia affects almost 10% of school-aged children and represents a significant public health problem. Its etiology is unknown. The consistent presence of phonological difficulties combined with an inability to manipulate language sounds and the grapheme–phoneme conversion is widely acknowledged. Numerous scientific studies have also documented the presence of eye movement anomalies and deficits of perception of low contrast, low spatial frequency, and high frequency temporal visual information in dyslexics. Anomalies of visual attention with short visual attention spans have also been demonstrated in a large number of cases. Spatial orientation is also affected in dyslexics who manifest a preference for spatial attention to the right. This asymmetry may be so pronounced that it leads to a veritable neglect of space on the left side. The evaluation of treatments proposed to dyslexics whether speech or oriented towards the visual anomalies remains fragmentary. The advent of new explanatory theories, notably cerebellar, magnocellular, or proprioceptive, is an incentive for ophthalmologists to enter the world of multimodal cognition given the importance of the eye's visual input.Keywords: reading, ocular motility, dyslexia, neglect, spatial representation

  1. Developmental dyslexia and vision. (United States)

    Quercia, Patrick; Feiss, Léonard; Michel, Carine


    Developmental dyslexia affects almost 10% of school-aged children and represents a significant public health problem. Its etiology is unknown. The consistent presence of phonological difficulties combined with an inability to manipulate language sounds and the grapheme-phoneme conversion is widely acknowledged. Numerous scientific studies have also documented the presence of eye movement anomalies and deficits of perception of low contrast, low spatial frequency, and high frequency temporal visual information in dyslexics. Anomalies of visual attention with short visual attention spans have also been demonstrated in a large number of cases. Spatial orientation is also affected in dyslexics who manifest a preference for spatial attention to the right. This asymmetry may be so pronounced that it leads to a veritable neglect of space on the left side. The evaluation of treatments proposed to dyslexics whether speech or oriented towards the visual anomalies remains fragmentary. The advent of new explanatory theories, notably cerebellar, magnocellular, or proprioceptive, is an incentive for ophthalmologists to enter the world of multimodal cognition given the importance of the eye's visual input.

  2. Virtual Laboratories (United States)

    Hut, P.

    At the frontier of most areas in science, computer simulations playa central role. The traditional division of natural science into experimental and theoretical investigations is now completely outdated. Instead, theory, simulation, and experimentation form three equally essential aspects, each with its own unique flavor and challenges. Yet, education in computational science is still lagging far behind, and the number of text books in this area is minuscule compared to the many text books on theoretical and experimental science. As a result, many researchers still carry out simulations in a haphazard way, without properly setting up the computational equivalent of a well equipped laboratory. The art of creating such a virtual laboratory, while providing proper extensibility and documentation, is still in its infancy. A new approach is described here, Open Knowledge, as an extension of the notion of Open Source software. Besides open source code, manuals, and primers, an open knowledge project provides simulated dialogues between code developers, thus sharing not only the code, but also the motivations behind the code.

  3. Digital pathology and image analysis in tissue biomarker research. (United States)

    Hamilton, Peter W; Bankhead, Peter; Wang, Yinhai; Hutchinson, Ryan; Kieran, Declan; McArt, Darragh G; James, Jacqueline; Salto-Tellez, Manuel


    Digital pathology and the adoption of image analysis have grown rapidly in the last few years. This is largely due to the implementation of whole slide scanning, advances in software and computer processing capacity and the increasing importance of tissue-based research for biomarker discovery and stratified medicine. This review sets out the key application areas for digital pathology and image analysis, with a particular focus on research and biomarker discovery. A variety of image analysis applications are reviewed including nuclear morphometry and tissue architecture analysis, but with emphasis on immunohistochemistry and fluorescence analysis of tissue biomarkers. Digital pathology and image analysis have important roles across the drug/companion diagnostic development pipeline including biobanking, molecular pathology, tissue microarray analysis, molecular profiling of tissue and these important developments are reviewed. Underpinning all of these important developments is the need for high quality tissue samples and the impact of pre-analytical variables on tissue research is discussed. This requirement is combined with practical advice on setting up and running a digital pathology laboratory. Finally, we discuss the need to integrate digital image analysis data with epidemiological, clinical and genomic data in order to fully understand the relationship between genotype and phenotype and to drive discovery and the delivery of personalized medicine.

  4. Predictive Modeling of Developmental Toxicity (United States)

    The use of alternative methods in conjunction with traditional in vivo developmental toxicity testing has the potential to (1) reduce cost and increase throughput of testing the chemical universe, (2) prioritize chemicals for further targeted toxicity testing and risk assessment,...

  5. Circulating Biomarkers for Duchenne Muscular Dystrophy (United States)

    Aartsma-Rus, Annemieke; Spitali, Pietro


    Abstract Duchenne muscular dystrophy is the most common form of muscular dystrophy. Genetic and biochemical research over the years has characterized the cause, pathophysiology and development of the disease providing several potential therapeutic targets and/or biomarkers. High throughput – omic technologies have provided a comprehensive understanding of the changes occurring in dystrophic muscles. Murine and canine animal models have been a valuable source to profile muscles and body fluids, thus providing candidate biomarkers that can be evaluated in patients. This review will illustrate known circulating biomarkers that could track disease progression and response to therapy in patients affected by Duchenne muscular dystrophy. We present an overview of the transcriptomic, proteomic, metabolomics and lipidomic biomarkers described in literature. We show how studies in muscle tissue have led to the identification of serum and urine biomarkers and we highlight the importance of evaluating biomarkers as possible surrogate endpoints to facilitate regulatory processes for new medicinal products. PMID:27858763

  6. Molecular biomarkers for grass pollen immunotherapy. (United States)

    Popescu, Florin-Dan


    Grass pollen allergy represents a significant cause of allergic morbidity worldwide. Component-resolved diagnosis biomarkers are increasingly used in allergy practice in order to evaluate the sensitization to grass pollen allergens, allowing the clinician to confirm genuine sensitization to the corresponding allergen plant sources and supporting an accurate prescription of allergy immunotherapy (AIT), an important approach in many regions of the world with great plant biodiversity and/or where pollen seasons may overlap. The search for candidate predictive biomarkers for grass pollen immunotherapy (tolerogenic dendritic cells and regulatory T cells biomarkers, serum blocking antibodies biomarkers, especially functional ones, immune activation and immune tolerance soluble biomarkers and apoptosis biomarkers) opens new opportunities for the early detection of clinical responders for AIT, for the follow-up of these patients and for the development of new allergy vaccines.

  7. Advances in Biomarker Research in Parkinson's Disease. (United States)

    Mehta, Shyamal H; Adler, Charles H


    Parkinson's disease (PD) is the second most common neurodegenerative disease, and the numbers are projected to double in the next two decades with the increase in the aging population. An important focus of current research is to develop interventions to slow the progression of the disease. However, prerequisites to it include the development of reliable biomarkers for early diagnosis which would identify at-risk groups and disease progression. In this review, we present updated evidence of already known clinical biomarkers (such as hyposmia and rapid eye movement (REM) sleep behavior disorder (RBD)) and neuroimaging biomarkers, as well as newer possible markers in the blood, CSF, and other tissues. While several promising candidates and methods to assess these biomarkers are on the horizon, it is becoming increasingly clear that no one candidate will clearly fulfill all the roles as a single biomarker. A multimodal and combinatorial approach to develop a battery of biomarkers will likely be necessary in the future.

  8. Modeling the effects of developmental variation on insect phenology. (United States)

    Yurk, Brian P; Powell, James A


    Phenology, the timing of developmental events such as oviposition or pupation, is highly dependent on temperature; since insects are ectotherms, the time it takes them to complete a life stage (development time) depends on the temperatures they experience. This dependence varies within and between populations due to variation among individuals that is fixed within a life stage (giving rise to what we call persistent variation) and variation from random effects within a life stage (giving rise to what we call random variation). It is important to understand how both types of variation affect phenology if we are to predict the effects of climate change on insect populations.We present three nested phenology models incorporating increasing levels of variation. First, we derive an advection equation to describe the temperature-dependent development of a population with no variation in development time. This model is extended to incorporate persistent variation by introducing a developmental phenotype that varies within a population, yielding a phenotype-dependent advection equation. This is further extended by including a diffusion term describing random variation in a phenotype-dependent Fokker-Planck development equation. These models are also novel because they are formulated in terms of development time rather than developmental rate; development time can be measured directly in the laboratory, whereas developmental rate is calculated by transforming laboratory data. We fit the phenology models to development time data for mountain pine beetles (MPB) (Dendroctonus ponderosae Hopkins [Coleoptera: Scolytidae]) held at constant temperatures in laboratory experiments. The nested models are parameterized using a maximum likelihood approach. The results of the parameterization show that the phenotype-dependent advection model provides the best fit to laboratory data, suggesting that MPB phenology may be adequately described in terms of persistent variation alone. MPB

  9. In vivo evaluation and comparison of developmental toxicity and teratogenicity of perfluoroalkyl compounds using Xenopus embryos. (United States)

    Kim, Miran; Son, Jungeun; Park, Mi Seon; Ji, Yurim; Chae, Soomin; Jun, Changduk; Bae, Jong-Sup; Kwon, Taek Kyu; Choo, Yun-Sik; Yoon, Hosung; Yoon, Duhak; Ryoo, Jaewoong; Kim, Sang-Hyun; Park, Mae-Ja; Lee, Hyun-Shik


    Perfluoroalkyl compounds (PFCs) are environmental toxicants that persistently accumulate in human blood. Their widespread detection and accumulation in the environment raise concerns about whether these chemicals might be developmental toxicants and teratogens in ecosystem. We evaluated and compared the toxicity of PFCs of containing various numbers of carbon atoms (C8-11 carbons) on vertebrate embryogenesis. We assessed the developmental toxicity and teratogenicity of various PFCs. The toxic effects on Xenopus embryos were evaluated using different methods. We measured teratogenic indices (TIs), and investigated the mechanisms underlying developmental toxicity and teratogenicity by measuring the expression of organ-specific biomarkers such as xPTB (liver), Nkx2.5 (heart), and Cyl18 (intestine). All PFCs that we tested were found to be developmental toxicants and teratogens. Their toxic effects were strengthened with increasing length of the fluorinated carbon chain. Furthermore, we produced evidence showing that perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFuDA) are more potent developmental toxicants and teratogens in an animal model compared to the other PFCs we evaluated [perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA)]. In particular, severe defects resulting from PFDA and PFuDA exposure were observed in the liver and heart, respectively, using whole mount in situ hybridization, real-time PCR, pathologic analysis of the heart, and dissection of the liver. Our studies suggest that most PFCs are developmental toxicants and teratogens, however, compounds that have higher numbers of carbons (i.e., PFDA and PFuDA) exert more potent effects.

  10. Developmental changes in hippocampal associative coding. (United States)

    Goldsberry, Mary E; Kim, Jangjin; Freeman, John H


    Behavioral analyses of the ontogeny of memory have shown that hippocampus-dependent learning emerges relatively late in postnatal development compared with simple associative learning. Maturation of hippocampal mnemonic mechanisms has been hypothesized to underlie the development of the later emerging learning processes. However, the role of hippocampal maturation in learning has not been examined directly. The goal of the present study was to examine developmental changes in hippocampal neuronal coding during acquisition of a hippocampus-dependent learning task. We recorded activity from CA1 pyramidal cells in rat pups while they were trained on trace eyeblink conditioning. Trace eyeblink conditioning is a Pavlovian conditioning task that involves the association of a conditioned stimulus (CS) with an unconditioned stimulus over a stimulus-free trace interval. The inclusion of the trace interval is what makes the task hippocampus dependent. In the present study, rats were trained at 21-23, 24-26, and 31-33 d of age. Previous research from our laboratory and others shows that trace conditioning begins to emerge during the third postnatal week. The results indicate that hippocampal neurons show a substantial increase in responsiveness to task-relevant events during development. Moreover, there is an age-related increase in the proportion of neurons that respond to a combination of trial events (e.g., CS and trace). Our findings indicate that the developmental emergence of hippocampally mediated learning is related to increases in the strength and complexity of CA1 associative coding.

  11. Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization. (United States)

    Amur, S; LaVange, L; Zineh, I; Buckman-Garner, S; Woodcock, J


    The discovery, development, and use of biomarkers for a variety of drug development purposes are areas of tremendous interest and need. Biomarkers can become accepted for use through submission of biomarker data during the drug approval process. Another emerging pathway for acceptance of biomarkers is via the biomarker qualification program developed by the Center for Drug Evaluation and Research (CDER, US Food and Drug Administration). Evidentiary standards are needed to develop and evaluate various types of biomarkers for their intended use and multiple stakeholders, including academia, industry, government, and consortia must work together to help develop this evidence. The article describes various types of biomarkers that can be useful in drug development and evidentiary considerations that are important for qualification. A path forward for coordinating efforts to identify and explore needed biomarkers is proposed for consideration.

  12. Laboratory Activities

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Christopher F.; Serne, R. Jeffrey


    This chapter summarizes the laboratory activities performed by PNNL’s Vadose Zone Characterization Project in support of the Tank Farm Vadose Zone Program, led by CH2M HILL Hanford Group, Inc. The results of these studies are contained in numerous reports (Lindenmeier et al. 2002; Serne et al. 2002a, 2002b, 2002c, 2002d, 2002e; Lindenmeier et al. 2003; Serne et al. 2004a, 2004b; Brown et al. 2005, 2006a, 2007; Serne et al. 2007) and have generated much of the data reported in Chapter 22 (Geochemistry-Contaminant Movement), Appendix G (Geochemistry-Contaminant Movement), and Cantrell et al. (2007, SST WMA Geochemistry Data Package – in preparation). Sediment samples and characterization results from PNNL’s Vadose Zone Characterization Project are also shared with other science and technology (S&T) research projects, such as those summarized in Chapter 12 (Associated Science Activities).

  13. Biomarkers of selenium status in dogs


    Van Zelst, Marielle; Hesta, Myriam; Gray, Kerry; Staunton, Ruth; Du Laing, Gijs; Janssens, Geert


    Background: Inadequate dietary selenium (Se) intake in humans and animals can lead to long term health problems, such as cancer. In view of the owner's desire for healthy longevity of companion animals, the impact of dietary Se provision on long term health effects warrants investigation. Little is currently known regards biomarkers, and rate of change of such biomarkers in relation to dietary selenium intake in dogs. In this study, selected biomarkers were assessed for their suitability to d...

  14. Neurophysiological biomarkers for Lewy body dementias


    Cromarty, Ruth A.; Elder, Greg J.; Graziadio, Sara; Baker, Mark; Bonanni, Laura; Onofrj, Marco; O’Brien, John T.; Taylor, John-Paul


    Objective Lewy body dementias (LBD) include both dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD), and the differentiation of LBD from other neurodegenerative dementias can be difficult. Currently, there are few biomarkers which might assist early diagnosis, map onto LBD symptom severity, and provide metrics of treatment response. Traditionally, biomarkers in LBD have focussed on neuroimaging modalities; however, as biomarkers need to be simple, inexpensive and non-...

  15. Developmental attentional dyslexia. (United States)

    Friedmann, Naama; Kerbel, Noa; Shvimer, Lilach


    Attentional dyslexia is a reading deficit in which letters migrate between neighboring words, but are correctly identified and keep their correct relative position within the word. Thus, for example, fig tree can be read as fig free or even tie free. This study reports on 10 Hebrew-speaking individuals with developmental attentional dyslexia and explores in detail the characteristics of their between-word errors. Each participant read 2290 words, presented in word pairs: 845 horizontally presented word pairs, 240 vertically presented word pairs, and 60 nonword pairs. The main results are that almost all migrations preserve the relative position of the migrating letter within the word, indicating that the between-word position can be impaired while the within-word position encoding remains intact. This result is also supported by the finding that the participants did not make many letter position errors within words. Further analyses indicated that more errors occur in longer words, that most migrations occur in final letters (which are the leftmost letters in Hebrew), and that letters migrate both horizontally and vertically, and more frequently from the first to the second word in horizontal presentation. More migrations occurred when the result of migration was an existing word. Similarity between words in a pair did not increase error rates, and more migrations occurred when the words shared fewer letters. The between-word errors included the classic errors of migration of a letter between words, but also omission of one instance of a letter that appeared in the same position in the two words, an error that constituted a considerable percentage of the between-word errors, and intrusion of a letter from one word to the corresponding position in the neighboring word without erasing the original letter in the same position.

  16. Current and future biomarkers in allergic asthma. (United States)

    Zissler, U M; Esser-von Bieren, J; Jakwerth, C A; Chaker, A M; Schmidt-Weber, C B


    Diagnosis early in life, sensitization, asthma endotypes, monitoring of disease and treatment progression are key motivations for the exploration of biomarkers for allergic rhinitis and allergic asthma. The number of genes related to allergic rhinitis and allergic asthma increases steadily; however, prognostic genes have not yet entered clinical application. We hypothesize that the combination of multiple genes may generate biomarkers with prognostic potential. The current review attempts to group more than 161 different potential biomarkers involved in respiratory inflammation to pave the way for future classifiers. The potential biomarkers are categorized into either epithelial or infiltrate-derived or mixed origin, epithelial biomarkers. Furthermore, surface markers were grouped into cell-type-specific categories. The current literature provides multiple biomarkers for potential asthma endotypes that are related to T-cell phenotypes such as Th1, Th2, Th9, Th17, Th22 and Tregs and their lead cytokines. Eosinophilic and neutrophilic asthma endotypes are also classified by epithelium-derived CCL-26 and osteopontin, respectively. There are currently about 20 epithelium-derived biomarkers exclusively derived from epithelium, which are likely to innovate biomarker panels as they are easy to sample. This article systematically reviews and categorizes genes and collects current evidence that may promote these biomarkers to become part of allergic rhinitis or allergic asthma classifiers with high prognostic value.

  17. Biomarkers in Parkinson's disease: a funder's perspective. (United States)

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


    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.

  18. Predictive testing of early CIN behaviour by molecular biomarkers. (United States)

    Baak, Jan P A; Kruse, Arnold-Jan; Janssen, Emiel; van Diermen, Bianca


    Each year, 330,000 new Cervical Intraepithelial Neoplasias(CIN) occur in the European Union (EU) of which 120,000 are early CIN where grade (1, 2) indicates the progression-risk to CIN-3 and therefore determines the treatment choice. However, the Positive Predictive Value (PPV) of CIN grade to predict progression is low (10% and 20% for CIN-1 and -2 respectively, 16% on average) resulting in an enormous number of over-treatments indicating worrisome grade reproducibility.Certain molecular biomarkers such as Ki-67 have a higher PPV (30%, an improvement of 14%), which in Europe alone could improve treatment for many thousands of women per year with considerable cost reduction for the health care system. The quantitative Ki-67 prognostic model has been validated in independent retrospective and prospective studies from different laboratories. Moreover, the PPV of Ki-67 alone can be improved by additional molecular biomarkers (retinoblastoma protein = Rb, cytokeratins= CK-14/-13). Combined Ki67-Rb allows a 2-tiered progression-risk subgroup assignment as very low ( approximately 0% progression, 71% of all CIN-I/II patients)and high risk (48% progression risk, incidence 32%), leaving a small (7% of all) prognostically undetermined group (17% progression). Additional CK-14 and -13 analysis can sub-classify the high-risk in an intermediate and very high risk subgroup(with 40% and 100% progression risks respectively).Thus, molecular biomarkers are potentially important determinators of early CIN lesion behaviour. Important factors for widespread acceptance of molecular biomarkers are (1) market penetration by user-friendly equipment, (2) (inter)national keeping of GLP conditions (reproducibility, independent validation), requiring customer-driven industrial efforts,governmental measures, and additional PPV improvement to further reduce over-treatment.

  19. The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers

    DEFF Research Database (Denmark)

    Mattsson, Niklas; Andreasson, Ulf; Persson, Staffan


    . The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.......The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories...

  20. Bio Engineering Laboratory (United States)

    Federal Laboratory Consortium — Description/History: Chemistry and biology laboratoriesThe Bio Engineering Laboratory (BeL) is theonly full spectrum biotechnology capability within the Department...

  1. Bio Engineering Laboratory (United States)

    Federal Laboratory Consortium — Description/History: Chemistry and biology laboratories The Bio Engineering Laboratory (BeL) is theonly full spectrum biotechnology capability within the Department...


    Federal Laboratory Consortium — This laboratory provides biomechanical and physical analyses for both military and commercial footwear. The laboratory contains equipment that is integral to the us...

  3. Advanced Chemistry Laboratory (United States)

    Federal Laboratory Consortium — Description/History: Chemistry laboratory The Advanced Chemistry Laboratory (ACL) is a unique facility designed for working with the most super toxic compounds known...

  4. Physical Sciences Laboratory (PSL) (United States)

    Federal Laboratory Consortium — PNNL's Physical Sciences Laboratory (PSL) houses 22 research laboratories for conducting a wide-range of research including catalyst formulation, chemical analysis,...

  5. Distributed Energy Technology Laboratory (United States)

    Federal Laboratory Consortium — The Distributed Energy Technologies Laboratory (DETL) is an extension of the power electronics testing capabilities of the Photovoltaic System Evaluation Laboratory...

  6. Urinary peptidomics identifies potential biomarkers for major depressive disorder. (United States)

    Wang, Ying; Chen, Jianjun; Chen, Liang; Zheng, Peng; Xu, Hong-Bo; Lu, Jia; Zhong, Jiaju; Lei, Yang; Zhou, Chanjuan; Ma, Qingwei; Li, Yan; Xie, Peng


    Major depressive disorder (MDD) is a debilitating psychiatric illness with no available objective laboratory-based diagnostic test. In this study, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based peptidomics was applied to identify potential urinary diagnostic biomarkers for MDD. A training set of 42 first-episode drug-naive MDD patients and 28 age- and gender-matched healthy controls (HC) was used to develop a peptide diagnostic pattern. Then, the diagnostic efficacy of this pattern was assessed in an independent blinded test set consisting of 24 MDD patients and 13 age- and gender-matched HC. A combination of five potential biomarkers was identified, yielding a sensitivity of 91.7% and specificity of 84.6% in the test set. Moreover, the protein precursors of four of the five peptides were identified by tandem mass spectrometric analysis: serum albumin, apolipoprotein A-I, protein AMBP, and basement membrane-specific heparan sulfate proteoglycan core protein. Taken together, the peptide pattern may be valuable for establishing an objective laboratory-based diagnostic test for MDD.

  7. Biomarkers of chronic alcohol misuse

    Directory of Open Access Journals (Sweden)

    Gonzalo P


    Full Text Available Philippe Gonzalo,1 Sylvie Radenne,2 Sylvie Gonzalo31Laboratoire de Biochimie, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France; 2Service d'Hépatologie-Gastroentérologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France; 3Laboratoire Biomnis, Lyon, FranceAbstract: Biological markers of chronic alcoholism can be divided into two groups: direct and indirect markers. Direct markers (mainly blood or serum and urine ethanol, ethylglucuronide, ethyl sulfate, and phosphatidylethanol directly track the intake of alcohol and vary in their sensitivity and kinetics of appearance and clearance. Indirect markers (mean corpuscular volume,γ-glutamyl transferase, alanine aminotransferase and aspartate aminotransferase, and carbohydrate-deficient transferrin are biological parameters that are influenced by a steady and significant alcohol intake. We discuss the values of these tests and the relevance of their prescriptions for the clinical evaluation of heavy drinking. We indicate, when known, the pathophysiological mechanism of their elevations. We also discuss the amount and time of alcohol consumption required to give a positive result and the duration of abstinence required for the return to normal values. The forensic use of these biomarkers will not be considered in this review.Keywords: alcoholism, biomarker, CDT, relapse, alcohol-induced liver disease

  8. Biomarkers in Pancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Maria Serafeim Theochari


    Full Text Available The aim of biomarkers is to identify patients most likely to benefit from a therapeutic strategy. Pancreatic neuroendocrinetumors are rare neoplasms that arise in the endocrine tissues of the pancreas. Pancreatic neuroendocrine tumors represent3% of primary pancreatic neoplasms and their incidence has risen. The SMAD4 gene is located on chromosome 18q andsomeday the SMAD4 gene status may be useful for prognostic stratification and therapeutic decision. The cells respond toenvironmental signals by modulating the expressions of genes contained within the nucleus, when genes are activated aretranscribed to generate messenger RNA (mRNA. The examination of multiple expressed genes and proteins provides moreuseful information for prognostication of individual tumors. Here we summarize and discuss findings presented at the 2014ASCO Gastrointestinal Cancers Symposium. Anna Karpathakis et al. (Abstract #212 reported data about the role of DNAmethylation in gastrointestinal neuroendocrine tumors. Christina Lynn Roland et al. (Abstract #250 looked the impact OfSMAD4 on oncologic outcomes. Bong Kynn Kang et al. (Abstract #251 investigated prognostic biomarker using microRNAarray technology.

  9. Cerebrospinal fluid IL-12p40, CXCL13 and IL-8 as a combinatorial biomarker of active intrathecal inflammation.

    Directory of Open Access Journals (Sweden)

    Bibiana Bielekova

    Full Text Available Diagnosis and management of the neuroinflammatory diseases of the central nervous system (CNS are hindered by the lack of reliable biomarkers of active intrathecal inflammation. We hypothesized that measuring several putative inflammatory biomarkers simultaneously will augment specificity and sensitivity of the biomarker to the clinically useful range. Based on our pilot experiment in which we measured 18 inflammatory biomarkers in 10-fold concentrated cerebrospinal fluid (CSF derived from 16 untreated patients with highly active multiple sclerosis (MS we selected a combination of three CSF biomarkers, IL-12p40, CXCL13 and IL-8, for further validation.Concentrations of IL-12p40, CXCL13 and IL-8 were determined in a blinded fashion in CSF samples from an initial cohort (n = 72 and a confirmatory cohort (n = 167 of prospectively collected, untreated subjects presenting for a diagnostic work-up of possible neuroimmunological disorder. Diagnostic conclusion was based on a thorough clinical workup, which included laboratory assessment of the blood and CSF, neuroimaging and longitudinal follow-up. Receiver operating characteristic (ROC curve analysis in conjunction with principal component analysis (PCA, which was used to combine information from all three biomarkers, assessed the diagnostic value of measured biomarkers.Each of the three biomarkers was significantly increased in MS and other inflammatory neurological disease (OIND in comparison to non-inflammatory neurological disorder patients (NIND at least in one cohort. However, considering all three biomarkers together improved accuracy of predicting the presence of intrathecal inflammation to the consistently good to excellent range (area under the ROC curve = 0.868-0.924.Future clinical studies will determine if a combinatorial biomarker consisting of CSF IL-12p40, CXCL13 and IL-8 provides utility in determining the presence of active intrathecal inflammation in diagnostically

  10. Biomarker Genes for Detecting Estrogenic Activity of Endocrine Disruptors via Estrogen Receptors

    Directory of Open Access Journals (Sweden)

    Hyun Yang


    Full Text Available Endocrine disruptors (EDs are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by binding to these receptors. EDs are therefore a global concern and assays should be developed to efficiently determine whether these compounds are detrimental to biological systems. Diverse experimental methods may help determine the endocrine disrupting potential of EDs and evaluate the adverse effects of a single and/or combination of these reagents. Currently, biomarkers have been employed to objectively measure EDs potency and understand the underlying mechanisms. Further studies are required to develop ideal screening methods and biomarkers to determine EDs potency at environmentally relevant concentrations. In this review, we describe the biomarkers for estrogenicity of EDs identified both in vitro and in vivo, and introduce a biomarker, cabindin-D9k (CaBP-9k, that may be used to assess estrogenic activity of EDs.

  11. Biomarker genes for detecting estrogenic activity of endocrine disruptors via estrogen receptors. (United States)

    Jung, Eui-Man; An, Beum-Soo; Yang, Hyun; Choi, Kyung-Chul; Jeung, Eui-Bae


    Endocrine disruptors (EDs) are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by binding to these receptors. EDs are therefore a global concern and assays should be developed to efficiently determine whether these compounds are detrimental to biological systems. Diverse experimental methods may help determine the endocrine disrupting potential of EDs and evaluate the adverse effects of a single and/or combination of these reagents. Currently, biomarkers have been employed to objectively measure EDs potency and understand the underlying mechanisms. Further studies are required to develop ideal screening methods and biomarkers to determine EDs potency at environmentally relevant concentrations. In this review, we describe the biomarkers for estrogenicity of EDs identified both in vitro and in vivo, and introduce a biomarker, cabindin-D(9k) (CaBP-9k), that may be used to assess estrogenic activity of EDs.

  12. Exploration of new HCC biomarkers

    Directory of Open Access Journals (Sweden)

    Regina M. Santella


    Full Text Available

    Analysis of plasma/serum for levels of viral antigens or antibodies to viral proteins has been used extensively as an early biomarker of potential risk of HCC. In addition, detection of elevated levels of alpha-fetoprotein is commonly used for early identification of HCC. Unfortunately, both of these approaches are not highly sensitive or specific. As a result, there is continuing investigation to identify additional biomarkers that may help in the early identification of cases. The use of DNA isolated from plasma or serum for detection of gene specific methylation has been discussed previously. In addition, tumor DNA isolated from blood has been analyzed for the presence of p53 mutations and found in a subset of cases to be present years prior to diagnosis as for methylated DNA. The general level of DNA present in blood has also been suggested as a potential biomarker of cancer.

    Among the newer methods being tested are the detection of specific mutations in HBV. In many cases of HCC in China and Africa a double mutation, an A to T transversion at nucleotide 1762 and a G to A transition at nucleotide 1764 (1762T/1764A have been found. These mutations have been associated with increased severity of HBV infection and cirrhosis suggesting that they might be a useful biomarker for high risk subjects.

    The field of proteomics also holds promise for the development of new biomarkers. A number of groups are developing mass spectrometry methods for the identification of serum/plasma proteomic patterns that will distinguish bloods of HCC cases from those of controls. While some interesting preliminary data have been developed for several cancers, much additional work needs to be done in this area

  13. Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: Influence of Gestation Length and Timing of Neonatal Examinations on Litter Data in Controls (United States)

    Laboratories conducting developmental and reproductive toxicity studies with rodents use varied protocols for determining the timing of neonatal litter examinations and subsequent measurements. Most laboratories determine timing based on the day of birth (DOB); l.e., gestation le...

  14. Cytokines as Biomarkers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Agata Burska


    Full Text Available RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge’s relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.

  15. Proteomic Biomarkers for Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana


    This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

  16. Bias in emerging biomarkers for bipolar disorder

    DEFF Research Database (Denmark)

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


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

  17. DNA Methylation Biomarkers: Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Thomas Mikeska


    Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

  18. Biomarkers in Alzheimer’s disease

    Institute of Scientific and Technical Information of China (English)

    Rajka M Liscic; Yuanhan Yang


    Alzheimer’s disease (AD) so far did not have promising treatment. The accurate and early diagnosis is still the important issue. For these purpose, biomarkers related to diagnosis, clinical course, and other aims have been proposed and reported. Meanwhile, along with the ongoing researches for AD, biomarkers with their own aims are also on the way.

  19. Cytokines as biomarkers in rheumatoid arthritis. (United States)

    Burska, Agata; Boissinot, Marjorie; Ponchel, Frederique


    RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria) and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge's relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.

  20. Consensus on biomarkers for neuroendocrine tumour disease (United States)

    Oberg, Kjell; Modlin, Irvin M; De Herder, Wouter; Pavel, Marianne; Klimstra, David; Frilling, Andrea; Metz, David C; Heaney, Anthony; Kwekkeboom, Dik; Strosberg, Jonathan; Meyer, Timothy; Moss, Steven F; Washington, Kay; Wolin, Edward; Liu, Eric; Goldenring, James


    Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours. PMID:26370353

  1. Current and emerging biomarkers of hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Yang X


    Full Text Available Xi Yang, William F Salminen, Laura K SchnackenbergDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USAAbstract: Drug-induced liver injury (DILI is of great concern to human health. Generally, liver function and injury is evaluated based upon clinical signs, a select group of serum clinical biomarkers, and occasionally liver biopsies. While alanine aminotransferase, the most commonly used biomarker of hepatocellular injury, is a sensitive marker of liver injury, it is not necessarily specific for liver injury. Furthermore, alanine aminotransferase levels may not always correlate with the extent of injury. Therefore, new hepatotoxicity biomarkers are needed that are more predictive and specific indicators of liver injury and altered function. In addition, no current biomarker provides prognostic information about ultimate outcome once injury occurs, and any new biomarker filling this need is desperately needed. The omics technologies, including genomics, proteomics, and metabolomics, are being used in preclinical animal studies as well as clinical studies to evaluate markers of hepatotoxicity in easily obtained biofluids, such as urine and serum. Recently, the evaluation of circulating microRNAs in urine and blood has also shown promise for the identification of novel, sensitive markers of liver injury. This review evaluates the current status of proposed biomarkers of hepatotoxicity from the omics platforms, as well as from analysis of microRNAs. A brief description of the qualification of proposed biomarkers is also given.Keywords: biomarkers, hepatotoxicity, metabolomics, microRNA, proteomics, transcriptomics

  2. Milk fat biomarkers and cardiometabolic disease (United States)

    Risérus, Ulf; Marklund, Matti


    Purpose of review Dairy is a major food group with potential impact on cardiometabolic health. Self-reported dairy intake has limitations that can partly be avoided by using biomarkers. This review aims to summarize the evidence of odd-chain saturated fatty acids (OCFAs), that is, pentadecanoic acid (C15 : 0) and heptadecanoic acid (17 : 0), as biomarkers of dairy fat intake. In addition, the associations of OCFA biomarkers with cardiometabolic disease will be overviewed. Recent findings Adipose tissue 15 : 0 is the preferred biomarker but also circulating 15 : 0, and to a weaker extent 17 : 0, reflects both habitual and changes in dairy intake. Whereas results from studies assessing cardiovascular outcomes are inconsistent, OCFA biomarkers are overall associated with lower diabetes risk. Residual confounding should however be considered until interventional data and mechanisms are available. Although OCFA biomarkers mainly reflect dairy fat intake, recently proposed endogenous synthesis and metabolism do motivate further research. Summary Taking into account the study population diet and limitations of OCFA biomarkers, both adipose and circulating levels of 15 : 0, in particular, are useful for estimating total dairy fat intake. OCFA biomarkers are overall not linked to cardiovascular disease risk, but a possible beneficial role of dairy foods in diabetes prevention warrant further study. PMID:27906713

  3. Theme: Laboratory Facilities Improvement. (United States)

    Miller, Glen M.; And Others


    Includes "Laboratory Facilities Improvement" (Miller); "Remodeling Laboratories for Agriscience Instruction" (Newman, Johnson); "Planning for Change" (Mulcahy); "Laboratory Facilities Improvement for Technology Transfer" (Harper); "Facilities for Agriscience Instruction" (Agnew et al.); "Laboratory Facility Improvement" (Boren, Dwyer); and…

  4. Novel diagnostic biomarkers for prostate cancer

    Directory of Open Access Journals (Sweden)

    Chikezie O. Madu, Yi Lu


    Full Text Available Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of

  5. Novel diagnostic biomarkers for prostate cancer. (United States)

    Madu, Chikezie O; Lu, Yi


    Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The

  6. Diagnostic and prognostic epigenetic biomarkers in cancer. (United States)

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


    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.

  7. Cellular Proteases as Cancer Biomarkers: A Review

    Directory of Open Access Journals (Sweden)

    Sarah R. Röthlisberger


    Full Text Available Over the past few decades a variety of biomolecules have been proposed as diagnostic biomarkers and predictors of severity for transmissible and nontransmissible diseases. Studies in a range of cancers have revealed many biomarkers with great potential in cancer diagnosis, in establishing tumor stage, progression, and response to therapies; such as the Kallikrein and Metalloproteinase families. Traditionally blood (serum and tissue have been the main biological sources of biomarker discovery, but in the past decade urine has emerged as a promising source of cancer biomarkers. In this review we will focus on two large families, the Kallikrein family of serine proteases discovered in serum, and the Metalloproteinase family of zinc proteases discovered in urine, as potential cancer biomarkers.

  8. Diagnostic and Prognostic Biomarkers in Melanoma (United States)

    Leininger, Jennifer; Hamby, Carl; Safai, Bijan


    Melanoma is a lethal melanocytic neoplasm. Unfortunately, the histological diagnosis can be difficult at times. Distinguishing ambiguous melanocytic neoplasms that are benign nevi from those that represent true melanoma is important both for treatment and prognosis. Diagnostic biomarkers currently used to assist in the diagnosis of melanoma are usually specific only for melanocytic neoplasms and not necessarily for their ability to metastasize. Traditional prognostic biomarkers include depth of invasion and mitotic count. Newer diagnostic and prognostic biomarkers utilize immunohistochemical staining as well as ribonucleic acid, micro-ribonucleic acid, and deoxyribonucleic acid assays and fluorescence in situ hybridization. Improved diagnostic and prognostic biomarkers are of increasing importance in the treatment of melanoma with the development of newer and more targeted therapies. Herein, the authors review many of the common as well as newer diagnostic and prognostic biomarkers used in melanoma. PMID:25013535

  9. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy


    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

  10. Novel Biomarkers of Abdominal Aortic Aneurysm Disease: Identifying Gaps and Dispelling Misperceptions

    Directory of Open Access Journals (Sweden)

    Demetrios Moris


    Full Text Available Abdominal aortic aneurysm (AAA is a prevalent and potentially life-threatening disease. Early detection by screening programs and subsequent surveillance has been shown to be effective at reducing the risk of mortality due to aneurysm rupture. The aim of this review is to summarize the developments in the literature concerning the latest biomarkers (from 2008 to date and their potential screening and therapeutic values. Our search included human studies in English and found numerous novel biomarkers under research, which were categorized in 6 groups. Most of these studies are either experimental or hampered by their low numbers of patients. We concluded that currently no specific laboratory markers allow screeing for the disease and monitoring its progression or the results of treatment. Further studies and studies in larger patient groups are required in order to validate biomarkers as cost-effective tools in the AAA disease.

  11. Biomarkers and sustainable innovation in cardiovascular drug development: lessons from near and far afield. (United States)

    Medford, Russell M; Dagi, T Forcht; Rosenson, Robert S; Offermann, Margaret K


    Future innovative therapies targeting cardiovascular disease (CVD) have the potential to improve health outcomes and to contain rising healthcare costs. Unsustainable increases in the size, cost and duration of clinical trial programs necessary for regulatory approval, however, threaten the entire innovation enterprise. Rising costs for clinical trials are due in large part to increasing demands for hard cardiovascular clinical endpoints as measures of therapeutic efficacy. The development and validation of predictive and surrogate biomarkers, as laboratory or other objective measures predictive or reflective of clinical endpoints, are an important part of the solution to this challenge. This review will discuss insights applicable to CVD derived from the use of predictive biomarkers in oncologic drug development, the evolving role of high density lipoprotein (HDL) in CVD drug development and the impact biomarkers and surrogates have on the continued investment from multiple societal sources critical for innovative CVD drug discovery and development.

  12. The renaissance of developmental biology. (United States)

    St Johnston, Daniel


    Since its heyday in the 1980s and 90s, the field of developmental biology has gone into decline; in part because it has been eclipsed by the rise of genomics and stem cell biology, and in part because it has seemed less pertinent in an era with so much focus on translational impact. In this essay, I argue that recent progress in genome-wide analyses and stem cell research, coupled with technological advances in imaging and genome editing, have created the conditions for the renaissance of a new wave of developmental biology with greater translational relevance.

  13. Urinary biomarkers of smokers' exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach. (United States)

    Gregg, Evan O; Minet, Emmanuel; McEwan, Michael


    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.

  14. Biomarkers in Parkinson's disease (recent update). (United States)

    Sharma, Sushil; Moon, Carolyn Seungyoun; Khogali, Azza; Haidous, Ali; Chabenne, Anthony; Ojo, Comfort; Jelebinkov, Miriana; Kurdi, Yousef; Ebadi, Manuchair


    Parkinson's disease (PD) is the second most common neurodegenerative disorder mostly affecting the aging population over sixty. Cardinal symptoms including, tremors, muscle rigidity, drooping posture, drooling, walking difficulty, and autonomic symptoms appear when a significant number of nigrostriatal dopaminergic neurons are already destroyed. Hence we need early, sensitive, specific, and economical peripheral and/or central biomarker(s) for the differential diagnosis, prognosis, and treatment of PD. These can be classified as clinical, biochemical, genetic, proteomic, and neuroimaging biomarkers. Novel discoveries of genetic as well as nongenetic biomarkers may be utilized for the personalized treatment of PD during preclinical (premotor) and clinical (motor) stages. Premotor biomarkers including hyper-echogenicity of substantia nigra, olfactory and autonomic dysfunction, depression, hyposmia, deafness, REM sleep disorder, and impulsive behavior may be noticed during preclinical stage. Neuroimaging biomarkers (PET, SPECT, MRI), and neuropsychological deficits can facilitate differential diagnosis. Single-cell profiling of dopaminergic neurons has identified pyridoxal kinase and lysosomal ATPase as biomarker genes for PD prognosis. Promising biomarkers include: fluid biomarkers, neuromelanin antibodies, pathological forms of α-Syn, DJ-1, amyloid β and tau in the CSF, patterns of gene expression, metabolomics, urate, as well as protein profiling in the blood and CSF samples. Reduced brain regional N-acetyl-aspartate is a biomarker for the in vivo assessment of neuronal loss using magnetic resonance spectroscopy and T2 relaxation time with MRI. To confirm PD diagnosis, the PET biomarkers include [(18)F]-DOPA for estimating dopaminergic neurotransmission, [(18)F]dG for mitochondrial bioenergetics, [(18)F]BMS for mitochondrial complex-1, [(11)C](R)-PK11195 for microglial activation, SPECT imaging with (123)Iflupane and βCIT for dopamine transporter, and urinary

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

    Directory of Open Access Journals (Sweden)

    Brian Dean


    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.

  16. Dissecting the Syndrome of Schizophrenia: Progress toward Clinically Useful Biomarkers. (United States)

    Dean, Brian


    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.

  17. Biomarkers in canine parvovirus enteritis. (United States)

    Schoeman, J P; Goddard, A; Leisewitz, A L


    Canine parvovirus (CPV) enteritis has, since its emergence in 1978, remained a common and important cause of morbidity and mortality in young dogs. The continued incidence of parvoviral enteritis is partly due to the virus' capability to evolve into more virulent and resistant variants with significant local gastrointestinal and systemic inflammatory sequelae. This paper reviews current knowledge on historical-, signalment-, and clinical factors as well as several haematological-, biochemical- and endocrine parameters that can be used as diagnostic and prognostic biomarkers in CPV enteritis. These factors include season of presentation, purebred nature, bodyweight, vomiting, leukopaenia, lymphopaenia, thrombocytopaenia, hypercoagulability, hypercortisolaemia, hypothyroxinaemia, hypoalbuminaemia, elevated C-reactive protein and tumour necrosis factor, hypocholesterolaemia and hypocitrullinaemia. Factors contributing to the manifestations of CPV infection are multiple with elements of host, pathogen, secondary infections, underlying stressors and environment affecting severity and outcome. The availability of several prognosticators has made identification of patients at high risk of death and their subsequent targeted management more rewarding.

  18. Cheating by exploitation of developmental prestalk patterning in Dictyostelium discoideum.

    Directory of Open Access Journals (Sweden)

    Anupama Khare


    Full Text Available The cooperative developmental system of the social amoeba Dictyostelium discoideum is susceptible to exploitation by cheaters-strains that make more than their fair share of spores in chimerae. Laboratory screens in Dictyostelium have shown that the genetic potential for facultative cheating is high, and field surveys have shown that cheaters are abundant in nature, but the cheating mechanisms are largely unknown. Here we describe cheater C (chtC, a strong facultative cheater mutant that cheats by affecting prestalk differentiation. The chtC gene is developmentally regulated and its mRNA becomes stalk-enriched at the end of development. chtC mutants are defective in maintaining the prestalk cell fate as some of their prestalk cells transdifferentiate into prespore cells, but that defect does not affect gross developmental morphology or sporulation efficiency. In chimerae between wild-type and chtC mutant cells, the wild-type cells preferentially give rise to prestalk cells, and the chtC mutants increase their representation in the spore mass. Mixing chtC mutants with other cell-type proportioning mutants revealed that the cheating is directly related to the prestalk-differentiation propensity of the victim. These findings illustrate that a cheater can victimize cooperative strains by exploiting an established developmental pathway.

  19. Biomarkers in chronic adult hydrocephalus

    Directory of Open Access Journals (Sweden)

    Kitchen Neil D


    Full Text Available Abstract Awareness of the importance of chronic adult hydrocephalus has been raised again with the recent emergence of epidemiological studies. It is estimated that between 5 and 10% of patients suffering from dementia might, in fact, have chronic hydrocephalus. Although, surgical diversion of the cerebrospinal fluid (CSF represents the only known procedure able to treat the symptoms of this condition, the selection of surgical patients has always been problematic. In the last 40 years, we have become wiser in using appropriate diagnostic tests for the selection of these patients; however, the area of biological markers has so far been overlooked in this condition, in contrast to that for other neurodegenerative disorders and dementias. Biomarkers are biological substances that may be used to indicate either the onset or the presence, and the progression of a clinical condition, being closely linked to its pathophysiology. In such a setting they might assist in the more appropriate selection of patients for shunt surgery. In this article, we have reviewed research carried out in the last 25 years regarding the identification of serum and CSF biomarkers for chronic hydrocephalus, discussed the potential for each one, and finally discussed the limitations for use, as well as future directions and possibilities in this field. It is concluded that tumour-necrosis factor, tau protein, lactate, sulfatide and neurofilament triple protein are the most promising CSF markers for chronic hydrocephalus. At present however, none of these meet the criteria required to justify a change clinical practice. In the future, collaborative multi-centre projects will be needed to obtain more substantial data that overcome the problems that arise from small individual and uncoordinated studies.

  20. Early Stage Health Technology Assessment for Precision Biomarkers in Oral Health and Systems Medicine. (United States)

    Steuten, Lotte M G


    Health technology assessment (HTA) is a crucial science that influences the responsible and evidence-based transition of new discoveries from laboratory to applications in the clinic and society. HTA has recently moved "upstream" so as to assess technologies from their onset at their discovery, design, or planning phase. Biomarker research is relatively recent in oral health, but growing rapidly with investments made to advance dentistry and oral health and importantly, to build effective bridges between oral health and systems medicine since what happens in oral health affects systems pathophysiology, and vice versa. This article offers a synthesis of the latest trends and approaches in early phase HTA, with a view to near future applications in oral health, systems medicine, and biomarker-guided precision medicine. In brief, this review underscores that demonstrating health outcomes of biomarkers and next-generation diagnostics is particularly challenging because they do not always influence long-term outcomes directly, but rather impact subsequent care processes. Biomarker testing costs are typically less of a barrier to uptake in practice than the biomarker's impact on longer term health outcomes. As a single biomarker or next-generation diagnostic in oral health can inform decisions about numerous downstream diagnosis-treatment combinations, early stage "upstream" HTA is crucial in prioritizing the most valuable diagnostic applications to pursue first. For the vast array of oral health biomarkers currently developed, early HTA is necessary to timely and iteratively assess their comparative effectiveness and anticipate the inevitable questions about value for money from regulators and payers.

  1. Linking biomarkers to reproductive success of caged fathead minnows in streams with increasing urbanization (United States)

    Crago, J.; Corsi, S.R.; Weber, D.; Bannerman, R.; Klaper, R.


    Reproductive and oxidative stress biomarkers have been recommended as tools to assess the health of aquatic organisms. Though validated in the laboratory, there are few studies that tie a change in gene expression to adverse reproductive or population outcomes in the field. This paper looked at 17 streams with varying degrees of urbanization to assess the use of biomarkers associated with reproduction or stress in predicting reproductive success of fathead minnows. In addition, the relationship between biomarkers and water quality measures in streams with varying degrees of urbanization was examined. Liver vitellogenin mRNA was correlated with reproduction within a period of 11. d prior to sampling irrespective of habitat, but its correlation with egg output declined at 12. d and beyond indicating its usefulness as a short-term biomarker but its limits as a biomarker of total reproductive output. Stress biomarkers such as glutathione S-transferase may be better correlated with factors affecting reproduction over a longer term. There was a significant correlation between GST mRNA and a variety of anthropogenic pollutants. There was also an inverse correlation between glutathione S-transferase and the amount of the watershed designated as wetland. Egg production over the 21-d was negatively correlated with the amount of urbanization and positively correlated to wetland habitats. This study supports the development of multiple biomarkers linking oxidative stress and other non-reproductive endpoints to changes in aquatic habitats will be useful for predicting the health of fish populations and identifying the environmental factors that may need mitigation for sustainable population management. ?? 2010 Elsevier Ltd.

  2. Predicting Clinical Outcomes Using Molecular Biomarkers. (United States)

    Burke, Harry B


    Over the past 20 years, there has been an exponential increase in the number of biomarkers. At the last count, there were 768,259 papers indexed in directly related to biomarkers. Although many of these papers claim to report clinically useful molecular biomarkers, embarrassingly few are currently in clinical use. It is suggested that a failure to properly understand, clinically assess, and utilize molecular biomarkers has prevented their widespread adoption in treatment, in comparative benefit analyses, and their integration into individualized patient outcome predictions for clinical decision-making and therapy. A straightforward, general approach to understanding how to predict clinical outcomes using risk, diagnostic, and prognostic molecular biomarkers is presented. In the future, molecular biomarkers will drive advances in risk, diagnosis, and prognosis, they will be the targets of powerful molecular therapies, and they will individualize and optimize therapy. Furthermore, clinical predictions based on molecular biomarkers will be displayed on the clinician's screen during the physician-patient interaction, they will be an integral part of physician-patient-shared decision-making, and they will improve clinical care and patient outcomes.

  3. Cerebrospinal Fluid Biomarkers for the Diagnosis of Alzheimer Disease in South Korea (United States)

    Chae, Won Seok; Kim, Hyeong Jun; Shin, Ho Sik; Kim, Saeromi; Im, Ji Young; Ahn, Sang Il; Min, Kyoung Dae; Yim, Soo Jae; Ye, Byoung Seok; Seo, Sang Won; Jeong, Jee Hyang; Park, Kyung Won; Choi, Seong Hye; Na, Duk L.


    Laboratory-specific reference values for cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers are necessary. Our objective was to apply well-known CSF biomarkers and redetermine their diagnostic cutoff values for AD in South Korea. CSF samples from matched control subjects (n=71), patients with AD dementia (ADD, n=76), and other neurological disorders with cognitive decline (OND, n=47) were obtained from 6 Korean dementia clinics according to a standardized protocol. CSF biomarker concentrations were measured using enzyme-linked immunosorbent assay. CSF biomarkers differed significantly between the ADD and control groups (P<0.001 for all), and between the ADD and OND groups (P<0.001 for all). The areas under the curve in differentiation of ADD from control subjects were 0.97 for Aβ42, 0.93 for total tau (tTau), 0.86 for pTau, and 0.99 for both tTau/Aβ42 and pTau/Aβ42 ratios. Our revised cutoff value for Aβ42 was higher than our previous one, whereas the values for the Tau proteins were similar. The tTau/Aβ42 ratio had the highest accuracy, 97%. Our findings highlight the usefulness of CSF AD biomarkers in South Korea, and the necessity of continually testing the reliability of cutoff values. PMID:28030437

  4. Thymidylate Synthase as a Predictive Biomarker for Pemetrexed Response in NSCLC

    Directory of Open Access Journals (Sweden)

    Ali A. Bukhari


    Full Text Available In recent years, major strides in cancer research have made it possible to select personalized chemotherapy recommendations based on an individual patient’s tumor biology. The prognostic and/or predictive ability of biomarkers seeks to tailor the use of targeted chemotherapy and can result in improved clinical outcomes with reduced toxicity. A proliferation of new technology and pharmacotherapeutics in the setting of current FDA Clinical Laboratory Improvement Amendment (CLIA standards has resulted in a recent surge in direct-to-physician biomarker tests. However, in the absence of clinical validation, there is the concern that the biomarkers may be utilized prematurely, resulting in improper chemotherapy selection and patient harm. Thymidylate synthase (TS has been marketed as a predictive biomarker for the use of pemetrexed in NSCLC. We will examine the evidence behind the use of TS as a predictive biomarker to predict response to pemetrexed in NSCLC. At this time, the evidence does not currently support using TS assays to guide chemotherapy selection outside of a clinical research protocol.

  5. Linking Biological and Cognitive Aging: Toward Improving Characterizations of Developmental Time (United States)

    DeCarlo, Correne A.; Dixon, Roger A.


    Objectives. Chronological age is the most frequently employed predictor in life-span developmental research, despite repeated assertions that it is best conceived as a proxy for true mechanistic changes that influence cognition across time. The present investigation explores the potential that selected functional biomarkers may contribute to the more effective conceptual and operational definitions of developmental time. Methods. We used data from the Victoria Longitudinal Study to explore both static and dynamic biological or physiological markers that arguably influence process-specific mechanisms underlying cognitive changes in late life. Multilevel models were fit to test the dynamic coupling between change in theoretically relevant biomarkers (e.g., grip strength, pulmonary function) and change in select cognitive measures (e.g., executive function, episodic and semantic memory). Results. Results showed that, independent of the passage of developmental time (indexed as years in study), significant time-varying covariation was observed linking corresponding declines for select cognitive outcomes and biological markers. Discussion. Our findings support the interpretation that cognitive decline is not due to chronological aging per se but rather reflects multiple causal factors from a broad range of biological and physical health domains that operate along the age continuum. PMID:21743053

  6. The Developmental Psychopathology of Worry (United States)

    Kertz, Sarah J.; Woodruff-Borden, Janet


    Although childhood generalized anxiety disorder is generally understudied, worry, the cardinal feature of GAD, appears to be relatively common in youth. Despite its prevalence, there are few conceptual models of the development of clinical worry in children. The current review provides a framework for integrating the developmental psychopathology…

  7. Early Writing: A Developmental Approach. (United States)

    Goetz, Elizabeth; And Others

    This document consists of four papers on the acquisition of writing skills by young children. The first paper provides a historical and developmental perspective on early writing. Children's development of manual dexterity is briefly overviewed and aspects of the educational approaches of Pestalozzi, Montessori, Chomsky, Rogers and Ashton-Warner…

  8. Topographical ability in Developmental Prosopagnosia

    DEFF Research Database (Denmark)

    Klargaard, Solja; Starrfelt, Randi; Petersen, Anders


    Anecdotal evidence suggests a relation between impaired spatial (navigational) processing and developmental prosopagnosia (DP). To address this formally, we tested nine individuals with DP and 18 matched controls on a four-choice match-to-sample test of (concurrent) topographical perception and t...

  9. Developmental trends in adaptive memory. (United States)

    Otgaar, Henry; Howe, Mark L; Smeets, Tom; Garner, Sarah R


    Recent studies have revealed that memory is enhanced when information is processed for fitness-related purposes. The main objective of the current experiments was to test developmental trends in the evolutionary foundation of memory using different types of stimuli and paradigms. In Experiment 1, 11-year-olds and adults were presented with neutral, negative, and survival-related DRM word lists. We found a memory benefit for the survival-related words and showed that false memories were more likely to be elicited for the survival-related word lists than for the other lists. Experiment 2 examined developmental trends in the survival processing paradigm using neutral, negative, and survival-related pictures. A survival processing advantage was found for survival-related pictures in adults, for negative pictures in 11/12-year-olds, and for neutral pictures in 7/8-year-olds. In Experiment 3, 11/12-year-olds and adults had to imagine the standard survival scenario or an adapted survival condition (or pleasantness condition) that was designed to reduce the possibilities for elaborative processing. We found superior memory retention for both survival scenarios in children and adults. Collectively, our results evidently show that the survival processing advantage is developmentally invariant and that certain proximate mechanisms (elaboration and distinctiveness) underlie these developmental trends.

  10. Person Constancy within Developmental Change. (United States)

    Maccoby, Eleanor E.

    Using findings on the unstability of previously stable physical activity levels of young children as a kind of case study to aid thought about the trait-dimensional approach to developmental continuity and discontinuity, this discussion explores the applicability of a dual theory of concept formation to the problem of personal stability and…

  11. Art/Dance Developmental Chart. (United States)

    Kinda, Crystal L., Comp.; Hand, Leslie, Comp.

    A developmental chart of dance and art is presented according to Piaget's three stages of mental development: intuitive thought, concrete operations, and formal operations. Development is charted for dance/movement and art beginning with a sensorimotor unit (1 to 3 years), through self awareness (3 to 5 years), motor skills (5 to 7 years), form (7…

  12. Developmental Principles: Fact or Fiction

    Directory of Open Access Journals (Sweden)

    A. J. Durston


    Full Text Available While still at school, most of us are deeply impressed by the underlying principles that so beautifully explain why the chemical elements are ordered as they are in the periodic table, and may wonder, with the theoretician Brian Goodwin, “whether there might be equally powerful principles that account for the awe-inspiring diversity of body forms in the living realm”. We have considered the arguments for developmental principles, conclude that they do exist and have specifically identified features that may generate principles associated with Hox patterning of the main body axis in bilaterian metazoa in general and in the vertebrates in particular. We wonder whether this exercise serves any purpose. The features we discuss were already known to us as parts of developmental mechanisms and defining developmental principles (how, and at which level? adds no insight. We also see little profit in the proposal by Goodwin that there are principles outside the emerging genetic mechanisms that need to be taken into account. The emerging developmental genetic hierarchies already reveal a wealth of interesting phenomena, whatever we choose to call them.

  13. Advances in developmental prosopagnosia research. (United States)

    Susilo, Tirta; Duchaine, Bradley


    Developmental prosopagnosia (DP) refers to face recognition deficits in the absence of brain damage. DP affects ∼2% of the population, and it often runs in families. DP studies have made considerable progress in identifying the cognitive and neural characteristics of the disorder. A key challenge is to develop a valid taxonomy of DP that will facilitate many aspects of research.

  14. Vygotsky's Developmental and Educational Psychology (United States)

    Langford, Peter E.


    Vygotsky is widely considered one of the most significant and influential psychologists of the twentieth century. Nevertheless, true appreciation of his theories has been hindered by a lack of understanding of the background to his thought. "Vygotsky's Developmental and Educational Psychology" aims to demonstrate how we can come to a new and…

  15. Developmental dyscalculia: a dysconnection syndrome? (United States)

    Kucian, Karin; Ashkenazi, Simone Schwizer; Hänggi, Jürgen; Rotzer, Stephanie; Jäncke, Lutz; Martin, Ernst; von Aster, Michael


    Numerical understanding is important for everyday life. For children with developmental dyscalculia (DD), numbers and magnitudes present profound problems which are thought to be based upon neuronal impairments of key regions for numerical understanding. The aim of the present study was to investigate possible differences in white matter fibre integrity between children with DD and controls using diffusion tensor imaging. White matter integrity and behavioural measures were evaluated in 15 children with developmental dyscalculia aged around 10 years and 15 matched controls. The main finding, obtained by a whole brain group comparison, revealed reduced fractional anisotropy in the superior longitudinal fasciculus in children with developmental dyscalculia. In addition, a region of interest analysis exhibited prominent deficits in fibres of the superior longitudinal fasciculus adjacent to the intraparietal sulcus, which is thought to be the core region for number processing. To conclude, our results outline deficient fibre projection between parietal, temporal and frontal regions in children with developmental dyscalculia, and therefore raise the question of whether dyscalculia can be seen as a dysconnection syndrome. Since the superior longitudinal fasciculus is involved in the integration and control of distributed brain processes, the present results highlight the importance of considering broader domain-general mechanisms in the diagnosis and therapy of dyscalculia.

  16. Writing Stages: A Developmental Hierarchy. (United States)

    Milner, Joseph O.

    The developmental stages of writing can be related to Jean Piaget's final three stages of development (preoperational, concrete operational, and formal operational) and to the narrative, descriptive, explanative, analytical, and artistic rhetorical modes. As the child enters kindergarten or the first grade, narrative blooms. By this age most young…

  17. Developmental control of cell division

    NARCIS (Netherlands)

    Boxem, M. (Mike)


    During development of multicellular organisms, cell divisions need to be coordinated with the developmental program of the entire organism. Although the mechanisms that drive cells through the division cycle are well understood, very little is known about the pathways that link extracellular signals

  18. Overview: developmental toxicology: new directions. (United States)

    Shuey, Dana; Kim, James H


    Since regulatory agencies began implementing the use of standardized developmental toxicology protocols in the mid-1960s, our knowledge base of embryo-fetal development and technologies for experimentation has grown exponentially. These developmental toxicology protocols were a direct result of the thalidomide tragedy from earlier that decade, when large numbers of women were exposed to the drug and over 10,000 cases of phocomelia resulted. In preventing a recurrence of such tragedies, the testing protocols are immensely successful and the field of toxicology has been dedicated to using them to advance safety and risk assessment of chemicals and pharmaceuticals. Recently, our perspectives on toxicity testing have been challenged by a growing awareness that while we have excelled in hazard identification, we are in dire need of improved methodologies for human health risk assessment, particularly with respect to the large numbers of environmental chemicals for which we have little toxicology data and to the growing sentiment that better alternatives to whole animals tests are needed. To provide a forum for scientists, researchers, and regulators, the Developmental and Reproductive Toxicology Technical Committee of the Health and Environmental Sciences Institute organized a 2-day workshop titled "Developmental Toxicology-New Directions" to evaluate lessons learned over the past 30 years and discuss the future of toxicology testing. The following four articles describe different presentations and discussions that were held over the course of those 2 days.

  19. Developmental Dyscalculia and Medical Assessment. (United States)

    Shalev, Ruth S.; Gross-Tsur, Varda


    Medical evaluation of seven third-grade children with developmental dyscalculia in a mainstream setting identified neurological conditions (including petit mal seizures, Gerstmann syndrome, and attention deficit disorder without hyperactivity) in all the children. Findings suggest that children who are not improving academically should undergo…

  20. Developmental transitions: So what's new?

    NARCIS (Netherlands)

    van der Maas, H.L.J.; Hopkins, B.


    Structural approaches to development, such as Piaget's stage theory, have proved to be problematic in dealing with developmental transitions. More promising in this respect are models of qualitative change that address macroscopical phase shifts in non-linear dynamicalsystems that arise from quantit

  1. Causal Inference and Developmental Psychology (United States)

    Foster, E. Michael


    Causal inference is of central importance to developmental psychology. Many key questions in the field revolve around improving the lives of children and their families. These include identifying risk factors that if manipulated in some way would foster child development. Such a task inherently involves causal inference: One wants to know whether…

  2. Biomarkers in DILI: one more step forward

    Directory of Open Access Journals (Sweden)

    Mercedes Robles-Díaz


    Full Text Available Despite being relatively rare, drug-induced liver injury (DILI is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in omics technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (for example metabolites, proteins or DNA simultaneously enables the identification of ‘toxicity signatures’, which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review we summarize recent advances in the area of DILI biomarker studies.

  3. Biomarkers in Alzheimer's Disease-Recent Update. (United States)

    Sharma, Sushil; Lipincott, Walter


    Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized by loss of memory and cognitive function. It is the common cause of dementia in elderly and is a global health concern as the population of people aged 85 and older, is growing alarmingly. Although pharmacotherapy for the treatment of AD has improved, lot of work remains to treat this devastating disease. AD pathology begins even before the onset of clinical symptoms. Because therapies could be more effective if implemented early in the disease progression, it is highly prudent to discover reliable biomarkers, to detect its exact pathophysiology during pre-symptomatic stage. Biomarker(s) with high sensitivity and specificity would facilitate AD diagnosis at early stages. Currently, CSF amyloid β 1-42, total tau, and phosphorylated tau181 are used as AD biomarkers. This report describes conventional and potential in-vitro and in-vivo biomarkers of AD. Particularly, in-vitro transcriptomic, proteomic, lipidomic, and metabolomic; body fluid biomarkers (C-reactive proteins, homocysteine, α-sunuclein index, and dehydroepiandrosterone sulphate) from blood, serum, plasma, CSF, and saliva; and neuronal, platelets, and lymphocyte microRNA, mtDNA, and Charnoly body are detected. In-vivo physiological and neurobehavioral biomarkers are evaluated by analyzing computerized EEG, event-related potentials, circadian rhythm, and multimodality fusion imaging including: CT, MRI, SPECT, and PET. More specifically, PET imaging biomarkers representing reduced fronto-temporal 18FdG uptake, increased 11C or 18F-PIB uptake, 11C-PBR28 to measure 18 kDa translocator protein (TSPO), a biomarker for inflammation; and 3-D MRI (ventriculomegaly)/MRS are performed for early and effective clinical management of AD.

  4. Biomarkers in DILI: One More Step Forward (United States)

    Robles-Díaz, Mercedes; Medina-Caliz, Inmaculada; Stephens, Camilla; Andrade, Raúl J.; Lucena, M. Isabel


    Despite being relatively rare, drug-induced liver injury (DILI) is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings, and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis, and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in “omics” technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (e.g., metabolites, proteins, or DNA) simultaneously enables the identification of ‘toxicity signatures,’ which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review, we summarize recent advances in the area of DILI biomarker studies. PMID:27597831

  5. Cardiac Biomarkers and Cycling Race

    Directory of Open Access Journals (Sweden)

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier


    Full Text Available In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011, but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac biomarkers: creatin kinase (CK, creating kinase midbrain (CK-MB, myoglobin (MYO, highly sensitive troponin T (hs-TnT and N-terminal brain natriuretic peptide (NT-proBNP. The population studied was a group of young trained cyclists participating in a 177-km cycling race. The group of individuals was selected for maximal homogeneity. Their annual training volume was between 10,000 and 16,000 kilometers. The rhythm of races is comparable and averages 35 km/h, depending on the race’s difficulty. The cardiac frequency was recorded via a heart rate monitor. Three blood tests were taken. The first blood test, T0, was taken approximately 2 hours before the start of the race and was intended to gather values which would act as references for the following tests. The second blood test, T1, was realized within 5 minutes of their arrival. The third and final blood test, T3, was taken 3 hours following their arrival. The CK, CK-MB, MYO, hs-TnT and NT-proBNP were measured on the Roche Diagnostic modular E (Manhein, Germany. For the statistical analysis, an ANOVA and post hoc test of Scheffé were calculated with the Statistica Software version 9.1. We noticed an important significant variation in the cardiac frequency between T0 and T1 (p < 0.0001, T0 and T3 (p < 0.0001, and T1 and T3 (p < 0.01. Table 1 shows the results obtained for the different biomarkers. CK and CK-MB showed significant variation between T0-T1 and T0-T3 (p < 0.0001. Myoglobin increased significantly

  6. Administration on Intellectual and Developmental Disabilities (United States)

    ... Us Home > Programs & Activities > Administration on Disabilities > AIDD Administration on Intellectual and Developmental Disabilities (AIDD) Realizing the ... AIDD has a new address and phone number: Administration for Intellectual and Developmental Disabilities, Administration for Community ...

  7. Mural granulosa cell gene expression associated with oocyte developmental competence

    Directory of Open Access Journals (Sweden)

    Jiang Jin-Yi


    the developmental competence of oocytes. This finding suggests that the most differentially expressed gene, lysyl oxidase, may be a candidate biomarker of oocyte health and useful for the selection of good quality oocytes for assisted reproduction.

  8. Developmental Education Repeaters: Stories about Repetition (United States)

    O'Dell, Jade J.


    Developmental education students make up almost half of the community college population in the United States (Bettinger & Long, 2005). Approximately 42% of first-time freshmen at community colleges must enroll in at least one developmental education course in English, reading and/or math (NCES, 2010). Many developmental education students are…

  9. Werner's Relevance for Contemporary Developmental Psychology. (United States)

    Glick, Joseph A.


    Considers the contributions of Heinz Werner to developmental psychology and identifies the tensions between Werner's theory and the practices of contemporary developmental psychology. Core issues of Werner's psychology concern: (1) development as heuristic, rather than phenomenon; (2) developmental process analysis; and (3) conceptions of the…

  10. The potential use of porphyrins as nondestructive biomarker of contaminant exposure in bird populations; L`uso delle porfirine come biomarker non distruttivo di esposizione in popolazioni aviarie

    Energy Technology Data Exchange (ETDEWEB)

    Casini, S.; Fossi, M.C. [Siena, Univ. (Italy). Dip. Biologia Ambientale


    In this work the potential use of porphyrins as nondestructive biomarker of contaminant exposure in bird populations was investigated. Three laboratory experiments were carried out using Japanese quails (Coturnix coturnix japonica) treated with PCBs, methylmercury, hexachlorobenzene and lead (porphyrins were measured in liver and excreta). For the field validation of this approach two studies were carried out on excreta of colonial and fish eating birds. Porphyrins are confirmed to be suitable biomarkers of PCBs, MeHg and HCB exposure in birds, having also shown for the first two a response-dose relationship and a correlation between destructive and nondestructive samples. [Italiano] In questo lavoro viene proposto l`uso delle porfirie come biomarker non distruttivo di esposizione a contaminanti ambientali in popolazioni di uccelli. Lo studio si e` articolato in tre esperimenti di laboratorio su quaglie gaipponesi (Coturnix coturnix japonica) trattate con PCBs, metilmercurio (MeHg), esaclorobenzene (HCB) e piombo (alle quali stato misurato il contenuto porfirinico nel fegato e negli excreta) e in due campionamenti di excreta in popolazioni di uccelli marini coloniali. Le porfirine si sono confermate buoni biomarkers di esposizione ai contaminanti analizzati, inoltre nelle quaglie trattate con PCBs e MeHg le porfirine hanno subto un accumulo dose-dipendente ed stata misurata una correlazione ytra l`accumulo nel fegato e negli excreta.

  11. Can Biomarkers Help to Diagnose Early Heart Failure with Preserved Ejection Fraction?

    Directory of Open Access Journals (Sweden)

    Jaroslav Meluzín


    Full Text Available Early heart failure with preserved ejection fraction (HFpEF is a frequent disease, but its diagnosis is difficult and relies mostly on the evidence of left ventricular filling pressure (LVFP elevation during exercise. Several reports have suggested that natriuretic peptides plasma levels reflect exercise-induced increase in LVFP, but they still have significant limitations. In this context, any new laboratory biomarker that can accurately reflect LVFP elevation during exercise is desirable. Recently, cardiotrophin-1, soluble endoglin, ST2, growth differentiation factor 15, galectin-3, and other new laboratory markers associated with LVFP have emerged. However, the current data on the relationship of these biomarkers and diastolic dysfunction are limited to resting conditions. Therefore, their secretion deserves to be tested under the exercise to determine their potential role in making a diagnosis of early HFpEF.

  12. Quantitative imaging as cancer biomarker (United States)

    Mankoff, David A.


    The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine

  13. Development of biomarkers for Huntington's disease. (United States)

    Weir, David W; Sturrock, Aaron; Leavitt, Blair R


    Huntington's disease is an autosomal dominant, progressive neurodegenerative disorder, for which there is no disease-modifying treatment. By use of predictive genetic testing, it is possible to identify individuals who carry the gene defect before the onset of symptoms, providing a window of opportunity for intervention aimed at preventing or delaying disease onset. However, without robust and practical measures of disease progression (ie, biomarkers), the efficacy of therapeutic interventions in this premanifest Huntington's disease population cannot be readily assessed. Current progress in the development of biomarkers might enable evaluation of disease progression in individuals at the premanifest stage of the disease; these biomarkers could be useful in defining endpoints in clinical trials in this population. Clinical, cognitive, neuroimaging, and biochemical biomarkers are being investigated for their potential in clinical use and their value in the development of future treatments for patients with Huntington's disease.

  14. Statistical design and evaluation of biomarker studies. (United States)

    Dobbin, Kevin K


    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.

  15. Biomarker monitoring in sports doping control. (United States)

    Pottgiesser, Torben; Schumacher, Yorck Olaf


    Biomarker monitoring can be considered a new era in the effort against doping. Opposed to the old concept in doping control of direct detection of a prohibited substance in a biological sample such as urine or blood, the new paradigm allows a personalized longitudinal monitoring of biomarkers that indicate non-physiological responses independently of the used doping technique or substance, and may cause sanctioning of illicit practices. This review presents the development of biomarker monitoring in sports doping control and focuses on the implementation of the Athlete Biological Passport as the current concept of the World Anti Doping Agency for the detection of blood doping (hematological module). The scope of the article extends to the description of novel biomarkers and future concepts of application.

  16. The development and applications of biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Normandy, J.; Peeters, J. [eds.


    This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community.

  17. Early-Phase Studies of Biomarkers

    DEFF Research Database (Denmark)

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


    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...

  18. Clinical Relevance of Biomarkers of Oxidative Stress

    DEFF Research Database (Denmark)

    Frijhoff, Jeroen; Winyard, Paul G; Zarkovic, Neven;


    SIGNIFICANCE: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino...... acids. RECENT ADVANCES: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES: The literature is very heterogeneous....... It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured...

  19. Biomarkers in Multiple Sclerosis: Role of Antibodies


    Thomas Berger; Markus Reindl


    The first international workshop on “Biomarkers in Multiple Sclerosis” was organized by B. Bielekova, R. Hohlfeld, R. Martin and U. Utz from April 14–16, 2004, in Washington, DC. The workshop intended to discuss the current status and potential applicability of biological markers for the understanding of the pathogenesis, diagnosis, and therapy of multiple sclerosis. The present review summarizes the presentation on the potential role of antibodies as biomarkers for diagnosis, disease activit...

  20. Early Stage Health Technology Assessment for Precision Biomarkers in Oral Health and Systems Medicine


    Steuten, Lotte M.G.


    Health technology assessment (HTA) is a crucial science that influences the responsible and evidence-based transition of new discoveries from laboratory to applications in the clinic and society. HTA has recently moved “upstream” so as to assess technologies from their onset at their discovery, design, or planning phase. Biomarker research is relatively recent in oral health, but growing rapidly with investments made to advance dentistry and oral health and importantly, to build effective bri...

  1. Transferring Cut-off Values between Assays for Cerebrospinal Fluid Alzheimer's Disease Biomarkers


    Garcia Barrado, Leandro; Coart, Els; Vanderstichele, Hugo M. J.; Burzykowski, Tomasz


    Current technologies quantifying cerebrospinal fluid biomarkers to identify subjects with Alzheimer's disease pathology report different concentrations in function of technology and suffer from between-laboratory variability. Hence, lab- and technology-specific cut-off values are required. It is common practice to establish cut-off values on small datasets and, in the absence of well-characterized samples, to transfer the cut-offs to another assay format using 'side-by-side' testing of sample...

  2. Aberrant Crypt Foci: The Case for Inclusion as a Biomarker for Colon Cancer


    Jay Morris; Michael J. Wargovich; Brown, Vondina R.


    Aberrant crypt foci (ACF) are one of the earliest histopathological manifestations of colon cancer. In this review, we critically present the molecular, cellular, histopathological, and chemopreventive evidence that ACF are relevant biomarkers for colon cancer. The laboratory and clinical evidence are highly suggestive that ACF are in the pathway leading to colon cancer, but not all ACF will do so. The possible fate and outcome of ACF in the progression toward colon cancer may be dependent on...

  3. Advanced Chemistry Laboratory (United States)

    Federal Laboratory Consortium — Description/History: Chemistry laboratoryThe Advanced Chemistry Laboratory (ACL) is a unique facility designed for working with the most super toxic compounds known...

  4. Gun Dynamics Laboratory (United States)

    Federal Laboratory Consortium — The Gun Dynamics Laboratory is a research multi-task facility, which includes two firing bays, a high bay area and a second floor laboratory space. The high bay area...

  5. NASA Space Radiation Laboratory (United States)

    Federal Laboratory Consortium — The NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory is a NASA funded facility, delivering heavy ion beams to a target area where scientists...

  6. Lincoln Laboratory Grid (United States)

    Federal Laboratory Consortium — The Lincoln Laboratory Grid (LLGrid) is an interactive, on-demand parallel computing system that uses a large computing cluster to enable Laboratory researchers to...

  7. Denver District Laboratory (DEN) (United States)

    Federal Laboratory Consortium — Program CapabilitiesDEN-DO Laboratory is a multi-functional laboratory capable of analyzing most chemical analytes and pathogenic/non-pathogenic microorganisms found...

  8. 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

  9. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael


    Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

  10. Blood biomarker for Parkinson disease: peptoids (United States)

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


    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

  11. Biomarker-based dissection of neurodegenerative diseases. (United States)

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


    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.

  12. The use of biomarkers in clinical osteoporosis. (United States)

    Cabral, Hebert Wilson Santos; Andolphi, Bruna Ferreira Galone; Ferreira, Brunna Vila Coutinho; Alves, Danielle Cristina Filgueira; Morelato, Renato Lírio; Chambo, Antônio; Borges, Lizânia Spinassé


    Osteoporosis is a disease of ascending character in the world population; in this context, bone biomarkers are being increasingly studied in order to aid in the diagnosis and monitoring of these patients. The main objective of this study was a literature review of articles whose main theme was the use of biomarkers for bone formation and degradation, and to evaluate their possible applicability in clinical practice. Literature review was performed through articles indexed and published in the last five years in the PubMed database. The findings of this study showed that most of the previously selected articles were published in the last two years, and the most cited markers were bone resorption, C-terminal collagen telopeptide (CTX), showing the highest correlation with the dynamics of bone, and the biomarker of bone formation, bone-specific alkaline phosphatase (BAP), which is increased in the event of fracture or may suggest another bone disease. There was an increase in published articles, associating different bone biomarkers and their clinical applicability, especially for treatment control. Our findings suggest that in recent years there has been significant increase in publications evaluating the use of bone turnover biomarkers for bone formation and resorption and their possible clinical applicability, especially in the monitoring of treatment. Still, we believe that further studies need to be conducted to confirm these findings, given the advantages that bone biomarkers can deliver in the clinical management of the disease.

  13. An Integrated Protein Chemistry Laboratory: Chlorophyll and Chlorophyllase (United States)

    Arkus, Kiani A. J.; Jez, Joseph M.


    Chlorophyll, the most abundant pigment in nature, is degraded during normal plant growth, when leaves change color, and at specific developmental stages. Chlorophyllase catalyzes the first chemical reaction in this process, that is, the hydrolysis of chlorophyll into chlorophyllide. Here, we describe a series of laboratory sessions designed to…

  14. Multichannel waveguides for the simultaneous detection of disease biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Mukundan, Harshini [Los Alamos National Laboratory; Price, Dominique Z [Los Alamos National Laboratory; Grace, Wynne K [Los Alamos National Laboratory; Swanson, Basil I [Los Alamos National Laboratory


    The sensor team at the Los Alamos National Laboratory has developed a waveguide-based optical biosensor that has previously been used for the detection of biomarkers associated with diseases such as tuberculosis, breast cancer, anthrax and influenza in complex biological samples (e.g., serum and urine). However, no single biomarker can accurately predict disease. To address this issue, we developed a multiplex assay for the detection of components of the Bacillus anthracis lethal toxin on single mode planar optical waveguides with tunable quantum dots as the fluorescence reporter. This limited ability to multiplex is still insufficient for accurate detection of disease or for monitoring prognosis. In this manuscript, we demonstrate for the first time, the design, fabrication and successful evaluation of a multichannel planar optical waveguide for the simultaneous detection of at least three unknown samples in quadruplicate. We demonstrate the simultaneous, rapid (30 min), quantitative (with internal standard) and sensitive (limit of detection of 1 pM) detection of protective antigen and lethal factor of Bacillus anthracis in complex biological samples (serum) using specific monoclonal antibodies labeled with quantum dots as the fluorescence reporter.

  15. [Cerebrospinal fluid biomarkers for the early diagnosis of Parkinson's disease]. (United States)

    da Costa, Andreia Gomes; Gago, Miguel Fernandes; Garrett, Carolina


    In current medical practice, the diagnosis of Parkinson's disease remains essentially clinical. This practice determines that the diagnosis of Parkinson's disease is done in an already advanced neuropathological stage of the disease. The aim of this study is to review the validity of cerebrospinal fluid protein biological markers in the early diagnosis of Parkinson's disease. The a-synuclein and DJ-1 proteins, due to their role in the hereditary Parkinson's disease, have been the most widely studied cerebrospinal biomarkers. Nevertheless, they have had divergent results mostly owing to different processing, identification and control of laboratory techniques. The new proteomic techniques, directed to the detection of multiple undifferentiated proteins in cerebrospinal fluid (eg. ceruloplasmin, chromogranin B, apoH), are promising. The early diagnosis of Parkinson's disease is imperious as it is a progressive neurodegenerative disorder that causes extensive morbidity. Most of current scientific research in Parkinson's disease is focused on the discovery of neuroprotective drugs. Thus, the definition of biomarkers for the early diagnosis of Parkinson's disease is highly relevant.

  16. Laboratory-acquired brucellosis

    DEFF Research Database (Denmark)

    Fabiansen, C.; Knudsen, J.D.; Lebech, A.M.


    Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9......Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9...

  17. Developmental assessment of Spanish grammar. (United States)

    Toronto, A S


    The Developmental Assessment of Spanish Grammar (DASG) provides a language analysis procedure for Spanish-speaking children similar to the Developmental Sentence Scoring (DSS) procedure in English. The DASG is not an attempted translation of the DSS but was developed independently, taking into consideration the present knowledge of Spanish language acquisition. The purpose of the DASG is to evaluate the language of children with deficient grammatical skills in Spanish and to serve as a model for structuring Spanish language therapy. Proposed syntactic hierarchies for the following six grammatical categories are presented: indefinite pronouns and noun modifiers, personal pronouns, primary verbs, secondary verbs, conjunctions, and interrogative words. Weighted scores are assigned to groups of structures within the hierarchies and are used to score Spanish sentences children use spontaneously in conversation with an adult. The DASG was standardized on 128 Spanish-speaking children between the ages of 3.0 and 6.11 years. Norms and reliability measures are presented.

  18. Developmental insights into mature cognition. (United States)

    Keil, Frank C


    Three cases are described that illustrate new ways in which developmental research is informing the study of cognition in adults: statistical learning, neural substrates of cognition, and extended concepts. Developmental research has made clear the ubiquity of statistical learning while also revealing is limitations as a stand-alone way to acquire knowledge. With respect to neural substrates, development has uncovered links between executive processing and fronto-striatal circuits while also pointing to many aspects of high-level cognition that may not be neatly reducible to coherent neural descriptions. For extended concepts, children have made especially clear the weaknesses of intuitive theories in both children and adults while also illustrating other cognitive capacities that are used at all ages to navigate the socially distributed aspects of knowledge.

  19. Developmental Dynamics of Rett Syndrome. (United States)

    Feldman, Danielle; Banerjee, Abhishek; Sur, Mriganka


    Rett Syndrome was long considered to be simply a disorder of postnatal development, with phenotypes that manifest only late in development and into adulthood. A variety of recent evidence demonstrates that the phenotypes of Rett Syndrome are present at the earliest stages of brain development, including developmental stages that define neurogenesis, migration, and patterning in addition to stages of synaptic and circuit development and plasticity. These phenotypes arise from the pleotropic effects of MeCP2, which is expressed very early in neuronal progenitors and continues to be expressed into adulthood. The effects of MeCP2 are mediated by diverse signaling, transcriptional, and epigenetic mechanisms. Attempts to reverse the effects of Rett Syndrome need to take into account the developmental dynamics and temporal impact of MeCP2 loss.

  20. Fuels Processing Laboratory (United States)

    Federal Laboratory Consortium — NETL’s Fuels Processing Laboratory in Morgantown, WV, provides researchers with the equipment they need to thoroughly explore the catalytic issues associated with...

  1. Photovoltaic Characterization Laboratory (United States)

    Federal Laboratory Consortium — NIST's PV characterization laboratory is used to measure the electrical performance and opto-electronic properties of solar cells and modules. This facility consists...

  2. Embedded Processor Laboratory (United States)

    Federal Laboratory Consortium — The Embedded Processor Laboratory provides the means to design, develop, fabricate, and test embedded computers for missile guidance electronics systems in support...

  3. Rapid Prototyping Laboratory (United States)

    Federal Laboratory Consortium — The ARDEC Rapid Prototyping (RP) Laboratory was established in December 1992 to provide low cost RP capabilities to the ARDEC engineering community. The Stratasys,...

  4. Coatings and Corrosion Laboratory (United States)

    Federal Laboratory Consortium — Purpose: The mission of the Coatings and Corrosion Laboratory is to develop and analyze the effectiveness of innovative coatings test procedures while evaluating the...

  5. Geospatial Services Laboratory (United States)

    Federal Laboratory Consortium — FUNCTION: To process, store, and disseminate geospatial data to the Department of Defense and other Federal agencies. DESCRIPTION: The Geospatial Services Laboratory...

  6. Neural Systems Laboratory (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  7. Thermogravimetric Analysis Laboratory (United States)

    Federal Laboratory Consortium — At NETL’s Thermogravimetric Analysis Laboratory in Morgantown, WV, researchers study how chemical looping combustion (CLC) can be applied to fossil energy systems....


    Federal Laboratory Consortium — This laboratory contains equipment that performs a broad array of microbiological analyses for pathogenic and spoilage microorganisms. It performs challenge studies...

  9. Environmental Microbiology Laboratory (United States)

    Federal Laboratory Consortium — The Environmental Microbiology Laboratory, located in Bldg. 644 provides a dual-gas respirometer for measurement of oxygen consumption and carbon dioxide evolution...

  10. Laboratory of Chemical Physics (United States)

    Federal Laboratory Consortium — Current research in the Laboratory of Chemical Physics is primarily concerned with experimental, theoretical, and computational problems in the structure, dynamics,...

  11. Research Combustion Laboratory (RCL) (United States)

    Federal Laboratory Consortium — The Research Combustion Laboratory (RCL) develops aerospace propulsion technology by performing tests on propulsion components and materials. Altitudes up to 137,000...


    Federal Laboratory Consortium — This laboratory conducts basic and applied human research studies to characterize cognitive performance as influenced by militarily-relevant contextual and physical...

  13. Acoustic Technology Laboratory (United States)

    Federal Laboratory Consortium — This laboratory contains an electro-magnetic worldwide data collection and field measurement capability in the area of acoustic technology. Outfitted by NASA Langley...

  14. Tactical Systems Integration Laboratory (United States)

    Federal Laboratory Consortium — The Tactical Systems Integration Laboratory is used to design and integrate computer hardware and software and related electronic subsystems for tactical vehicles....

  15. Combustion Research Laboratory (United States)

    Federal Laboratory Consortium — The Combustion Research Laboratory facilitates the development of new combustion systems or improves the operation of existing systems to meet the Army's mission for...

  16. Sandia National Laboratories (United States)

    Federal Laboratory Consortium — For more than 60 years, Sandia has delivered essential science and technology to resolve the nation's most challenging security issues.Sandia National Laboratories...

  17. Wind Structural Testing Laboratory (United States)

    Federal Laboratory Consortium — This facility provides office space for industry researchers, experimental laboratories, computer facilities for analytical work, and space for assembling components...

  18. Vehicle Development Laboratory (United States)

    Federal Laboratory Consortium — FUNCTION: Supports the development of prototype deployment platform vehicles for offboard countermeasure systems. DESCRIPTION: The Vehicle Development Laboratory is...

  19. Central Laboratories Services (United States)

    Federal Laboratory Consortium — The TVA Central Laboratories Services is a comprehensive technical support center, offering you a complete range of scientific, engineering, and technical services....

  20. Wireless Emulation Laboratory (United States)

    Federal Laboratory Consortium — The Wireless Emulation Laboratory (WEL) is a researchtest bed used to investigate fundamental issues in networkscience. It is a research infrastructure that emulates...

  1. Space Weather Laboratory (United States)

    Federal Laboratory Consortium — The Space Weather Computational Laboratory is a Unix and PC based modeling and simulation facility devoted to research analysis of naturally occurring electrically...

  2. Composites Characterization Laboratory (United States)

    Federal Laboratory Consortium — The purpose of the Composites Characterization Laboratory is to investigate new and/or modified matrix materials and fibers for advanced composite applications both...

  3. Vehicle Development Laboratory (United States)

    Federal Laboratory Consortium — FUNCTION: Supports the development of prototype deployment platform vehicles for offboard countermeasure systems.DESCRIPTION: The Vehicle Development Laboratory is...

  4. Engineered Natural Systems Laboratory (United States)

    Federal Laboratory Consortium — With its pressure vessels that simulate the pressures and temperatures found deep underground, NETL’s Engineered Natural Systems Laboratory in Pittsburgh, PA, gives...

  5. Virtual Training Devices Laboratory (United States)

    Federal Laboratory Consortium — The Virtual Training Devices (VTD) Laboratory at the Life Cycle Software Engineering Center, Picatinny Arsenal, provides a software testing and support environment...

  6. Advanced Manufacturing Laboratory (United States)

    Federal Laboratory Consortium — The Advanced Manufacturing Laboratory at the University of Maryland provides the state of the art facilities for realizing next generation products and educating the...

  7. Intelligent Optics Laboratory (United States)

    Federal Laboratory Consortium — The Intelligent Optics Laboratory supports sophisticated investigations on adaptive and nonlinear optics; advancedimaging and image processing; ground-to-ground and...

  8. Semiconductor Laser Measurements Laboratory (United States)

    Federal Laboratory Consortium — The Semiconductor Laser Measurements Laboratory is equipped to investigate and characterize the lasing properties of semiconductor diode lasers. Lasing features such...

  9. Optical Remote Sensing Laboratory (United States)

    Federal Laboratory Consortium — The Optical Remote Sensing Laboratory deploys rugged, cutting-edge electro-optical instrumentation for the collection of various event signatures, with expertise in...


    Federal Laboratory Consortium — This laboratory develops screening assays, tests and modifies biosensor equipment, and optimizes food safety testing protocols for the military and civilian sector...

  11. Atmospheric Measurements Laboratory (AML) (United States)

    Federal Laboratory Consortium — The Atmospheric Measurements Laboratory (AML) is one of the nation's leading research facilities for understanding aerosols, clouds, and their interactions. The AML...

  12. Translating discovery in zebrafish pancreatic development to human pancreatic cancer: biomarkers, targets, pathogenesis, and therapeutics. (United States)

    Yee, Nelson S; Kazi, Abid A; Yee, Rosemary K


    Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer.

  13. Developmental transcriptome of Aplysia californica'

    KAUST Repository

    Heyland, Andreas


    Genome-wide transcriptional changes in development provide important insight into mechanisms underlying growth, differentiation, and patterning. However, such large-scale developmental studies have been limited to a few representatives of Ecdysozoans and Chordates. Here, we characterize transcriptomes of embryonic, larval, and metamorphic development in the marine mollusc Aplysia californica and reveal novel molecular components associated with life history transitions. Specifically, we identify more than 20 signal peptides, putative hormones, and transcription factors in association with early development and metamorphic stages-many of which seem to be evolutionarily conserved elements of signal transduction pathways. We also characterize genes related to biomineralization-a critical process of molluscan development. In summary, our experiment provides the first large-scale survey of gene expression in mollusc development, and complements previous studies on the regulatory mechanisms underlying body plan patterning and the formation of larval and juvenile structures. This study serves as a resource for further functional annotation of transcripts and genes in Aplysia, specifically and molluscs in general. A comparison of the Aplysia developmental transcriptome with similar studies in the zebra fish Danio rerio, the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, and other studies on molluscs suggests an overall highly divergent pattern of gene regulatory mechanisms that are likely a consequence of the different developmental modes of these organisms. © 2010 Wiley-Liss, Inc., A Wiley Company.

  14. Developmental facial paralysis: a review. (United States)

    Terzis, Julia K; Anesti, Katerina


    The purpose of this study is to clarify the confusing nomenclature and pathogenesis of Developmental Facial Paralysis, and how it can be differentiated from other causes of facial paralysis present at birth. Differentiating developmental from traumatic facial paralysis noted at birth is important for determining prognosis, but also for medicolegal reasons. Given the dramatic presentation of this condition, accurate and reliable guidelines are necessary in order to facilitate early diagnosis and initiate appropriate therapy, while providing support and counselling to the family. The 30 years experience of our center in the management of developmental facial paralysis is dependent upon a thorough understanding of facial nerve embryology, anatomy, nerve physiology, and an appreciation of well-recognized mishaps during fetal development. It is hoped that a better understanding of this condition will in the future lead to early targeted screening, accurate diagnosis and prompt treatment in this population of facially disfigured patients, which will facilitate their emotional and social rehabilitation, and their reintegration among their peers.

  15. Laboratory markers in ulcerative colitis: Current insights and future advances

    Institute of Scientific and Technical Information of China (English)

    Michele; Cioffi; Antonella; De; Rosa; Rosalba; Serao; Ilaria; Picone; Maria; Teresa; Vietri


    Ulcerative colitis(UC)and Crohn’s disease(CD)are the major forms of inflammatory bowel diseases(IBD)in man.Despite some common features,these forms can be distinguished by different genetic predisposition,risk factors and clinical,endoscopic and histological characteristics.The aetiology of both CD and UC remains unknown,but several evidences suggest that CD and perhaps UC are due to an excessive immuneresponse directed against normal constituents of the intestinal bacterial flora.Tests sometimes invasive are routine for the diagnosis and care of patients with IBD.Diagnosis of UC is based on clinical symptoms combined with radiological and endoscopic investigations.The employment of non-invasive biomarkers is needed.These biomarkers have the potential to avoid invasive diagnostic tests that may result in discomfort and potential complications.The ability to determine the type,severity,prognosis and response to therapy of UC,using biomarkers has long been a goal of clinical researchers.We describe the biomarkers assessed in UC,with special reference to acute-phase proteins and serologic markers and thereafter,we describe the new biological markers and the biological markers could be developed in the future:(1)serum markers of acute phase response:The laboratory tests most used to measure the acute-phase proteins in clinical practice are the serum concentration of C-reactive protein and the erythrocyte sedimentation rate.Other biomarkers of inflammation in UC include platelet count,leukocyte count,and serum albumin and serum orosomucoid concentrations;(2)serologic markers/antibodies:In the last decades serological and immunologic biomarkers have been studied extensively in immunology and have been used in clinical practice to detect specific pathologies.In UC,the presence of these antibodies can aid as surrogate markers for the aberrant host immune response;and(3)future biomarkers:The development of biomarkers in UC will be very important in the future.The progress

  16. Left Ventricular Structure and Function in Children with and without Developmental Coordination Disorder (United States)

    Chirico, Daniele; O'Leary, Deborah; Cairney, John; Klentrou, Panagiota; Haluka, Karen; Hay, John; Faught, Brent


    Children with developmental coordination disorder (DCD) are more likely to develop cardiovascular disease risk factors such as obesity and reduced cardio-respiratory fitness. However, there is limited data using laboratory measures for assessing the risk of cardiovascular disease associated with DCD. The purpose of this study was to examine…

  17. New serological biomarkers of inflammatory bowel disease. (United States)

    Li, Xuhang; Conklin, Laurie; Alex, Philip


    Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and characterization of new serological biomarkers (identified since 2007). These include five new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibodies against chemically synthesized (Sigma) two major oligomannose epitopes, Man alpha-1,3 Man alpha-1,2 Man (SigmaMan3) and Man alpha-1,3 Man alpha-1,2 Man alpha-1,2 Man (SigmaMan4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), ALCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-like receptors (TLR) 2 and 4, and beta-defensin-1. Furthermore, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCL16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and multiplex enzyme-linked immunosorbent assay (ELISA)'s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more

  18. MicroRNAs as potential biomarkers in malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Santoni-Rugiu E


    Full Text Available Eric Santoni-Rugiu, Morten Andersen, Morten Grauslund Laboratory of Molecular Pathology, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Abstract: Malignant pleural mesothelioma (MPM, a highly lethal cancer strictly related to asbestos exposure, is usually characterized by delayed diagnosis, resistance to current therapies, and dismal prognosis. MPM is difficult to distinguish histologically from nonmalignant reactive mesothelial proliferations (RMPs as there are no clinically validated immunohistochemical markers yet and the main diagnostic criterion remains deep invasion into the pleura and underlying fat tissue, which is often not appreciable in small pleural biopsies. In this regard, microRNAs (miRNAs, given their size and stability, are particularly attractive biomarkers in formalin-fixed paraffin-embedded tissue specimens for routine pathology. Moreover, circulating miRNAs appear to be promising biomarkers for early detection and monitoring of patients with MPM. Here, we review the studies mostly performed by miRNA arrays and reverse transcription-quantitative polymerase chain reaction in formalin-fixed paraffin-embedded or frozen tissue samples, MPM cell lines, and blood/plasma/serum samples that have highlighted the potential of miRNAs as biomarkers in MPM. Certain studies have pointed to the ability of miRNAs to distinguish the different histological MPM subtypes or separate MPM from lung adenocarcinoma, and other investigations have revealed that miRNAs can aid in differentiating MPM from RMP or have prognostic value in predicting the patient outcome. Mechanistic aspects of the involvement of miRNAs in mesothelioma genesis and possible use of miRNAs as future therapeutic targets in MPM are also emphasized. Finally, limitations of the data currently obtained due to the drawbacks of reverse transcription-quantitative polymerase chain reaction, heterogeneity of MPM tissue samples, and

  19. Quantitative imaging biomarker ontology (QIBO) for knowledge representation of biomedical imaging biomarkers. (United States)

    Buckler, Andrew J; Liu, Tiffany Ting; Savig, Erica; Suzek, Baris E; Ouellette, M; Danagoulian, J; Wernsing, G; Rubin, Daniel L; Paik, David


    A widening array of novel imaging biomarkers is being developed using ever more powerful clinical and preclinical imaging modalities. These biomarkers have demonstrated effectiveness in quantifying biological processes as they occur in vivo and in the early prediction of therapeutic outcomes. However, quantitative imaging biomarker data and knowledge are not standardized, representing a critical barrier to accumulating medical knowledge based on quantitative imaging data. We use an ontology to represent, integrate, and harmonize heterogeneous knowledge across the domain of imaging biomarkers. This advances the goal of developing applications to (1) improve precision and recall of storage and retrieval of quantitative imaging-related data using standardized terminology; (2) streamline the discovery and development of novel imaging biomarkers by normalizing knowledge across heterogeneous resources; (3) effectively annotate imaging experiments thus aiding comprehension, re-use, and reproducibility; and (4) provide validation frameworks through rigorous specification as a basis for testable hypotheses and compliance tests. We have developed the Quantitative Imaging Biomarker Ontology (QIBO), which currently consists of 488 terms spanning the following upper classes: experimental subject, biological intervention, imaging agent, imaging instrument, image post-processing algorithm, biological target, indicated biology, and biomarker application. We have demonstrated that QIBO can be used to annotate imaging experiments with standardized terms in the ontology and to generate hypotheses for novel imaging biomarker-disease associations. Our results established the utility of QIBO in enabling integrated analysis of quantitative imaging data.

  20. Developmental programming of appetite/satiety. (United States)

    Ross, Michael G; Desai, Mina


    Obesity is often attributed to a Western lifestyle, a high-fat diet and decreased activity. While these factors certainly contribute to adult obesity, compelling data from our laboratory and others indicate that this explanation is oversimplified. Recent studies strongly argue that maternal/fetal under- or overnutrition predisposes the offspring to become hyperphagic and increases the risk of later obesity. Both infants small for gestational age (SGA) or infants born to obese mothers who consume a high-fat diet are at a markedly increased risk of adult obesity. Specific alterations in the fetal metabolic/energy environment directly influence the development of appetite regulatory pathways. Specifically, SGA infants demonstrate (1) impaired satiety and anorexigenic cell signaling, (2) enhanced cellular orexigenic responses, (3) programmed dysfunction of neuroprogenitor cell proliferation/differentiation, and (4) increased expression of appetite (NPY) versus satiety (POMC) neurons. In both hypothalamic tissue and ex vivo culture, SGA newborns exhibit increased levels of the nutrient sensor SIRT1, signifying reduced energy, whereas maternal high-fat-exposed newborns exhibit reduced levels of pAMPK, signifying energy excess. Via downstream regulation of bHLH neuroproliferation (Hes1) and neurodifferentiation factors (Mash1, Ngn3), neurogenesis is biased toward orexigenic and away from anorexigenic neurons, resulting in excess appetite, reduced satiety and development of obesity. Despite the developmental programming of appetite neurogenesis, the potential for neuronal remodeling raises the opportunity for novel interventions.

  1. Developmental Gene Regulation and Mechanisms of Evolution (United States)


    The Marine Biological Laboratory and the National Aeronautics and Space Administration have established a cooperative agreement with the formation of a Center for Advanced Studies 'in the Space Life Sciences (CASSLS) at the MBL. This Center serves as an interface between NASA and the basic science community, addressing issues of mutual interest. The Center for Advanced Studies 'in the Space Life Sciences provides a forum for scientists to think and discuss, often for the first time, the role that gravity and aspects of spaceflight may play 'in fundamental cellular and physiologic processes. In addition the Center will sponsor discussions on evolutionary biology. These interactions will inform the community of research opportunities that are of interest to NASA. This workshop is one of a series of symposia, workshops and seminars that will be held at the MBL to advise NASA on a wide variety of topics in the life sciences, including cell biology, developmental biology, mg evolutionary biology, molecular biology, neurobiology, plant biology and systems biology.

  2. Biomarkers for osteoarthritis: investigation, identification, and prognosis

    Directory of Open Access Journals (Sweden)

    Zhai G


    Full Text Available Guangju Zhai,1,2 Erfan Aref Eshghi11Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada; 2Department of Twin Research and Genetic Epidemiology, King's College London, London, UKAbstract: Osteoarthritis (OA is the most common form of arthritis and results in substantial morbidity and disability in the elderly, imposing a great economic burden on society. While there are drugs available on the market that mitigate pain and improve function, there are no disease-modifying osteoarthritis drugs, partly because there is no reliable method that can be used to identify early OA changes. There is a pressing need to develop reliable biomarkers that can inform on the process of joint destruction in OA. Such biomarkers could aid in drug development by identifying fast progressors and detecting early response to therapy, thus reducing patient numbers and time required for clinical trials. Over the last several years, dramatic advances in our understanding of the biochemistry of cartilage have led to a cascade of studies testing proteins as biomarkers of OA. Investigation of single-nucleotide polymorphisms as genetic biomarkers and the application of technologies such as metabolomics to OA are generating potentially additional biomarkers that could help detect early OA changes. This review summarizes the data on the investigation of biochemical and genetic markers in OA and highlights the new biomarkers that are recently reported and their application and limitation in the management of OA. However, despite the dramatic growth of knowledge concerning the discovery of a number of useful biomarkers, the real breakthrough in this area is still not achieved.Keywords: osteoarthritis, biochemical markers, metabolomics, genetics, epigenetics

  3. Introduction: biomarkers in neurodevelopment toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Needleman, H.L.


    The search for markers of toxicant exposure and effect upon the development of organisms presents a set of challenges that differ in many ways from those encountered in the study of markers in reproduction or pregnancy. These latter two fields specify a relatively narrow set of organs or biological systems. The term development, on the other hand, can apply to any organ system, or to any set of phenomena that changes in an ordered way over time. For this reason the papers presented in the session on development were chosen to narrow the focus to neurodevelopmental markers, as such markers may be altered by neurotoxic exposure. In attempting to meet this task, the authors have been able to select a group of investigators who work at the leading edges of their respective fields of developmental neuroanatomy, neurotoxicology, neuroendocrinology, neuropsychology, and infant development. The notion that toxicants could affect behavior certainly is not new. Recent knowledge that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral observation might provide early markers of effect has given rise to two new fields: behavioral toxicology and behavioral teratology.

  4. Informatics and the clinical laboratory. (United States)

    Jones, Richard G; Johnson, Owen A; Batstone, Gifford


    The nature of pathology services is changing under the combined pressures of increasing workloads, cost constraints and technological advancement. In the face of this, laboratory systems need to meet new demands for data exchange with clinical electronic record systems for test requesting and results reporting. As these needs develop, new challenges are emerging especially with respect to the format and content of the datasets which are being exchanged. If the potential for the inclusion of intelligent systems in both these areas is to be realised, the continued dialogue between clinicians and laboratory information specialists is of paramount importance. Requirements of information technology (IT) in pathology, now extend well beyond the provision of purely analytical data. With the aim of achieving seamless integration of laboratory data into the total clinical pathway, 'Informatics' - the art and science of turning data into useful information - is becoming increasingly important in laboratory medicine. Informatics is a powerful tool in pathology - whether in implementing processes for pathology modernisation, introducing new diagnostic modalities (e.g. proteomics, genomics), providing timely and evidence-based disease management, or enabling best use of limited and often costly resources. Providing appropriate information to empowered and interested patients - which requires critical assessment of the ever-increasing volume of information available - can also benefit greatly from appropriate use of informatics in enhancing self-management of long term conditions. The increasing demands placed on pathology information systems in the context of wider developmental change in healthcare delivery are explored in this review. General trends in medical informatics are reflected in current priorities for laboratory medicine, including the need for unified electronic records, computerised order entry, data security and recovery, and audit. We conclude that there is a

  5. Sleep duration, cardiovascular disease, and proinflammatory biomarkers

    Directory of Open Access Journals (Sweden)

    Grandner MA


    Full Text Available Michael A Grandner,1,2 Megan R Sands-Lincoln,3 Victoria M Pak,2,4 Sheila N Garland1,5 1Behavioral Sleep Medicine Program, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, PA, USA; 2Center for Sleep and Circadian Neurobiology, University of Pennsylvania, PA, USA; 3Center for Evidence Based Medicine, Elsevier Inc, Philadelphia, PA, USA; 4Division of Sleep Medicine, Perelman School of Medicine, University of Pennsylvania, PA, USA; 5Department of Family Medicine and Community Health, Perelman School of Medicine, University of Pennsylvania, PA, USA Abstract: Habitual sleep duration has been associated with cardiometabolic disease, via several mechanistic pathways, but few have been thoroughly explored. One hypothesis is that short and/or long sleep duration is associated with a proinflammatory state, which could increase risk for cardiovascular and metabolic diseases. This hypothesis has been largely explored in the context of experimental sleep deprivation studies which have attempted to demonstrate changes in proinflammatory markers following acute sleep loss in the laboratory. Despite the controlled environment available in these studies, samples tend to lack generalization to the population at large and acute sleep deprivation may not be a perfect analog for short sleep. To address these limitations, population based studies have explored associations between proinflammatory markers and habitual sleep duration. This review summarizes what is known from experimental and cross-sectional studies about the association between sleep duration, cardiovascular disease, and proinflammatory biomarkers. First, the association between sleep duration with both morbidity and mortality, with a focus on cardiovascular disease, is reviewed. Then, a brief review of the potential role of proinflammatory markers in cardiovascular disease is presented. The majority of this review details specific findings related to specific

  6. Auditory Processing in Noise: A Preschool Biomarker for Literacy.

    Directory of Open Access Journals (Sweden)

    Travis White-Schwoch


    Full Text Available Learning to read is a fundamental developmental milestone, and achieving reading competency has lifelong consequences. Although literacy development proceeds smoothly for many children, a subset struggle with this learning process, creating a need to identify reliable biomarkers of a child's future literacy that could facilitate early diagnosis and access to crucial early interventions. Neural markers of reading skills have been identified in school-aged children and adults; many pertain to the precision of information processing in noise, but it is unknown whether these markers are present in pre-reading children. Here, in a series of experiments in 112 children (ages 3-14 y, we show brain-behavior relationships between the integrity of the neural coding of speech in noise and phonology. We harness these findings into a predictive model of preliteracy, revealing that a 30-min neurophysiological assessment predicts performance on multiple pre-reading tests and, one year later, predicts preschoolers' performance across multiple domains of emergent literacy. This same neural coding model predicts literacy and diagnosis of a learning disability in school-aged children. These findings offer new insight into the biological constraints on preliteracy during early childhood, suggesting that neural processing of consonants in noise is fundamental for language and reading development. Pragmatically, these findings open doors to early identification of children at risk for language learning problems; this early identification may in turn facilitate access to early interventions that could prevent a life spent struggling to read.

  7. Laboratory Information Systems. (United States)

    Henricks, Walter H


    Laboratory information systems (LISs) supply mission-critical capabilities for the vast array of information-processing needs of modern laboratories. LIS architectures include mainframe, client-server, and thin client configurations. The LIS database software manages a laboratory's data. LIS dictionaries are database tables that a laboratory uses to tailor an LIS to the unique needs of that laboratory. Anatomic pathology LIS (APLIS) functions play key roles throughout the pathology workflow, and laboratories rely on LIS management reports to monitor operations. This article describes the structure and functions of APLISs, with emphasis on their roles in laboratory operations and their relevance to pathologists.

  8. New serological biomarkers of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Xuhang Li; Laurie Conldin; Philip Alex


    Serological biomarkers in inflammatory bowel disease(IBD)are a rapidty expanding list of non-invasive tests for objective assessments of disease activity,early diagnosis,prognosis evaluation and surveillance.This review summarizes both old and new biomarkers in IBD,but focuses on the development and characterization of new serological iomarkers(identified since 2007).These include five new anti-glycan antibodies,anti-chitobioside IgA(ACCA),anti-laminaribioside IgG(ALCA),anti-manobioside IgG(AMCA),and antibodies against chemically synthesized(∑)two major oligomannose epitopes,Man α-1,3 Man α-1,2 Man(∑Man3)and Man α-1,3 Man α-1,2 Man α-1,2 Man(∑Man4).These new biomarkers erve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease(CD),ulcerative colitis(UC),normal and other non-IBD gut diseases,but also in predicting disease involvement(ileum vs colon),IBD risk(as subclinical biomarkers),and disease course(risk of complication and surgery).Interestingly,the prevalence of he antiglycan antibodies,including anti-Saccharomyces cerevisiae antibodies(ASCA),ALCA and AMCA,was found to be associated with single nucleotide polymorphisms(SNPs)of IBD susceptible genes such as NOD2/CARDl5,NOD1/CARD4,toll-like receptors(TLR)2 and 4,and β-defensin-1.Further more,a gene dosage effect was observed:anti-glycan positivity became more requent as the number of NOD2/CARDl5 SNPS increased.Other new serum/plasma IBD biomarkers reviewed include ubiquitination factor E4A(UBE4A),CXCL16(a chemokine),resistin,and apolipoprotein A-Ⅳ.This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics,fourier transform near-infrared spectroscopy,and multiplex enzyme-linked immunosorbent assay(ELISA)'s(with an emphasis on cytokine/chemokine profiling).Finally,the prospects of developing more clinically useful novel diagnostic algorithms by incorporating new technologies in

  9. Biomarkers of Parkinson's disease: present and future. (United States)

    Miller, Diane B; O'Callaghan, James P


    Sporadic or idiopathic Parkinson's disease (PD) is an age-related neurodegenerative disorder of unknown origin that ranks only second behind Alzheimer's disease (AD) in prevalence and its consequent social and economic burden. PD neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta; however, more widespread involvement of other CNS structures and peripheral tissues now is widely documented. The onset of molecular and cellular neuropathology of PD likely occurs decades before the onset of the motor symptoms characteristic of PD. The hallmark symptoms of PD, resting tremors, rigidity and postural disabilities, are related to dopamine (DA) deficiency. Current therapies treat these symptoms by replacing or boosting existing DA. All current interventions have limited therapeutic benefit for disease progression because damage likely has progressed over an estimated period of ~5 to 15years to a loss of 60%-80% of the nigral DA neurons, before symptoms emerge. There is no accepted definitive biomarker of PD. An urgent need exists to develop early diagnostic biomarkers for two reasons: (1) to intervene at the onset of disease and (2) to monitor the progress of therapeutic interventions that may slow or stop the course of the disease. In the context of disease development, one of the promises of personalized medicine is the ability to predict, on an individual basis, factors contributing to the susceptibility for the development of a given disease. Recent advances in our understanding of genetic factors underlying or contributing to PD offer the potential for monitoring susceptibility biomarkers that can be used to identify at-risk individuals and possibly prevent the onset of disease through treatment. Finally, the exposome concept is new in the biomarker discovery arena and it is suggested as a way to move forward in identifying biomarkers of neurological diseases. It is a two-stage scheme involving a first stage

  10. Energy Materials Research Laboratory (EMRL) (United States)

    Federal Laboratory Consortium — The Energy Materials Research Laboratory at the Savannah River National Laboratory (SRNL) creates a cross-disciplinary laboratory facility that lends itself to the...

  11. Biomarkers for wound healing and their evaluation. (United States)

    Patel, S; Maheshwari, A; Chandra, A


    A biological marker (biomarker) is a substance used as an indicator of biological state. Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Research has identified several cellular events and mediators associated with wound healing that can serve as biomarkers. Macrophages, neutrophils, fibroblasts and platelets release cytokines molecules including TNF-α, interleukins (ILs) and growth factors, of which platelet-derived growth factor (PDGF) holds the greatest importance. As a result, various white cells and connective tissue cells release both matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). Studies have demonstrated that IL-1, IL-6, and MMPs, levels above normal, and an abnormally high MMP/TIMP ratio are often present in non-healing wounds. Clinical examination of wounds for these mediators could predict which wounds will heal and which will not, suggesting use of these chemicals as biomarkers of wound healing. There is also evidence that the application of growth factors like PDGF will alleviate the recuperating process of chronic, non-healing wounds. Finding a specific biomarker for wound healing status would be a breakthrough in this field and helping treat impaired wound healing.

  12. Biomarkers in the Management of Difficult Asthma. (United States)

    Schleich, Florence; Demarche, Sophie; Louis, Renaud


    Difficult asthma is a heterogeneous disease of the airways including various types of bronchial inflammation and various degrees of airway remodeling. Therapeutic response of severe asthmatics can be predicted by the use of biomarkers of Type2-high or Type2-low inflammation. Based on sputum cell analysis, four inflammatory phenotypes have been described. As induced sputum is timeconsuming and expensive technique, surrogate biomarkers are useful in clinical practice. Eosinophilic phenotype is likely to reflect ongoing adaptive immunity in response to allergen. Several biomarkers of eosinophilic asthma are easily available in clinical practice (blood eosinophils, serum IgE, exhaled nitric oxyde, serum periostin). Neutrophilic asthma is thought to reflect innate immune system activation in response to pollutants or infectious agents while paucigranulocytic asthma is thought to be not inflammatory and characterized by smooth muscle dysfunction. We currently lack of user-friendly biomarkers of neutrophilic asthma and airway remodeling. In this review, we summarize the biomarkers available for the management of difficult asthma.

  13. Fish metalloproteins as biomarkers of environmental contamination. (United States)

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


    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.

  14. Proteome-based biomarkers in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Chen Sun; Ann H Rosendahl; Daniel Ansari; Roland Andersson


    Pancreatic cancer, as a highly malignant cancer and the fourth cause of cancer-related death in world, is characterized by dismal prognosis, due to rapid disease progression, highly invasive tumour phenotype, and resistance to chemotherapy. Despite significant advances in treatment of the disease during the past decade,the survival rate is little improved. A contributory factor to the poor outcome is the lack of appropriate sensitive and specific biomarkers for early diagnosis. Furthermore, biomarkers for targeting, directing and assessing therapeutic intervention, as well as for detection of residual or recurrent cancer are also needed. Thus, the identification of adequate biomarkers in pancreatic cancer is of extreme importance. Recently, accompanying the development of proteomic technology and devices, more and more potential biomarkers have appeared and are being reported. In this review, we provide an overview of the role of proteome-based biomarkers in pancreatic cancer, including tissue, serum, juice, urine and cell lines. We also discuss the possible mechanism and prospects in the future. That information hopefully might be helpful for further research in the field.

  15. Life history evolution and comparative developmental biology of echinoderms. (United States)

    Hart, Michael W


    Evolutionary biologists studying life history variation have used echinoderms in experimental, laboratory, and field studies of life history evolution. This focus on echinoderms grew originally from the tradition of comparative embryology, in which echinoderms were central. The tools for obtaining and manipulating echinoderm gametes and larvae were taken directly from comparative embryological research. In addition, the comparative embryologists employed a diverse array of echinoderms, not a few model species, and this diversity has led to a broad understanding of the development, function, and evolution of echinoderm larvae. As a result, this branch of life history evolution has deep roots in comparative developmental biology of echinoderms. Here two main aspects of this relationship are reviewed. The first is a broad range of studies of fertilization biology, dispersal, population genetics, functional morphology, and asexual reproduction in which developmental biologists might take a keen interest because of the historical origins of this research in echinoderm comparative embryology. The second is a similarly broad variety of topics in life history research in which evolutionary biologists require techniques or data from developmental biology in order to make progress on understanding patterns of life history variation among echinoderm species and higher taxa. Both sets of topics provide opportunities for interaction and collaboration.

  16. Developmental modes and developmental mechanisms can channel brain evolution

    Directory of Open Access Journals (Sweden)

    Christine J Charvet


    Full Text Available Anseriform birds (ducks and geese as well as parrots and songbirds have evolved a disproportionately enlarged telencephalon compared with many other birds. However, parrots and songbirds differ from anseriform birds in their mode of development. Whereas ducks and geese are precocial (e.g., hatchlings feed on their own, parrots and songbirds are altricial (e.g., hatchlings are fed by their parents. We here consider how developmental modes may limit and facilitate specific changes in the mechanisms of brain development. We suggest that altriciality facilitates the evolution of telencephalic expansion by delaying telencephalic neurogenesis. We further hypothesize that delays in telencephalic neurogenesis generate delays in telencephalic maturation, which in turn foster neural adaptations that facilitate learning. Specifically, we propose that delaying telencephalic neurogenesis was a prerequisite for the evolution of neural circuits that allow parrots and songbirds to produce learned vocalizations. Overall, we argue that developmental modes have influenced how some lineages of birds increased the size of their telencephalon and that this, in turn, has influenced subsequent changes in brain circuits and behavior.

  17. Developmental Modes and Developmental Mechanisms can Channel Brain Evolution. (United States)

    Charvet, Christine J; Striedter, Georg F


    Anseriform birds (ducks and geese) as well as parrots and songbirds have evolved a disproportionately enlarged telencephalon compared with many other birds. However, parrots and songbirds differ from anseriform birds in their mode of development. Whereas ducks and geese are precocial (e.g., hatchlings feed on their own), parrots and songbirds are altricial (e.g., hatchlings are fed by their parents). We here consider how developmental modes may limit and facilitate specific changes in the mechanisms of brain development. We suggest that altriciality facilitates the evolution of telencephalic expansion by delaying telencephalic neurogenesis. We further hypothesize that delays in telencephalic neurogenesis generate delays in telencephalic maturation, which in turn foster neural adaptations that facilitate learning. Specifically, we propose that delaying telencephalic neurogenesis was a prerequisite for the evolution of neural circuits that allow parrots and songbirds to produce learned vocalizations. Overall, we argue that developmental modes have influenced how some lineages of birds increased the size of their telencephalon and that this, in turn, has influenced subsequent changes in brain circuits and behavior.

  18. Developmental robotics: manifesto and application. (United States)

    Elliott, Terry; Shadbolt, Nigel R


    We argue that all embodied organisms, whether robots or animals, face the same challenge: of adapting to bodies, brains and environments that undergo constant and inevitable change. After highlighting the evidence for the universal role of a class of molecular factors called neurotrophic factors in the response of animals to this challenge, we suggest that implementing models of neurotrophic interactions on robots may confer on them the adaptability and robustness exhibited by animals. We briefly review a mathematical model of neurotrophic interactions and then discuss its application in a robotic context. Finally, we examine the potential, or otherwise, of our approach to developmental robotics.

  19. Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss.

    Directory of Open Access Journals (Sweden)

    Christian Dejaco

    Full Text Available Previous studies suggest a role for eotaxin-3, TARC/CCL17 and IgG4 in newly-diagnosed patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss with highly active disease. The role of these biomarkers in relapsing disease is unclear.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio were determined in serum samples from a longitudinal cohort of patients with EGPA (105 visits of 25 patients. Epidemiological, clinical and laboratory data were available for all visits.At the first visit, 80% of patients were using glucocorticoids and 68% additional immunosuppressive drugs. Disease flares were seen at 18 visits. The median BVAS and BVAS/WG scores at time of relapse were 4 and 2, respectively. None of the biomarkers tested were useful to discriminate between active disease and remission. Patients treated with prednisone had lower eotaxin-3 and eosinophil levels compared to patients not taking glucocorticoids irrespective of disease activity. Use of immunosuppressive agents was not associated with biomarker levels.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio do not clearly differentiate active and inactive disease in established EGPA. Defining biomarkers in EGPA remains a challenge especially during times of glucocorticoid use.

  20. Urinary biomarkers for prostate cancer: a review

    Institute of Scientific and Technical Information of China (English)

    Daphne Hessels; Jack A Schalken


    Although the routine use of serum prostate-specific antigen (PSA) testing has undoubtedly increased prostate cancer (PCa) detection,one of its main drawbacks is its lack of specificity.As a consequence,many men undergo unnecessary biopsies or treatments for indolent tumours.PCa-specific markers are needed for the early detection of the disease and the prediction of aggressiveness of a prostate tumour.Since PCa is a heterogeneous disease,a panel of tumour markers is fundamental for a more precise diagnosis.Several biomarkers are promising due to their specificity for the disease in tissue.However,tissue is unsuitable as a possible screening tool.Since urine can be easily obtained in a non-invasive manner,it is a promising substrate for biomarker testing.This article reviews the biomarkers for the non-invasive testing of PCa in urine.

  1. Advances in biomarkers of major depressive disorder. (United States)

    Huang, Tiao-Lai; Lin, Chin-Chuen


    Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Biomarkers are measurable indicators that could help diagnosing MDD or predicting treatment response. In this chapter, lipid profiles, immune/inflammation, and neurotrophic factor pathways that have long been implicated in the pathogenesis of MDD are discussed. Then, pharmacogenetics and epigenetics of serotonin transport and its metabolism pathway, brain-derived neurotrophic factor, and abnormality of hypothalamo-pituitary-adrenocortical axis also revealed new biomarkers. Lastly, new techniques, such as proteomics and metabolomics, which allow researchers to approach the studying of MDD with new directions and make new discoveries are addressed. In the future, more data are needed regarding pathophysiology of MDD, including protein levels, single nucleotide polymorphism, epigenetic regulation, and clinical data in order to better identify reliable and consistent biomarkers for diagnosis, treatment choice, and outcome prediction.

  2. Using Aptamers for Cancer Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Yun Min Chang


    Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.


    Directory of Open Access Journals (Sweden)

    Lei Zhang


    Full Text Available Early detection of cancer biomarkers with high precision is critically important for cancer therapy. A variety of sensors based on different nanostructured materials have attracted intensive research interest due to their potential for highly sensitive and selective detection of cancer biomarkers. This review covers the use of a variety of nanostructured materials, including carbon nanotubes, silicon nanowires, gold nanoparticles and quantum dots, in the fabrication of sensors. Emphases are placed on how the detection systems work and what detection limits can be achieved. Some assays described in this review outperform established methods for cancer biomarker detection. It is highly promising that these sensors would soon move into commercial-scale production and find routine use in hospitals.

  4. Current early diagnostic biomarkers of prostate cancer

    Directory of Open Access Journals (Sweden)

    Min Qu


    Full Text Available Prostate cancer (PCa has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers.

  5. Use of cardiac biomarkers in neonatology. (United States)

    Vijlbrief, Daniel C; Benders, Manon J N L; Kemperman, Hans; van Bel, Frank; de Vries, Willem B


    Cardiac biomarkers are used to identify cardiac disease in term and preterm infants. This review discusses the roles of natriuretic peptides and cardiac troponins. Natriuretic peptide levels are elevated during atrial strain (atrial natriuretic peptide (ANP)) or ventricular strain (B-type natriuretic peptide (BNP)). These markers correspond well with cardiac function and can be used to identify cardiac disease. Cardiac troponins are used to assess cardiomyocyte compromise. Affected cardiomyocytes release troponin into the bloodstream, resulting in elevated levels of cardiac troponin. Cardiac biomarkers are being increasingly incorporated into clinical trials as indicators of myocardial strain. Furthermore, cardiac biomarkers can possibly be used to guide therapy and improve outcome. Natriuretic peptides and cardiac troponins are potential tools in the diagnosis and treatment of neonatal disease that is complicated by circulatory compromise. However, clear reference ranges need to be set and validation needs to be carried out in a population of interest.

  6. Flavonoids as fruit and vegetable intake biomarkers

    DEFF Research Database (Denmark)

    Krogholm, Kirstine Suszkiewicz

    correlation coefficients between total fruit, juice, tea and vegetable intake estimated by FFQ and each of the biomarkers. This finding, of a statistically significant correlation between the Inter99 FFQ and two independent biomarkers indicates that the Inter99 FFQ provides a useful estimate of the overall...... dietary intake of fruits, juices, tea and vegetables in the Inter99 cohort. VCs for the FFQ ranged from 0.43-0.68 using 24h urine and from 0.35-0.64 using morning spot urine, indicating that the intake of fruits, juice, tea and vegetables was reflected by flavonoids both in morning spot and 24h urine...... of fruit and vegetable intake (Nielsen et al. 2002). The overall aim of the present Ph.D. thesis was to further develop and validate this potentially new fruit and vegetable biomarker and furthermore use it for the validation of self-reported dietary intake of fruits and vegetables in intervention...

  7. Reappraisal of hydrocarbon biomarkers in Archean rocks (United States)

    French, Katherine L.; Hallmann, Christian; Hope, Janet M.; Schoon, Petra L.; Zumberge, J. Alex; Hoshino, Yosuke; Peters, Carl A.; George, Simon C.; Love, Gordon D.; Brocks, Jochen J.; Buick, Roger; Summons, Roger E.


    Hopanes and steranes found in Archean rocks have been presented as key evidence supporting the early rise of oxygenic photosynthesis and eukaryotes, but the syngeneity of these hydrocarbon biomarkers is controversial. To resolve this debate, we performed a multilaboratory study of new cores from the Pilbara Craton, Australia, that were drilled and sampled using unprecedented hydrocarbon-clean protocols. Hopanes and steranes in rock extracts and hydropyrolysates from these new cores were typically at or below our femtogram detection limit, but when they were detectable, they had total hopane (oxygenic photosynthesis and eukaryotes by ∼2.7 billion years ago. Although suitable Proterozoic rocks exist, no currently known Archean strata lie within the appropriate thermal maturity window for syngenetic hydrocarbon biomarker preservation, so future exploration for Archean biomarkers should screen for rocks with milder thermal histories.

  8. Early Intervention in Children with Developmental Disabilities


    Beena Johnson


    Developmental disabilities consist of conditions that delay or impair the physical, cognitive, and/or psychological development of children. If not intervened at the earliest, these disabilities will cause significant negative impact on multiple domains of functioning such as learning, language, self-care and capacity for independent living. Common developmental disabilities include autism spectrum disorders, intellectual disabilities, developmental delay and cerebral palsy. About one fourth...

  9. An Introduction to Evolutionary Developmental Psychology

    Directory of Open Access Journals (Sweden)

    Karin Machluf


    Full Text Available Evolutionary developmental psychology represents a synthesis of modern evolutionary theory and developmental psychology. Here we introduce the special issue on evolutionary developmental psychology by briefly discussing the history of this field and then summarizing the variety of topics that are covered. In this special issue, leading researchers provide a collection of theoretical and empirical articles that highlight recent findings and propose promising areas for future research.

  10. An introduction to evolutionary developmental psychology. (United States)

    Machluf, Karin; Liddle, James R; Bjorklund, David F


    Evolutionary developmental psychology represents a synthesis of modern evolutionary theory and developmental psychology. Here we introduce the special issue on evolutionary developmental psychology by briefly discussing the history of this field and then summarizing the variety of topics that are covered. In this special issue, leading researchers provide a collection of theoretical and empirical articles that highlight recent findings and propose promising areas for future research.

  11. MSU-DOE Plant Research Laboratory

    Energy Technology Data Exchange (ETDEWEB)


    This document is the compiled progress reports of research funded through the Michigan State University/Department of Energy Plant Research Laboratory. Fourteen reports are included, covering the molecular basis of plant/microbe symbiosis, cell wall biosynthesis and proteins, gene expression, stress responses, plant hormone biosynthesis, interactions between the nuclear and organelle genomes, sensory transduction and tropisms, intracellular sorting and trafficking, regulation of lipid metabolism, molecular basis of disease resistance and plant pathogenesis, developmental biology of Cyanobacteria, and hormonal involvement in environmental control of plant growth. 320 refs., 26 figs., 3 tabs. (MHB)

  12. Fluid biomarkers in multiple system atrophy: A review of the MSA Biomarker Initiative. (United States)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy; Gerhard, Alexander; Jellinger, Kurt; Jeromin, Andreas; Krismer, Florian; Mollenhauer, Brit; Schlossmacher, Michael G; Shaw, Leslie M; Verbeek, Marcel M; Wenning, Gregor K; Winge, Kristian; Zhang, Jing; Meissner, Wassilios G


    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results suggest that combining several CSF fluid biomarkers may be more successful than using single markers, at least for the diagnosis. Currently, the clinically most useful markers may comprise a combination of the light chain of neurofilament (which is consistently elevated in MSA compared to controls and Parkinson's disease), metabolites of the catecholamine pathway and proteins such as α-synuclein, DJ-1 and total-tau. Beyond future efforts in biomarker discovery, the harmonization of standard operating procedures will be crucial for future success.

  13. Sexual dysfunction within an adult developmental perspective. (United States)

    Fagan, P J; Meyer, J K; Schmidt, C W


    The focus of this paper is on the adult who has adequately mastered the oedipal stage of psychosexual development and who presents with a sexual dysfunction. Drawing on the developmental sequence of Erik Erikson, the authors suggest that failure to address adequately an adult psychosocial crisis may result in sexual dysfunction. There may be both adult developmental deficits and regression to adolescent and adult stages previously negotiated. Both may be symptomatically represented by sexual dysfunction. The authors urge that the sexual and marital problems be evaluated within an adult developmental framework and that the therapy address the psychosocial issues which are appropriate to the developmental stage of the patient.

  14. Context Matters: Support for Leader Developmental Readiness. (United States)

    Thompson, Sara E; Reichard, Rebecca J


    Leader developers need to consider support for leader developmental readiness by examining organizational culture, job design and rewards, social support, and availability and structure of leader development programming.

  15. Piaget's Structural Developmental Psychology. v. Ideology-Critique and the Possibility of a Critical Developmental Theory. (United States)

    Broughton, John M.


    This final essay in a five-part series examining Piaget's structural developmental psychology suggests that a psychological theory which integrates aspects of developmental structuralism within a critical social framework can be developed. (Author/RH)

  16. Next-Generation Biomarkers of Health. (United States)

    van Ommen, Ben; Wopereis, Suzan


    Current biomarkers used in health care and in nutrition and health research are based on quantifying disease onset and its progress. Yet, both health care and nutrition should focus on maintaining optimal health, where the related biology is essentially differing from biomedical science. Health is characterized by the ability to continuously adapt in varying circumstances where multiple mechanisms of systems flexibility are involved. A new generation of biomarkers is needed that quantifies all aspects of systems flexibility, opening the door to real lifestyle-related health optimization, self-empowerment, and related products and services.

  17. Stable Feature Selection for Biomarker Discovery

    CERN Document Server

    He, Zengyou


    Feature selection techniques have been used as the workhorse in biomarker discovery applications for a long time. Surprisingly, the stability of feature selection with respect to sampling variations has long been under-considered. It is only until recently that this issue has received more and more attention. In this article, we review existing stable feature selection methods for biomarker discovery using a generic hierarchal framework. We have two objectives: (1) providing an overview on this new yet fast growing topic for a convenient reference; (2) categorizing existing methods under an expandable framework for future research and development.

  18. Developmental constraint of insect audition

    Directory of Open Access Journals (Sweden)

    Strauß Johannes


    Full Text Available Abstract Background Insect ears contain very different numbers of sensory cells, from only one sensory cell in some moths to thousands of sensory cells, e.g. in cicadas. These differences still await functional explanation and especially the large numbers in cicadas remain puzzling. Insects of the different orders have distinct developmental sequences for the generation of auditory organs. These sensory cells might have different functions depending on the developmental stages. Here we propose that constraints arising during development are also important for the design of insect ears and might influence cell numbers of the adults. Presentation of the hypothesis We propose that the functional requirements of the subadult stages determine the adult complement of sensory units in the auditory system of cicadas. The hypothetical larval sensory organ should function as a vibration receiver, representing a functional caenogenesis. Testing the hypothesis Experiments at different levels have to be designed to test the hypothesis. Firstly, the neuroanatomy of the larval sense organ should be analyzed to detail. Secondly, the function should be unraveled neurophysiologically and behaviorally. Thirdly, the persistence of the sensory cells and the rebuilding of the sensory organ to the adult should be investigated. Implications of the hypothesis Usually, the evolution of insect ears is viewed with respect to physiological and neuronal mechanisms of sound perception. This view should be extended to the development of sense organs. Functional requirements during postembryonic development may act as constraints for the evolution of adult organs, as exemplified with the auditory system of cicadas.

  19. Recent Advances on Lipid Biomarkers in Marine Sediments

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-lin


    This paper reviews the recent advances of marine biomarker. Biomarkers of marine microorganisms are also included. It is important to the origin of marine biological and the monitor and evaluation of marine environment.

  20. Tau/Amyloid Beta 42 Peptide Test (Alzheimer Biomarkers) (United States)

    ... Was this page helpful? Also known as: Alzheimer Biomarkers Formal name: Tau Protein and Amyloid Beta 42 ... being researched for their potential use as AD biomarkers. If someone has symptoms of dementia , a health ...

  1. Lawrence Livermore National Laboratory Workshop Characterization of Pathogenicity, Virulence and Host-Pathogen Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, A


    The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improving our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers/scientists in the

  2. Product Evaluation Laboratory (United States)

    Federal Laboratory Consortium — This laboratory offers the services of highly trained and experienced specialists that have a full complement of measuring equipment. It is equipped with two optical...

  3. Aquatic Research Laboratory (ARL) (United States)

    Federal Laboratory Consortium — Columbia River and groundwater well water sources are delivered to the Aquatic Research Laboratory (ARL), where these resources are used to conduct research on fish...

  4. Laboratory of Biological Modeling (United States)

    Federal Laboratory Consortium — The Laboratory of Biological Modeling is defined by both its methodologies and its areas of application. We use mathematical modeling in many forms and apply it to...

  5. Laboratory of Biological Modeling (United States)

    Federal Laboratory Consortium — The Laboratory of Biological Modeling is defined by both its methodologies and its areas of application. We use mathematical modeling in many forms and apply it to a...

  6. Los Alamos National Laboratory (United States)

    Federal Laboratory Consortium — The Lab has a proud history and heritage of almost 70 years of science and innovation. The people at the Laboratory work on advanced technologies to provide the best...


    Federal Laboratory Consortium — This laboratory contains equipment to fabricate and test prototype packages of many types and sizes (e.g., bags, pouches, trays, cartons, etc.). This equipment can...

  8. Mechanical Testing Laboratory (United States)

    Federal Laboratory Consortium — NETL’s Mechanical Testing Laboratory in Albany, OR, helps researchers investigate materials that can withstand the heat and pressure commonly found in fossil energy...

  9. Philadelphia District Laboratory (PHI) (United States)

    Federal Laboratory Consortium — Program Capabilities PHI-DO Pharmaceutical Laboratory specializes in the analyses of all forms and types of drug products.Its work involves nearly all phases of drug...

  10. Geometric Design Laboratory (United States)

    Federal Laboratory Consortium — Purpose: The mission of the Geometric Design Laboratory (GDL) is to support the Office of Safety Research and Development in research related to the geometric design...

  11. Space Systems Laboratory (SSL) (United States)

    Federal Laboratory Consortium — The Space Systems Laboratory (SSL) is part of the Aerospace Engineering Department and A. James Clark School of Engineering at the University of Maryland in College...

  12. Detroit District Laboratory (DET) (United States)

    Federal Laboratory Consortium — Program CapabilitiesDET-DO Laboratory is equipped with the usual instrumentation necessary to perform a wide range of analyses of food, drugs and cosmetics. Program...

  13. Clinical Laboratory Fee Schedule (United States)

    U.S. Department of Health & Human Services — Outpatient clinical laboratory services are paid based on a fee schedule in accordance with Section 1833(h) of the Social Security Act. The clinical laboratory fee...

  14. Aircraft Fire Protection Laboratory (United States)

    Federal Laboratory Consortium — The Navy Aircraft Protection Laboratory provides complete test support for all Navy air vehicle fire protection systems.The facility allows for the simulation of a...

  15. Radiochemical Processing Laboratory (RPL) (United States)

    Federal Laboratory Consortium — The Radiochemical Processing Laboratory (RPL)�is a scientific facility funded by DOE to create and implement innovative processes for environmental clean-up and...

  16. Detroit District Laboratory (DET) (United States)

    Federal Laboratory Consortium — Program Capabilities DET-DO Laboratory is equipped with the usual instrumentation necessary to perform a wide range of analyses of food, drugs and cosmetics. Program...

  17. High Bay Laboratory (United States)

    Federal Laboratory Consortium — This laboratory is a specially constructed facility with elevated (37 feet) ceilings and an overhead catwalk, and which is dedicated to research efforts in reducing...

  18. Laboratory Demographics Lookup Tool (United States)

    U.S. Department of Health & Human Services — This website provides demographic information about laboratories, including CLIA number, facility name and address, where the laboratory testing is performed, the...

  19. Human Factors Laboratory (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  20. Geological Services Laboratory (United States)

    Federal Laboratory Consortium — Researchers use computed tomography (CT) scanners at NETL’s Geological Services Laboratory in Morgantown, WV, to peer into geologic core samples to determine how...

  1. Philadelphia District Laboratory (PHI) (United States)

    Federal Laboratory Consortium — Program CapabilitiesPHI-DO Pharmaceutical Laboratory specializes in the analyses of all forms and types of drug products.Its work involves nearly all phases of drug...

  2. Protective Systems Laboratory (United States)

    Federal Laboratory Consortium — This laboratory is a 40 by 28 by 9 foot facility that is equipped with tools for the development of various items of control technology related to the transmission...

  3. Neutral Buoyancy Laboratory (NBL) (United States)

    Federal Laboratory Consortium — The Neutral Buoyancy Laboratory (NBL) is an astronaut training facility and neutral buoyancy pool operated by NASA and located at the Sonny Carter Training Facility,...

  4. Aircraft Fire Protection Laboratory (United States)

    Federal Laboratory Consortium — The Navy Aircraft Protection Laboratory provides complete test support for all Navy air vehicle fire protection systems. The facility allows for the simulation of a...

  5. Energetics Laboratory Facilities (United States)

    Federal Laboratory Consortium — These energetic materials laboratories are equipped with explosion proof hoods with blow out walls for added safety, that are certified for safe handling of primary...

  6. Moriah Wind System Laboratory (United States)

    Federal Laboratory Consortium — Purpose: The Moriah Wind System Laboratory provides in-service support for the more than 50 U.S. Navy, U.S. Coast Guard and Military Sealift Command ships on which...

  7. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Cristina Gluhovschi


    Full Text Available Diabetic nephropathy (DN is a frequent and severe complication of diabetes mellitus (DM. Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.


    Serum biomarkers to identify susceptibility to disease in aged humans are well researched. On the other hand, our understanding of biomarkers in animal models of aging is limited. Hence, we applied a commercially available panel of 58 serum analytes to screen for possible biomark...

  9. Protein biomarker enrichment by biomarker antibody complex elution for immunoassay biosensing. (United States)

    Sabatte, Gwenola; Feitsma, Harma; Evers, Toon H; Prins, Menno W J


    It is very challenging to perform sample enrichment for protein biomarkers because proteins can easily change conformation and denature. In this paper we demonstrate protein enrichment suited for high-sensitivity integrated immuno-biosensing. The method enhances the concentration of the biomarkers and simultaneously removes matrix components that could interfere with the immunoassay. Biomarkers are captured using antibody coated magnetic particles and the biomarker antibody complexes are released by enzymatic elution. The eluted complexes are subsequently detected in a sandwich immunoassay biosensor. A scaling study of the enrichment process demonstrates an enrichment factor of 15 in buffer and plasma. We analyze the enrichment factor in terms of the three basic steps of the assay (capture, concentration, elution) and we quantify their respective efficiencies. The process is suited for integration into bio-analytical tools.

  10. Isorenieratene: Biomarker for Photic Layer Anoxia? (United States)

    Casford, J.


    The use of biomarkers is a relatively new and growing field and while these novel proxies hold the potential to revolutionise our understanding of past environments it is important that we fully understand the assumptions that underlie their use and the systems in which they operate. The use of the biomarker, isorenieratene to identify photic layer anoxia, particularly in marine systems is increasing. However recent papers have identified this carotenoid in settings that also show evidence of deep ventilation. This synthesis will assess the history and evidence for the use of this biomarker, focusing on the diagenesis of isorenieratene and the habitat of the Chlorobiaceae species that are its main producers. While it is clear this biomarker can be produced under euxinic condition in the photic layer I highlight evidence that: 1) The most common occurrence of these Chlorobiaceae species is photolithotropic and that even in marine systems it preferentially occurs at the sediment water interface rather than in pelagic conditions; 2) That these species are not the only source of this pigment and its products; and 3) These species can also operate in common micro - niches within more oxic environments.

  11. Imaging biomarkers in primary brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)


    We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

  12. Biomarkers for Major Depressive Disorder: Economic Considerations. (United States)

    Bogavac-Stanojevic, Natasa; Lakic, Dragana


    Preclinical Research Major depressive disorder (MDD) is a major psychiatric illness and it is predicted to be the second leading cause of disability by 2020 with a lifetime prevalence of about 13%. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used therapeutic class for MDD. However, response to SSRI treatment varies considerably between patients. Biomarkers of treatment response may enable clinicians to target the appropriate drug for each patient. Biomarkers need to have accuracy in real life, sensitivity, specificity, and relevance to depression. Introduction of MDD biomarkers into the health care system can increase the overall cost of clinical diagnosis of patients. Because of that, decisions to allocate health research funding must be based on drug effectiveness and cost-effectiveness. The assessment of MDD biomarkers should include reliable evidence of associated drug effectiveness, adverse events and consequences (reduced productivity and quality of life, disability) and effectiveness of alternative approaches, other drug classes or behavioral or alternative therapies. In addition, all the variables included in an economic model (probabilities, outcomes, and costs) should be based on reliable evidence gained from the literature-ideally meta-analyses-and the evidence should also be determined by informed and specific expert opinion. Early assessment can guide decisions about whether or not to continue test development, and ideally to optimize the process. Drug Dev Res 77 : 374-378, 2016. © 2016 Wiley Periodicals, Inc.

  13. Biomarkers in Pediatric ARDS: Future Directions

    Directory of Open Access Journals (Sweden)

    Benjamin E Orwoll


    Full Text Available Acute respiratory distress syndrome (ARDS is common among mechanically ventilated children, and accompanies up to 30% of all PICU deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids such as brochoalveolar lavage have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pediatric ARDS (pARDS provides additional impetus for measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.

  14. Lung cancer biomarkers in exhaled breath. (United States)

    Amann, Anton; Corradi, Massimo; Mazzone, Peter; Mutti, Antonio


    Lung cancer is the leading cause of cancer-related mortality worldwide. Methods for early detection of lung cancer, such as computerized tomography scanning technology, often discover a large number of small lung nodules, posing a new problem to radiologists and chest physicians. The vast majority of these nodules will be benign, but there is currently no easy way to determine which nodules represent very early lung cancer. Adjuvant testing with PET imaging and nonsurgical biopsies has a low yield for these small indeterminate nodules, carries potential morbidity and is costly. Indeed, purely morphological criteria seem to be insufficient for distinguishing lung cancer from benign nodules at early stages with sufficient confidence, therefore false positives undergoing surgical resection frequently occur. A molecular approach to the diagnosis of lung cancer through the analysis of exhaled breath could greatly improve the specificity of imaging procedures. A biomarker-driven approach to signs or symptoms possibly due to lung cancer would represent a complementary tool aimed at ruling out (with known error probability) rather than diagnosing lung cancer. Volatile and nonvolatile components of the breath are being studied as biomarkers of lung cancer. Breath testing is noninvasive and potentially inexpensive. There is promise that an accurate lung cancer breath biomarker, capable of being applied clinically, will be developed in the near future. In this article, we summarize some of the rationale for breath biomarker development, review the published literature in this field and provide thoughts regarding future directions.

  15. Quantitative multiplex detection of pathogen biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Mukundan, Harshini; Xie, Hongzhi; Swanson, Basil I.; Martinez, Jennifer; Grace, Wynne K.


    The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.

  16. Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar


    Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

  17. Pulmonary biomarkers in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Barnes, Peter J.; Chowdhury, Badrul; Kharitonov, Sergei A.; Magnussen, Helgo; Page, Clive P.; Postma, Dirkje; Saetta, Marina


    There has been increasing interest in using pulmonary biomarkers to understand and monitor the inflammation in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD). In this Pulmonary Perspective we discuss the merits of the various approaches by reviewing the current l

  18. Potential Serological Biomarkers of Cerebral Malaria

    Directory of Open Access Journals (Sweden)

    Naomi W. Lucchi


    Full Text Available Biomarkers have been used to diagnose and prognosticate the progress and outcome of many chronic diseases such as neoplastic and non communicable diseases. However, only recently did the field of malaria research move in the direction of actively identifying biomarkers that can accurately discriminate the severe forms of malaria. Malaria continues to be a deadly disease, killing close to a million people (mostly children every year. One life-threatening complication of malaria is cerebral malaria (CM. Studies carried out in Africa have demonstrated that even with the best treatment, as high as 15–30% of CM patients die and about 10–24% of CM survivors suffer short-or long-term neurological impairment. The transition from mild malaria to CM can be sudden and requires immediate intervention. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify CM patients and potential risk for adverse outcomes would greatly enhance better intervention and clinical management to improve the outcomes. We review here what is currently known regarding biomarkers for CM outcomes.

  19. 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)


    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.)

  20. Biomarker Use in Tailored Combat Casualty Care (United States)


    468 Brown, Safford, Caraman ica & Elster In the following sections, we describe our efforts ro define rhe role of biomarkers :moci- ated wich...Salroraf;u GH, Peru ~ G: Principle• of ’"u 12 Bently R, Nuccin P, Wolfe E tr a/.: 250(6), 1002-1007 (2009). M11gcry: cu rrtnt cunccpt~ n nd fn ru rc

  1. Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity. (United States)

    Redman, Christopher W G; Staff, Anne Cathrine


    The maternal syndrome of preeclampsia is mediated by dysfunctional syncytiotrophoblast (STB). When this is stressed by uteroplacental malperfusion, its signaling to the mother changes, as part of a highly coordinated stress response. The STB signals are both proinflammatory and dysangiogenic such that the preeclamptic mother has a stronger vascular inflammatory response than normal, with an antiangiogenic bias. Angiogenic factors have limitations as preeclampsia biomarkers, especially for prediction and diagnosis of preeclampsia at term. However, if they are recognized as markers of STB stress, their physiological changes at term demonstrate that STB stress develops in all pregnancies. The biomarkers reveal that the duration of pregnancies is restricted by placental capacity, such that there is increasing placental dysfunction, at and beyond term. This capacity includes limitations imposed by the size of the uterus, the capacity of the uteroplacental circulation and, possibly, the supply of villous progenitor trophoblast cells. Limited placental capacity explains the increasing risks of postmaturity, including preeclampsia. Early-onset preeclampsia is predictable because STB stress and changes in its biomarkers are intrinsic to poor placentation, an early pregnancy pathology. Prediction of preeclampsia at term is not good because there is no early STB pathology. Moreover, biomarkers cannot accurately diagnose term preeclampsia against a background of universal STB dysfunction, which may or may not be clinically revealed before spontaneous or induced delivery. In this sense, postterm pregnancy is, at best, a pseudonormal state. However, the markers may prove useful in screening for women with more severe problems of postmaturity.


    Directory of Open Access Journals (Sweden)

    Ernest Marshall Graham


    Full Text Available Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the liquid brain biopsy. A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

  3. Biomarkers of necrotising soft tissue infections

    DEFF Research Database (Denmark)

    Hansen, Marco Bo; Simonsen, Ulf; Garred, Peter


    INTRODUCTION: The mortality and amputation rates are still high in patients with necrotising soft tissue infections (NSTIs). It would be ideal to have a set of biomarkers that enables the clinician to identify high-risk patients with NSTI on admission. The objectives of this study are to evaluate...

  4. Quantitative multiplex detection of pathogen biomarkers (United States)

    Mukundan, Harshini; Xie, Hongzhi; Swanson, Basil I; Martinez, Jennifer; Grace, Wynne K


    The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.

  5. Huntington's disease : functional and structural biomarkers

    NARCIS (Netherlands)

    Dumas, Eve Marie


    The aims of this thesis were to gain insight into specific disease processes in Huntington’s Disease (HD) and to identify biomarkers. To achieve these aims, cognitive functioning, structural brain characteristics and intrinstic functional brain connectivity of premanifest and early HD subjects were

  6. Biomarkers in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Sin, Don D; Vestbo, Jørgen


    Currently, with exception of lung function tests, there are no well validated biomarkers or surrogate endpoints that can be used to establish efficacy of novel drugs for chronic obstructive pulmonary disease (COPD). However, the lung function test is not an ideal surrogate for short-term drug...

  7. Cerebrospinal fluid biomarkers for Parkinson's disease

    DEFF Research Database (Denmark)

    Dammann Andersen, Andreas; Binzer, Michael; Stenager, Egon;


    Diagnosticering af Parkinson's sygdom (PD) er baseret på den kliniske udvikling af sygdommen samt en fysisk undersøgelse af patienten, men fejldiagnosticering sker hyppigt; specielt i tidlige stadier. Biomarkører for PD kan muliggøre en tidligere og mere præcis diagnosticering samt monitorering af...

  8. Cerebrospinal fluid biomarker candidates for parkinsonian disorders

    Directory of Open Access Journals (Sweden)

    Radu eConstantinescu


    Full Text Available The parkinsonian disorders are a large group of neurodegenerative diseases including idiopathic Parkinson's disease (PD and atypical parkinsonian disorders, such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The etiology of these disorders is not known although it is considered to be a combination of genetic and environmental factors. One of the greatest obstacles for developing efficacious disease-modifying treatment strategies is the lack of biomarkers. Reliable biomarkers are needed for early and accurate diagnosis, to measure disease progression and response to therapy. In this review several of the most promising cerebrospinal biomarker candidates are discussed. Alpha synuclein seems to be intimately involved in the pathogenesis of synucleinopathies and its levels can be measured in the cerebrospinal fluid and in plasma. In a similar way, tau protein accumulation seems to be involved in the pathogenesis of tauopathies. Urate, a potent antioxidant, seems to be associated to the risk of developing PD and with its progression. Neurofilament light chain levels are increased in atypical parkinsonian disorders compared with PD and healthy controls. The new "omics" techniques are potent tools offering new insights in the patho-etiology of these disorders. Some of the difficulties encountered in developing biomarkers are discussed together with future perspectives.

  9. Biomarkers in Parkinson's disease: Advances and strategies. (United States)

    Delenclos, Marion; Jones, Daryl R; McLean, Pamela J; Uitti, Ryan J


    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1% of the worldwide population. Despite considerable progress in understanding PD pathophysiology, including genetic and biochemical causes, diagnostic approaches lack accuracy and interventions are restricted to symptomatic treatments. PD is a complex syndrome with different clinical subtypes and a wide variability in disorder course. In order to deliver better clinical management of PD patients and discovery of novel therapies, there is an urgent need to find sensitive, specific, and reliable biomarkers. The development of biomarkers will not only help the scientific community to identify populations at risk, but also facilitate clinical diagnosis. Furthermore, these tools could monitor progression, which could ultimately deliver personalized therapeutic strategies. The field of biomarker discovery in PD has attracted significant attention and there have been numerous contributions in recent years. Although none of the parameters have been validated for clinical practice, some candidates hold promise. This review summarizes recent advances in the development of PD biomarkers and discusses new strategies for their utilization.

  10. Biomarkers of fever: from bench to bedside

    NARCIS (Netherlands)

    M. Limper (Maarten)


    markdownabstract__Abstract__ This thesis aims to study biomarkers in inflammation and infection, with a special focus on the distinction between infectious and non-infectious fever. The thesis consists of three parts, part I being this introduction, in which the concept of fever in infectious and n

  11. Novel biomarkers for cancer detection and prognostication

    NARCIS (Netherlands)

    Mehra, N.


    In this thesis we used a variety of approaches for biomarker discovery; in Part I we assessed whether we could identify a non-invasive surrogate markers of angiogenesis, as new vessel formation plays critical roles in the growth and metastatic spread of tumors. Moreover, many agents targeting the va

  12. A Comparative Analysis of Biomarker Selection Techniques

    Directory of Open Access Journals (Sweden)

    Nicoletta Dessì


    Full Text Available Feature selection has become the essential step in biomarker discovery from high-dimensional genomics data. It is recognized that different feature selection techniques may result in different set of biomarkers, that is, different groups of genes highly correlated to a given pathological condition, but few direct comparisons exist which quantify these differences in a systematic way. In this paper, we propose a general methodology for comparing the outcomes of different selection techniques in the context of biomarker discovery. The comparison is carried out along two dimensions: (i measuring the similarity/dissimilarity of selected gene sets; (ii evaluating the implications of these differences in terms of both predictive performance and stability of selected gene sets. As a case study, we considered three benchmarks deriving from DNA microarray experiments and conducted a comparative analysis among eight selection methods, representatives of different classes of feature selection techniques. Our results show that the proposed approach can provide useful insight about the pattern of agreement of biomarker discovery techniques.

  13. Hypermethylated DNA, a Biomarker for colorectal cancer

    DEFF Research Database (Denmark)

    Rasmussen, Simon Ladefoged; Krarup, Henrik Bygum; Sunesen, Kåre Gotschalck;


    and specific for CRC have been proposed. Articles describing the use of hypermethylated promoter regions in blood or stool as biomarkers for CRC were systematically reviewed. METHOD: The Medline, Web of Science, and Embase databases were used in a systematic literature search. Studies were included...


    Many marine eukaryotic algae have been shown to possess characteristic chemotaxonomic lipid biomarkers. Dinoflagellates in particular are often characterized by the presence of sterols and pigments that are rarely found in other classes of algae. To evaluate the utility of chemic...

  15. Developmental neurotoxicity of propylthiouracil in rats

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Hansen, Pernille Reimer; Christiansen, Sofie;


    early in pregnancy may cause adverse effects on the offspring. This has led to increased concern about thyroid hormone disrupting chemicals (TDCs) in our environment. We have studied how developmental exposure to the known antithyroid agent propylthiouracil (PTU) affects the development of rat pups...... behaviour and hearing function. This supports that exposure to TDC's in general may cause long-lasting developmental neurotoxicity....

  16. Developmental Dyspraxia: Is It a Unitary Function? (United States)

    Ayres, A. Jean; And Others


    A group of 182 children (ages four through nine) with known or suspected sensory integrative dysfunction were assessed using tests and clinical observations to examine developmental dyspraxia. The study did not justify the existence of either a unitary function or different types of developmental dyspraxia. (Author/CH)

  17. Static balance and developmental coordination disorder

    NARCIS (Netherlands)

    Geuze, RH


    The development of static balance is a basic characteristic of normal motor development. Most of the developmental motor tests include a measure of static balance. Children with a developmental coordination disorder (DCD) often fail this item. Twenty-four children at risk for DCD with balance proble

  18. Essential Role of Culture in Developmental Psychology (United States)

    Miller, Joan G.


    This chapter argues for the essential role of culture in forming the basic constructs and theories of developmental psychology. The case is made for the need to overcome the cultural insularity of core developmental concepts and methods in order to create a psychology that is more truly universal.

  19. 48 CFR 919.7011 - Developmental assistance. (United States)


    ... PROGRAMS SMALL BUSINESS PROGRAMS The Department of Energy Mentor-Protege Program 919.7011 Developmental assistance. (a) The forms of developmental assistance a Mentor may provide to a Protege include, but are not... leased by Mentor; and (7) Temporary assignment of Mentor personnel to the Protege for purposes...

  20. Exploring Best Practices in Developmental Math (United States)

    Cafarella, Brian V.


    Currently, many community colleges are struggling with poor student success rates in developmental math. Therefore, this qualitative study focused on employing best practices in developmental mathematics at an urban community college in Dayton, Ohio. Guiding the study were the following research questions: What are the best practices utilized by a…

  1. Innovative Developmental Education Programs: A Texas Model (United States)

    Booth, Eric A.; Capraro, Mary Margaret; Capraro, Robert M.; Chaudhuri, Nandita; Dyer, James; Marchbanks, Miner P., III


    This article provides insights from a 2-year, cross-site evaluation of state funded developmental education sites and serves as a focus article for response by those sites. Receiving grants from the Texas Higher Education Coordinating Board (THECB), nine sites (5 community colleges and 4 universities) implemented innovative developmental education…

  2. Developmental Critical Thinking: Melding Two Imperatives. (United States)

    Harris, Jimmy Carl; Eleser, Chris


    Describes the genesis of a developmental critical-thinking course offered at Southeastern Louisiana University (SLU) that melds two imperatives: to provide a comprehensive developmental-education program and to satisfy the critical-thinking requirements of the job market and the university. Provides some preliminary evaluation results from faculty…

  3. Developmental Assessment. Assessment Resource Kit(ARK). (United States)

    Masters, Geoff; Forster, Margaret

    Developmental assessment is the process of monitoring a student's progress through an area of learning so that decisions can be made about the best way to facilitate further learning. The unique feature of developmental assessment is its use of a progress map. The progress map, or continuum, describes the development in an area of learning and so…

  4. Psychological Resources of Adults with Developmental Dyslexia (United States)

    Lockiewicz, Marta; Bogdanowicz, Katarzyna M.; Bogdanowicz, Marta


    The aim of our study was to describe specific psychological resources of adults with developmental dyslexia and compare them with psychological resources of adults without developmental dyslexia. Potential differences were analyzed in visual-spatial, creative, and motivational abilities. No evidence was found for either creative, or visuospatial…

  5. A Taxometric Investigation of Developmental Dyslexia Subtypes (United States)

    O'Brien, Beth A.; Wolf, Maryanne; Lovett, Maureen W.


    Long-standing issues with the conceptualization, identification and subtyping of developmental dyslexia persist. This study takes an alternative approach to examine the heterogeneity of developmental dyslexia using taxometric classification techniques. These methods were used with a large sample of 671 children ages 6-8 who were diagnosed with…

  6. Developmentally Appropriate Practice: Myths and Facts. (United States)

    Galen, Harlene


    Debunks various myths and misperceptions concerning developmentally appropriate practices. Developmental appropriateness is a philosophy, not a curriculum. Despite using alternative learning strategies such as guided play, teachers are in control, facilitate real academic learning, and build on what they already know. DAP is universal and can…

  7. State of the States in Developmental Disabilities (United States)

    Braddock, David; Hemp, Richard; Rizzolo, Mary Kay


    This is the latest edition of the "State of the States in Developmental Disabilities" study--a thorough and the only one of its kind investigation on public spending, revenues, and programmatic trends of intellectual and developmental programs and services within the United States since 1977. Directed by leading researcher, Dr. David Braddock, the…

  8. Developmental Cognitive Neuroscience: Origins, Issues, and Prospects (United States)

    Pennington, Bruce F.; Snyder, Kelly A.; Roberts, Ralph J., Jr.


    This commentary explains how the field of developmental cognitive neuroscience (DCN) holds the promise of a much wider interdisciplinary integration across sciences concerned with development: psychology, molecular genetics, neurobiology, and evolutionary developmental biology. First we present a brief history of DCN, including the key theoretical…

  9. Developmental spinal canal stenosis and somatotype.


    Nightingale, S.


    The hypothesis that somatotype and cervical spine developmental canal stenosis may be associated has been investigated by anthropometry and measurement of lateral projection cervical spine radiographs. A significant association of canal size with somatotype has been found such that those with developmentally narrow canals are more likely to have relatively shorter long-bones, particularly in the upper arm, and longer trunks.

  10. Toward a Developmental Operational Definition of Autism. (United States)

    Gillham, Jane E.; Carter, Alice S.; Volkmar, Fred R.; Sparrow, Sara S.


    Vineland Adaptive Behavior Scales scores and measures of intellectual functioning obtained for 44 children (ages 4-13) with autism, 21 with pervasive developmental disorder not otherwise specified, and 30 with developmental disorders, indicated autism and combined nonautism groups could be differentiated on socialization, daily living skills, and…

  11. Developmental Psychopathology: Pathways to the Future (United States)

    Masten, Ann S.


    This article highlights the defining principles, progress and future directions in developmental psychopathology in relation to this special section. Six fundamental principles of developmental psychopathology are identified and the pervasive impact of this integrative framework on research, theory, and practice in behavioral health fields over…

  12. Piaget's Enduring Contribution to Developmental Psychology. (United States)

    Beilin, Harry


    Describes Jean Piaget's transformation of society's conception of childhood thought. Emphasizes the enduring contribution to developmental psychology of Piaget's constructivism, his description of developmental mechanisms, his cognitivism, his explication of structural and functional analysis, and his addressing of epistemological issues and…

  13. South Africa's "Developmental State" Distraction

    Directory of Open Access Journals (Sweden)

    Patrick Bond


    Full Text Available The idea that the South African ruling elite has the political will to establish a “developmental state” project early in the 21st century is popular, but is not borne out by evidence thus far. Patrick Bond reviews new information about the neoliberal project’s failures, which range from macroeconomics to microdevelopment to pro-corporate megaprojects, and which are accompanied by a tokenistic welfare policy not designed to provide sufficient sustenance or entitlements to the society. The critique by the independent left might be revised in the event that the trade unions and communist influences within the ruling Alliance strengthen, but there is a greater likelihood that the world capitalist crisis will have the opposite impact. Nevertheless, widespread grassroots protests and impressive campaigning by civil society keep alive the hope for a post-capitalist, post-nationalist politics, as bandaiding South African capitalism runs into trouble.

  14. Developmental hip dysplasia in adolescence

    Directory of Open Access Journals (Sweden)

    Vukašinović Zoran


    Full Text Available The authors define adolescence and developmental dysplasia of the hip (DDH. Special attention is paid to pathological findings characteristic of DDH in adolescence (unrecognized and untreated DDH; treated DDH, but non-terminated treatment; DDH diagnosed with delay, inadequately treated, with complications. The authors emphasise that DDH treatment has to be successfully terminated well before the adolescence; possibilities are explained on management modes at the time of adolescence, and possible persons guilty for the persistence of later hip problems are indicated. Based on the authors' experience and having in mind all surgical possibilities for the treatment (pelvic osteotomies, femoral osteotomies, trochanteroplasties, leg length equalization procedures the authors propose treatment protocols. The intention is to provide better treatment results and to prevent secondary hip arthrosis. Furthermore, how to improve the struggle against DDH is suggested.

  15. Transgenic mice in developmental toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Woychik, R.P.


    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  16. Transgenic mice in developmental toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Woychik, R.P.


    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  17. Dyslexia: a developmental language disorder. (United States)

    Simpson, S


    The acquisition of literacy in an alphabetic script such as English makes heavy demands on linguistic skills. The relation between spoken and written language however, is far from straightforward. This article reviews the research that suggests that phonological processing skills are crucial in the translation of symbols to sounds, and the development of rapid and automatic decoding skills. It examines research that indicates that children whose phonological processing skills are compromised in some way, are at-risk of experiencing difficulties in the acquisition of literacy; it supports the suggestion that dyslexia can be viewed as lying on the continuum of developmental language disorders. It goes on to relate theory to practice and discusses the responsibilities of health care professionals in relation to the early identification of dyslexia, and makes suggestions regarding intervention. In particular, it looks at the responsibilities of speech and language therapy services in the care and management of children with dyslexia.

  18. Reference interval determination for anabasine: a biomarker of active tobacco use. (United States)

    Suh-Lailam, Brenda B; Haglock-Adler, Carrie J; Carlisle, Heidi J; Ohman, Trent; McMillin, Gwendolyn A


    Laboratory detection of nicotine exposure is important for establishing eligibility for organ transplant and elective surgery. Nicotine testing is also used to verify compliance with nicotine replacement therapies (NRT), smoking cessation programs and for life insurance purposes. Nicotine metabolites, such as cotinine and trans-3'-hydroxycotinine, are used as biomarkers of nicotine exposure. For some clinical applications, it is important to distinguish between active use of tobacco products versus NRT. Anabasine is a tobacco alkaloid that has been used as a biomarker of active tobacco use. However, the use of anabasine as an insecticide, and its presence in consumables other than nicotine products, suggests that anabasine may not be specific to tobacco use/exposure. Here, we determine the reference interval for anabasine in the urine of nonsmokers and compare it to the range of anabasine concentrations observed in the presence or absence of nicotine metabolites.

  19. Current and future trends in biomarker discovery and development of companion diagnostics for arthritis. (United States)

    Gibson, David S; Bustard, Michael J; McGeough, Cathy M; Murray, Helena A; Crockard, Martin A; McDowell, Andrew; Blayney, Jayne K; Gardiner, Philip V; Bjourson, Anthony J


    Musculoskeletal diseases such as rheumatoid arthritis are complex multifactorial disorders that are chronic in nature and debilitating for patients. A number of drug families are available to clinicians to manage these disorders but few tests exist to target these to the most responsive patients. As a consequence, drug failure and switching to drugs with alternate modes of action is common. In parallel, a limited number of laboratory tests are available which measure biological indicators or 'biomarkers' of disease activity, autoimmune status, or joint damage. There is a growing awareness that assimilating the fields of drug selection and diagnostic tests into 'companion diagnostics' could greatly advance disease management and improve outcomes for patients. This review aims to highlight: the current applications of biomarkers in rheumatology with particular focus on companion diagnostics; developments in the fields of proteomics, genomics, microbiomics, imaging and bioinformatics and how integration of these technologies into clinical practice could support therapeutic decisions.

  20. Crowding, reading, and developmental dyslexia. (United States)

    Martelli, Marialuisa; Di Filippo, Gloria; Spinelli, Donatella; Zoccolotti, Pierluigi


    We tested the hypothesis that crowding effects are responsible for the reading slowness characteristic of developmental dyslexia. A total of twenty-nine Italian dyslexics and thirty-three age-matched controls participated in various parts of the study. In Experiment 1, we measured contrast thresholds for identifying letters and words as a function of stimulus duration. Thresholds were higher in dyslexics than controls for words (at a limited time exposure) but not for single letters. Adding noise to the stimuli produced comparable effects in dyslexics and controls. At the long time exposure thresholds were comparable in the two groups. In Experiment 2, we measured the spacing between a target letter and two flankers at a fixed level of performance as a function of eccentricity and size. With eccentricity, the critical spacing (CS) scaled in the control group with 0.62 proportionality (a value of b close to Bouma's law, 0.50) and with a greater proportionality (0.95) in the dyslexic group. CS was independent of size in both groups. In Experiment 3, we examined the critical print size (CPS), that is, the increase in reading rate up to a critical character size (S. T. Chung, J. S. Mansfield, & G. E. Legge, 1998). CPS of dyslexic children was greater than that of controls. Individual maximal reading speed was predicted by individual bs (from Experiment 2). The maximal reading rate achieved by dyslexics at CPS (and also for larger print sizes) was below the values observed in controls. We conclude that word analysis in dyslexics is slowed because of greater crowding effects, which limit letter identification in multi-letter arrays across the visual field. We propose that the peripheral reading of normal readers might constitute a model for dyslexic reading. The periphery model accounts for 60% of dyslexics' slowness. After compensating for crowding, the dyslexics' reading rate remains slower than that of proficient readers. This failure is discussed in terms of a