WorldWideScience

Sample records for translational safety biomarker

  1. Translational safety biomarkers of colonic barrier integrity in the rat.

    Science.gov (United States)

    Erkens, Tim; Bueters, Ruud; van Heerden, Marjolein; Cuyckens, Filip; Vreeken, Rob; Goeminne, Nick; Lammens, Lieve

    2018-05-20

    The intestinal barrier controls intestinal permeability, and its disruption has been associated with multiple diseases. Therefore, preclinical safety biomarkers monitoring barrier integrity are essential during the development of drugs targeting the intestines, particularly if starting treatment early after onset of disease. Classical toxicology endpoints are not sensitive enough and therefore our objective was to identify non-invasive markers enabling early in vivo detection of colonic barrier perturbation. Male Sprague-Dawley rats were dosed intracolonically via the rectum, using sodium caprate or ibuprofen as tool compounds to alter barrier integrity. Several potentially translational biomarkers and probe molecules related to permeability, inflammation or tissue damage were evaluated, using various analytical platforms, including immunoassays, targeted metabolomics and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry. Several markers were identified that allow early in vivo detection of colonic barrier integrity changes, before histopathological evidence of tissue damage. The most promising permeability markers identified were plasma fluorescein isothiocyanate-dextran 4000 and a lactulose/mannitol/sucralose mixture in urine. These markers showed maximum increases over 100-fold or approximately 10-50-fold, respectively. Intracolonic administration of the above probe molecules outperformed oral administration and inflammatory or other biomarkers, such as α 2 -macroglobulin, calprotectin, cytokines, prostaglandins and a panel of metabolic molecules to identify early and subtle changes in barrier integrity. However, optimal timing of probe administration and sample collection is important for all markers evaluated. Inclusion of these probe molecules in preclinical toxicity studies might aid in risk assessment and the design of a clinical biomarker plan, as several of these markers have translational potential. Copyright © 2018 John

  2. Impact of biomarker development on drug safety assessment

    International Nuclear Information System (INIS)

    Marrer, Estelle; Dieterle, Frank

    2010-01-01

    Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

  3. UCLA Translational Biomarker Development Program (UTBD)

    Energy Technology Data Exchange (ETDEWEB)

    Czernin, Johannes [Univ. of California, Los Angeles, CA (United States)

    2014-09-01

    The proposed UTBD program integrates the sciences of diagnostic nuclear medicine and (radio)chemistry with tumor biology and drug development. UTBD aims to translate new PET biomarkers for personalized medicine and to provide examples for the use of PET to determine pharmacokinetic (PK) and pharmacodynamic (PD) drug properties. The program builds on an existing partnership between the Ahmanson Translational Imaging Division (ATID) and the Crump Institute of Molecular Imaging (CIMI), the UCLA Department of Chemistry and the Division of Surgical Oncology. ATID provides the nuclear medicine training program, clinical and preclinical PET/CT scanners, biochemistry and biology labs for probe and drug development, radiochemistry labs, and two cyclotrons. CIMI provides DOE and NIH-funded training programs for radio-synthesis (START) and molecular imaging (SOMI). Other participating entities at UCLA are the Department of Chemistry and Biochemistry and the Division of Surgical Oncology. The first UTBD project focuses on deoxycytidine kinase, a rate-limiting enzyme in nucleotide metabolism, which is expressed in many cancers. Deoxycytidine kinase (dCK) positive tumors can be targeted uniquely by two distinct therapies: 1) nucleoside analog prodrugs such as gemcitabine (GEM) are activated by dCK to cytotoxic antimetabolites; 2) recently developed small molecule dCK inhibitors kill tumor cells by starving them of nucleotides required for DNA replication and repair. Since dCK-specific PET probes are now available, PET imaging of tumor dCK activity could improve the use of two different classes of drugs in a wide variety of cancers.

  4. PODCAST: From Lost in Translation to Paradise Found: Enabling Protein Biomarker Method Transfer by Mass Spectrometry | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Translation of novel biomarkers into clinical care for the evaluation of therapeutic safety and efficacy has been slow, partly attributable to the cost and complexity of immunoassay development.  The potential for liquid chromatography-tandem mass spectrometry (LC-MS/MS) to streamline the translation of novel protein biomarkers is profound.  Drs. Henry Rodriguez and Andrew Hoofnagle discuss what the future may be for clinical proteomics. This is an American Association for Clinical Chemistry (AACC) podcast.

  5. Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

    Science.gov (United States)

    Hainfellner, J A; Heinzl, H

    2010-01-01

    Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.

  6. Nonclinical safety biomarkers of drug-induced vascular injury: current status and blueprint for the future.

    Science.gov (United States)

    Mikaelian, Igor; Cameron, Mark; Dalmas, Deidre A; Enerson, Bradley E; Gonzalez, Raymond J; Guionaud, Silvia; Hoffmann, Peter K; King, Nicholas M P; Lawton, Michael P; Scicchitano, Marshall S; Smith, Holly W; Thomas, Roberta A; Weaver, James L; Zabka, Tanja S

    2014-06-01

    Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. © 2014 by The Author(s).

  7. Translating Health Services Research into Practice in the Safety Net.

    Science.gov (United States)

    Moore, Susan L; Fischer, Ilana; Havranek, Edward P

    2016-02-01

    To summarize research relating to health services research translation in the safety net through analysis of the literature and case study of a safety net system. Literature review and key informant interviews at an integrated safety net hospital. This paper describes the results of a comprehensive literature review of translational science literature as applied to health care paired with qualitative analysis of five key informant interviews conducted with senior-level management at Denver Health and Hospital Authority. Results from the literature suggest that implementing innovation may be more difficult in the safety net due to multiple factors, including financial and organizational constraints. Results from key informant interviews confirmed the reality of financial barriers to innovation implementation but also implied that factors, including institutional respect for data, organizational attitudes, and leadership support, could compensate for disadvantages. Translating research into practice is of critical importance to safety net providers, which are under increased pressure to improve patient care and satisfaction. Results suggest that translational research done in the safety net can better illuminate the special challenges of this setting; more such research is needed. © Health Research and Educational Trust.

  8. Nuclear Criticality Safety Handbook, Version 2. English translation

    International Nuclear Information System (INIS)

    2001-08-01

    The Nuclear Criticality Safety Handbook, Version 2 essentially includes the description of the Supplement Report to the Nuclear Criticality Safety Handbook, released in 1995, into the first version of the Nuclear Criticality Safety Handbook, published in 1988. The following two points are new: (1) exemplifying safety margins related to modeled dissolution and extraction processes, (2) describing evaluation methods and alarm system for criticality accidents. Revision has been made based on previous studies for the chapter that treats modeling the fuel system: e.g., the fuel grain size that the system can be regarded as homogeneous, non-uniformity effect of fuel solution, an burnup credit. This revision has solved the inconsistencies found in the first version between the evaluation of errors found in JACS code system and the criticality condition data that were calculated based on the evaluation. This report is an English translation of the Nuclear Criticality Safety Handbook, Version 2, originally published in Japanese as JAERI 1340 in 1999. (author)

  9. The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity

    International Nuclear Information System (INIS)

    Amacher, David E.

    2010-01-01

    Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in

  10. Knowledge Translation and Patient Safety: The Canadian Adverse Events Study

    OpenAIRE

    Baker, G. Ross; Norton, Peter; Flintoft, Virginia

    2006-01-01

    The Canadian Adverse Events Study was the first national study of adverse events in Canadian hospitals. Learning from the controversy surrounding similar studies in other countries, the team engaged in extensive knowledge translation activities throughout the life of the project. Using meetings, Web-based communication and other tools, the team successfully prepared most Canadian stakeholders for the study’s release, allowing them to develop anticipatory patient safety initiatives. However, u...

  11. Bio-markers: traceability in food safety issues.

    Science.gov (United States)

    Raspor, Peter

    2005-01-01

    Research and practice are focusing on development, validation and harmonization of technologies and methodologies to ensure complete traceability process throughout the food chain. The main goals are: scale-up, implementation and validation of methods in whole food chains, assurance of authenticity, validity of labelling and application of HACCP (hazard analysis and critical control point) to the entire food chain. The current review is to sum the scientific and technological basis for ensuring complete traceability. Tracing and tracking (traceability) of foods are complex processes due to the (bio)markers, technical solutions and different circumstances in different technologies which produces various foods (processed, semi-processed, or raw). Since the food is produced for human or animal consumption we need suitable markers to be stable and traceable all along the production chain. Specific biomarkers can have a function in technology and in nutrition. Such approach would make this development faster and more comprehensive and would make possible that food effect could be monitored with same set of biomarkers in consumer. This would help to develop and implement food safety standards that would be based on real physiological function of particular food component.

  12. Sociology, systems and (patient) safety: knowledge translations in healthcare policy.

    Science.gov (United States)

    Jensen, Casper Bruun

    2008-03-01

    In 2000 the American Institute of Medicine, adviser to the federal government on policy matters relating to the health of the public, published the report To Err is Human: Building a Safer Health System, which was to become a call to arms for improving patient safety across the Western world. By re-conceiving healthcare as a system, it was argued that it was possible to transform the current culture of blame, which made individuals take defensive precautions against being assigned responsibility for error - notably by not reporting adverse events, into a culture of safety. The IOM report draws on several prominent social scientists in accomplishing this re-conceptualisation. But the analyses of these authors are not immediately relevant for health policy. It requires knowledge translation to make them so. This paper analyses the process of translation. The discussion is especially pertinent due to a certain looping effect between social science research and policy concerns. The case here presented is thus doubly illustrative: exemplifying first how social science is translated into health policy and secondly how the transformation required for this to function is taken as an analytical improvement that can in turn be redeployed in social research.

  13. In Vivo Imaging Biomarkers in Mouse Models of Alzheimer's Disease: Are We Lost in Translation or Breaking Through?

    Directory of Open Access Journals (Sweden)

    Benoît Delatour

    2010-01-01

    Full Text Available Identification of biomarkers of Alzheimer's Disease (AD is a critical priority to efficiently diagnose the patients, to stage the progression of neurodegeneration in living subjects, and to assess the effects of disease-modifier treatments. This paper addresses the development and usefulness of preclinical neuroimaging biomarkers of AD. It is today possible to image in vivo the brain of small rodents at high resolution and to detect the occurrence of macroscopic/microscopic lesions in these species, as well as of functional alterations reminiscent of AD pathology. We will outline three different types of imaging biomarkers that can be used in AD mouse models: biomarkers with clear translational potential, biomarkers that can serve as in vivo readouts (in particular in the context of drug discovery exclusively for preclinical research, and finally biomarkers that constitute new tools for fundamental research on AD physiopathogeny.

  14. Diagnostic Biomarkers for Posttraumatic Stress Disorder (PTSD): Promising Horizons from Translational Neuroscience Research

    Science.gov (United States)

    Michopoulos, Vasiliki; Norrholm, Seth Davin; Jovanovic, Tanja

    2015-01-01

    Posttraumatic stress disorder (PTSD) is a heterogeneous disorder that affects individuals exposed to trauma (e.g., combat, interpersonal violence, and natural disasters). Although its diagnostic features have been recently re-classified with the emergence of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5), the disorder remains characterized by hyperarousal, intrusive reminders of the trauma, avoidance of trauma-related cues, and negative cognition and mood. This heterogeneity indicates the presence of multiple neurobiological mechanisms underlying the etiology and maintenance of PTSD. Translational research spanning the past few decades has revealed several potential avenues for the identification of diagnostic biomarkers for PTSD. These include, but are not limited to, monoaminergic transmitter systems, the hypothalamic-pituitary-adrenal (HPA) axis, metabolic hormonal pathways, inflammatory mechanisms, psychophysiological reactivity, and neural circuits. The current review provides an update to the literature with regard to the most promising putative PTSD biomarkers with specific emphasis on the interaction between neurobiological influences on disease risk and symptom progression. Such biomarkers will most likely be identified by multi-dimensional models derived from comprehensive descriptions of molecular, neurobiological, behavioral, and clinical phenotypes. PMID:25727177

  15. Diagnostic Biomarkers for Posttraumatic Stress Disorder: Promising Horizons from Translational Neuroscience Research.

    Science.gov (United States)

    Michopoulos, Vasiliki; Norrholm, Seth Davin; Jovanovic, Tanja

    2015-09-01

    Posttraumatic stress disorder (PTSD) is a heterogeneous disorder that affects individuals exposed to trauma (e.g., combat, interpersonal violence, and natural disasters). Although its diagnostic features have been recently reclassified with the emergence of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition, the disorder remains characterized by hyperarousal, intrusive reminders of the trauma, avoidance of trauma-related cues, and negative cognition and mood. This heterogeneity indicates the presence of multiple neurobiological mechanisms underlying the etiology and maintenance of PTSD. Translational research spanning the past few decades has revealed several potential avenues for the identification of diagnostic biomarkers for PTSD. These include, but are not limited to, monoaminergic transmitter systems, the hypothalamic-pituitary-adrenal axis, metabolic hormonal pathways, inflammatory mechanisms, psychophysiological reactivity, and neural circuits. The current review provides an update to the literature with regard to the most promising putative PTSD biomarkers, with specific emphasis on the interaction between neurobiological influences on disease risk and symptom progression. Such biomarkers will most likely be identified by multi-dimensional models derived from comprehensive descriptions of molecular, neurobiological, behavioral, and clinical phenotypes. Copyright © 2015 Society of Biological Psychiatry. All rights reserved.

  16. Biomarkers of a five-domain translational substrate for schizophrenia and schizoaffective psychosis.

    Science.gov (United States)

    Fryar-Williams, Stephanie; Strobel, Jörg E

    2015-01-01

    The Mental Health Biomarker Project (2010-2014) selected commercial biochemistry markers related to monoamine synthesis and metabolism and measures of visual and auditory processing performance. Within a case-control discovery design with exclusion criteria designed to produce a highly characterised sample, results from 67 independently DSM IV-R-diagnosed cases of schizophrenia and schizoaffective disorder were compared with those from 67 control participants selected from a local hospital, clinic and community catchment area. Participants underwent protocol-based diagnostic-checking, functional-rating, biological sample-collection for thirty candidate markers and sensory-processing assessment. Fifteen biomarkers were identified on ROC analysis. Using these biomarkers, odds ratios, adjusted for a case-control design, indicated that schizophrenia and schizoaffective disorder were highly associated with dichotic listening disorder, delayed visual processing, low visual span, delayed auditory speed of processing, low reverse digit span as a measure of auditory working memory and elevated levels of catecholamines. Other nutritional and biochemical biomarkers were identified as elevated hydroxyl pyrroline-2-one as a marker of oxidative stress, vitamin D, B6 and folate deficits with elevation of serum B12 and free serum copper to zinc ratio. When individual biomarkers were ranked by odds ratio and correlated with clinical severity, five functional domains of visual processing, auditory processing, oxidative stress, catecholamines and nutritional-biochemical variables were formed. When the strengths of their inter-domain relationships were predicted by Lowess (non-parametric) regression, predominant bidirectional relationships were found between visual processing and catecholamine domains. At a cellular level, the nutritional-biochemical domain exerted a pervasive influence on the auditory domain as well as on all other domains. The findings of this biomarker research

  17. Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms.

    Science.gov (United States)

    Le-Niculescu, H; Balaraman, Y; Patel, S D; Ayalew, M; Gupta, J; Kuczenski, R; Shekhar, A; Schork, N; Geyer, M A; Niculescu, A B

    2011-05-24

    Anxiety disorders are prevalent and disabling yet understudied from a genetic standpoint, compared with other major psychiatric disorders such as bipolar disorder and schizophrenia. The fact that they are more common, diverse and perceived as embedded in normal life may explain this relative oversight. In addition, as for other psychiatric disorders, there are technical challenges related to the identification and validation of candidate genes and peripheral biomarkers. Human studies, particularly genetic ones, are susceptible to the issue of being underpowered, because of genetic heterogeneity, the effect of variable environmental exposure on gene expression, and difficulty of accrual of large, well phenotyped cohorts. Animal model gene expression studies, in a genetically homogeneous and experimentally tractable setting, can avoid artifacts and provide sensitivity of detection. Subsequent translational integration of the animal model datasets with human genetic and gene expression datasets can ensure cross-validatory power and specificity for illness. We have used a pharmacogenomic mouse model (involving treatments with an anxiogenic drug--yohimbine, and an anti-anxiety drug--diazepam) as a discovery engine for identification of anxiety candidate genes as well as potential blood biomarkers. Gene expression changes in key brain regions for anxiety (prefrontal cortex, amygdala and hippocampus) and blood were analyzed using a convergent functional genomics (CFG) approach, which integrates our new data with published human and animal model data, as a translational strategy of cross-matching and prioritizing findings. Our work identifies top candidate genes (such as FOS, GABBR1, NR4A2, DRD1, ADORA2A, QKI, RGS2, PTGDS, HSPA1B, DYNLL2, CCKBR and DBP), brain-blood biomarkers (such as FOS, QKI and HSPA1B), pathways (such as cAMP signaling) and mechanisms for anxiety disorders--notably signal transduction and reactivity to environment, with a prominent role for the

  18. Identification of Novel Translational Urinary Biomarkers for Acetaminophen-Induced Acute Liver Injury Using Proteomic Profiling in Mice

    NARCIS (Netherlands)

    van Swelm, Rachel P. L.; Laarakkers, Coby M. M.; van der Kuur, Ellen C.; Morava-Kozicz, Eva; Wevers, Ron A.; Augustijn, Kevin D.; Touw, Daan J.; Sandel, Maro H.; Masereeuw, Rosalinde; Russel, Frans G. M.

    2012-01-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced

  19. Post-translationally modified muscle-specific ubiquitin ligases as circulating biomarkers in experimental cancer cachexia

    Science.gov (United States)

    Mota, Roberto; Rodríguez, Jessica E; Bonetto, Andrea; O’Connell, Thomas M; Asher, Scott A; Parry, Traci L; Lockyer, Pamela; McCudden, Christopher R; Couch, Marion E; Willis, Monte S

    2017-01-01

    Cancer cachexia is a severe wasting syndrome characterized by the progressive loss of lean body mass and systemic inflammation. Up to 80% of cancer patients experience cachexia, with 20-30% of cancer-related deaths directly linked to cachexia. Despite efforts to identify early cachexia and cancer relapse, clinically useful markers are lacking. Recently, we identified the role of muscle-specific ubiquitin ligases Atrogin-1 (MAFbx, FBXO32) and Muscle Ring Finger-1 in the pathogenesis of cardiac atrophy and hypertrophy. We hypothesized that during cachexia, the Atrogin-1 and MuRF1 ubiquitin ligases are released from muscle and migrate to the circulation where they could be detected and serve as a cachexia biomarker. To test this, we induced cachexia in mice using the C26 adenocarcinoma cells or vehicle (control). Body weight, tumor volume, and food consumption were measured from inoculation until ~day 14 to document cachexia. Western blot analysis of serum identified the presence of Atrogin-1 and MuRF1 with unique post-translational modifications consistent with mono- and poly- ubiquitination of Atrogin-1 and MuRF1 found only in cachectic serum. These findings suggest that both increased Atrogin-1 and the presence of unique post-translational modifications may serve as a surrogate marker specific for cachexia. PMID:28979816

  20. Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach.

    Science.gov (United States)

    Garner, Joseph P; Thogerson, Collette M; Dufour, Brett D; Würbel, Hanno; Murray, James D; Mench, Joy A

    2011-06-01

    The NIMH's new strategic plan, with its emphasis on the "4P's" (Prediction, Pre-emption, Personalization, and Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly specific model of a single disorder by matching this 'fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Cardiac troponins--Translational biomarkers in cardiology: Theory and practice of cardiac troponin high-sensitivity assays.

    Science.gov (United States)

    Adamcova, Michaela; Popelova-Lencova, Olga; Jirkovsky, Eduard; Simko, Fedor; Gersl, Vladimir; Sterba, Martin

    2016-01-01

    Tn is a unique translational biomarker in cardiology whose potential has not been diminished in the new era of high sensitive assays. cTns can be valuable markers in cardiac diseases as well as in infectious diseases and respiratory diseases. Furthermore, the role of cTns is growing in the routine evaluation of cardioxicity and in determining the efficacy/safety ratio of novel cardioprotective strategies in clinical settings. cTns can detect myocardial injury not only in a wide spectrum of laboratory animals in experimental studies in vivo, but also in isolated heart models or cardiomyocytes in vitro. The crucial issue regarding the cross-species usage of cardiac troponin investigation remains the choice of cardiac troponin testing. This review summarizes the recent proteomic data on aminoacid sequences of cTnT and cTnI in various species, as well as selected analytical characteristics of human cardiac troponin high-sensitivity assays. Due to the highly phylogenetically conserved structure of troponins, the same bioindicator can be investigated using the same method in both clinical and experimental cardiology, thus contributing to a better understanding of the pathogenesis of cardiac diseases as well as to increased effectiveness of troponin use in clinical practice. Measuring cardiac troponins using commercially available human high-sensitivity cardiac troponin tests with convenient antibodies selected on the basis of adequate proteomic knowledge can solve many issues which would otherwise be difficult to address in clinical settings for various ethical and practical reasons. Our survey could help elaborate the practical guidelines for optimizing the choice of cTns assay in cardiology. © 2016 International Union of Biochemistry and Molecular Biology.

  2. Crowdsourcing for translational research: analysis of biomarker expression using cancer microarrays.

    Science.gov (United States)

    Lawson, Jonathan; Robinson-Vyas, Rupesh J; McQuillan, Janette P; Paterson, Andy; Christie, Sarah; Kidza-Griffiths, Matthew; McDuffus, Leigh-Anne; Moutasim, Karwan A; Shaw, Emily C; Kiltie, Anne E; Howat, William J; Hanby, Andrew M; Thomas, Gareth J; Smittenaar, Peter

    2017-01-17

    Academic pathology suffers from an acute and growing lack of workforce resource. This especially impacts on translational elements of clinical trials, which can require detailed analysis of thousands of tissue samples. We tested whether crowdsourcing - enlisting help from the public - is a sufficiently accurate method to score such samples. We developed a novel online interface to train and test lay participants on cancer detection and immunohistochemistry scoring in tissue microarrays. Lay participants initially performed cancer detection on lung cancer images stained for CD8, and we measured how extending a basic tutorial by annotated example images and feedback-based training affected cancer detection accuracy. We then applied this tutorial to additional cancer types and immunohistochemistry markers - bladder/ki67, lung/EGFR, and oesophageal/CD8 - to establish accuracy compared with experts. Using this optimised tutorial, we then tested lay participants' accuracy on immunohistochemistry scoring of lung/EGFR and bladder/p53 samples. We observed that for cancer detection, annotated example images and feedback-based training both improved accuracy compared with a basic tutorial only. Using this optimised tutorial, we demonstrate highly accurate (>0.90 area under curve) detection of cancer in samples stained with nuclear, cytoplasmic and membrane cell markers. We also observed high Spearman correlations between lay participants and experts for immunohistochemistry scoring (0.91 (0.78, 0.96) and 0.97 (0.91, 0.99) for lung/EGFR and bladder/p53 samples, respectively). These results establish crowdsourcing as a promising method to screen large data sets for biomarkers in cancer pathology research across a range of cancers and immunohistochemical stains.

  3. Translational database selection and multiplexed sequence capture for up front filtering of reliable breast cancer biomarker candidates.

    Directory of Open Access Journals (Sweden)

    Patrik L Ståhl

    Full Text Available Biomarker identification is of utmost importance for the development of novel diagnostics and therapeutics. Here we make use of a translational database selection strategy, utilizing data from the Human Protein Atlas (HPA on differentially expressed protein patterns in healthy and breast cancer tissues as a means to filter out potential biomarkers for underlying genetic causatives of the disease. DNA was isolated from ten breast cancer biopsies, and the protein coding and flanking non-coding genomic regions corresponding to the selected proteins were extracted in a multiplexed format from the samples using a single DNA sequence capture array. Deep sequencing revealed an even enrichment of the multiplexed samples and a great variation of genetic alterations in the tumors of the sampled individuals. Benefiting from the upstream filtering method, the final set of biomarker candidates could be completely verified through bidirectional Sanger sequencing, revealing a 40 percent false positive rate despite high read coverage. Of the variants encountered in translated regions, nine novel non-synonymous variations were identified and verified, two of which were present in more than one of the ten tumor samples.

  4. Patterns of patient safety culture: a complexity and arts-informed project of knowledge translation.

    Science.gov (United States)

    Mitchell, Gail J; Tregunno, Deborah; Gray, Julia; Ginsberg, Liane

    2011-01-01

    The purpose of this paper is to describe patterns of patient safety culture that emerged from an innovative collaboration among health services researchers and fine arts colleagues. The group engaged in an arts-informed knowledge translation project to produce a dramatic expression of patient safety culture research for inclusion in a symposium. Scholars have called for a deeper understanding of the complex interrelationships among structure, process and outcomes relating to patient safety. Four patterns of patient safety culture--blinding familiarity, unyielding determination, illusion of control and dismissive urgency--are described with respect to how they informed creation of an arts-informed project for knowledge translation.

  5. Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy.

    Science.gov (United States)

    Galindo, Cristi L; Soslow, Jonathan H; Brinkmeyer-Langford, Candice L; Gupte, Manisha; Smith, Holly M; Sengsayadeth, Seng; Sawyer, Douglas B; Benson, D Woodrow; Kornegay, Joe N; Markham, Larry W

    2016-04-01

    In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.

  6. Patient safety, quality of care, and knowledge translation in the intensive care unit.

    Science.gov (United States)

    Needham, Dale M

    2010-07-01

    A large gap exists between the completion of clinical research demonstrating the benefit of new treatment interventions and improved patient outcomes resulting from implementation of these interventions as part of routine clinical practice. This gap clearly affects patient safety and quality of care. Knowledge translation is important for addressing this gap, but evaluation of the most appropriate and effective knowledge translation methods is still ongoing. Through describing one model for knowledge translation and an example of its implementation, insights can be gained into systematic methods for advancing the implementation of evidence-based interventions to improve safety, quality, and patient outcomes.

  7. The Development of Translational Biomarkers as a Tool for Improving the Understanding, Diagnosis and Treatment of Chronic Neuropathic Pain.

    Science.gov (United States)

    Buckley, David A; Jennings, Elaine M; Burke, Nikita N; Roche, Michelle; McInerney, Veronica; Wren, Jonathan D; Finn, David P; McHugh, Patrick C

    2018-03-01

    Chronic neuropathic pain (CNP) is one of the most significant unmet clinical needs in modern medicine. Alongside the lack of effective treatments, there is a great deficit in the availability of objective diagnostic methods to reliably facilitate an accurate diagnosis. We therefore aimed to determine the feasibility of a simple diagnostic test by analysing differentially expressed genes in the blood of patients diagnosed with CNP of the lower back and compared to healthy human controls. Refinement of microarray expression data was performed using correlation analysis with 3900 human 2-colour microarray experiments. Selected genes were analysed in the dorsal horn of Sprague-Dawley rats after L5 spinal nerve ligation (SNL), using qRT-PCR and ddPCR, to determine possible associations with pathophysiological mechanisms underpinning CNP and whether they represent translational biomarkers of CNP. We found that of the 15 potential biomarkers identified, tissue inhibitor of matrix metalloproteinase-1 (TIMP1) gene expression was upregulated in chronic neuropathic lower back pain (CNBP) (p = 0.0049) which positively correlated (R = 0.68, p = ≤0.05) with increased plasma TIMP1 levels in this group (p = 0.0433). Moreover, plasma TIMP1 was also significantly upregulated in CNBP than chronic inflammatory lower back pain (p = 0.0272). In the SNL model, upregulation of the Timp1 gene was also observed (p = 0.0058) alongside a strong trend for the upregulation of melanocortin 1 receptor (p = 0.0847). Our data therefore highlights several genes that warrant further investigation, and of these, TIMP1 shows the greatest potential as an accessible and translational CNP biomarker.

  8. Lipidomics in translational research and the clinical significance of lipid-based biomarkers.

    Science.gov (United States)

    Stephenson, Daniel J; Hoeferlin, L Alexis; Chalfant, Charles E

    2017-11-01

    Lipidomics is a rapidly developing field of study that focuses on the identification and quantitation of various lipid species in the lipidome. Lipidomics has now emerged in the forefront of scientific research due to the importance of lipids in metabolism, cancer, and disease. Using both targeted and untargeted mass spectrometry as a tool for analysis, progress in the field has rapidly progressed in the last decade. Having the ability to assess these small molecules in vivo has led to better understanding of several lipid-driven mechanisms and the identification of lipid-based biomarkers in neurodegenerative disease, cancer, sepsis, wound healing, and pre-eclampsia. Biomarker identification and mechanistic understanding of specific lipid pathways linked to a disease's pathologies can form the foundation in the development of novel therapeutics in hopes of curing human disease. Published by Elsevier Inc.

  9. Cultural safety and the challenges of translating critically oriented knowledge in practice.

    Science.gov (United States)

    Browne, Annette J; Varcoe, Colleen; Smye, Victoria; Reimer-Kirkham, Sheryl; Lynam, M Judith; Wong, Sabrina

    2009-07-01

    Cultural safety is a relatively new concept that has emerged in the New Zealand nursing context and is being taken up in various ways in Canadian health care discourses. Our research team has been exploring the relevance of cultural safety in the Canadian context, most recently in relation to a knowledge-translation study conducted with nurses practising in a large tertiary hospital. We were drawn to using cultural safety because we conceptualized it as being compatible with critical theoretical perspectives that foster a focus on power imbalances and inequitable social relationships in health care; the interrelated problems of culturalism and racialization; and a commitment to social justice as central to the social mandate of nursing. Engaging in this knowledge-translation study has provided new perspectives on the complexities, ambiguities and tensions that need to be considered when using the concept of cultural safety to draw attention to racialization, culturalism, and health and health care inequities. The philosophic analysis discussed in this paper represents an epistemological grounding for the concept of cultural safety that links directly to particular moral ends with social justice implications. Although cultural safety is a concept that we have firmly positioned within the paradigm of critical inquiry, ambiguities associated with the notions of 'culture', 'safety', and 'cultural safety' need to be anticipated and addressed if they are to be effectively used to draw attention to critical social justice issues in practice settings. Using cultural safety in practice settings to draw attention to and prompt critical reflection on politicized knowledge, therefore, brings an added layer of complexity. To address these complexities, we propose that what may be required to effectively use cultural safety in the knowledge-translation process is a 'social justice curriculum for practice' that would foster a philosophical stance of critical inquiry at both the

  10. (Mis)Perceptions of Continuing Education: Insights from Knowledge Translation, Quality Improvement, and Patient Safety Leaders

    Science.gov (United States)

    Kitto, Simon C.; Bell, Mary; Goldman, Joanne; Peller, Jennifer; Silver, Ivan; Sargeant, Joan; Reeves, Scott

    2013-01-01

    Introduction: Minimal attention has been given to the intersection and potential collaboration among the domains of continuing education (CE), knowledge translation (KT), quality improvement (QI), and patient safety (PS), despite their overlapping objectives. A study was undertaken to examine leaders' perspectives of these 4 domains and their…

  11. New concepts and challenges in the clinical translation of cancer preventive therapies: the role of pharmacodynamic biomarkers.

    Science.gov (United States)

    Brown, Karen; Rufini, Alessandro

    2015-01-01

    Implementation of therapeutic cancer prevention strategies has enormous potential for reducing cancer incidence and related mortality. Trials of drugs including tamoxifen and aspirin have led the way in demonstrating proof-of-principle that prevention of breast and colorectal cancer is feasible. Many other compounds ranging from drugs in widespread use for various indications, including metformin, bisphosphonates, and vitamin D, to dietary agents such as the phytochemicals resveratrol and curcumin, show preventive activity against several cancers in preclinical models. Notwithstanding the wealth of opportunities, major challenges have hindered the development process and only a handful of therapies are currently approved for cancer risk reduction. One of the major obstacles to successful clinical translation of promising preventive agents is a lack of pharmacodynamic biomarkers to provide an early read out of biological activity in humans and for optimising doses to take into large scale randomised clinical trials. A further confounding factor is a lack of consideration of clinical pharmacokinetics in the design of preclinical experiments, meaning results are frequently reported from studies that use irrelevant or unachievable concentrations. This article focuses on recent findings from investigations with dietary-derived agents to illustrate how a thorough understanding of the mechanisms of action, using models that mimic the clinical scenario, together with the development of compound-specific accompanying pharmacodynamic biomarkers could accelerate the developmental pipeline for preventive agents and maximise the chances of success in future clinical trials. Moreover, the concept of a bell-shaped dose-response curve for therapeutic cancer prevention is discussed, along with the need to rethink the traditional 'more is better' approach for dose selection.

  12. Gamma synchrony: towards a translational biomarker for the treatment resistant symptoms of schizophrenia

    Science.gov (United States)

    Gandal, Michael J.; Edgar, J. Christopher; Klook, Kerstin; Siegel, Steven J.

    2011-01-01

    The lack of efficacy for antipsychotics with respect to negative symptoms and cognitive deficits is a significant obstacle for the treatment of schizophrenia. Developing new drugs to target these symptoms requires appropriate neural biomarkers that can be investigated in model organisms, be used to track treatment response, and provide insight into pathophysiological disease mechanisms. A growing body of evidence indicates that neural oscillations in the gamma frequency range (30–80 Hz) are disturbed in schizophrenia. Gamma synchrony has been shown to mediate a host of sensory and cognitive functions, including perceptual encoding, selective attention, salience, and working memory – neurocognitive processes that are dysfunctional in schizophrenia and largely refractory to treatment. This review summarizes the current state of clinical literature with respect to gamma band responses (GBRs) in schizophrenia, focusing on resting and auditory paradigms. Next, preclinical studies of schizophrenia that have investigated gamma band activity are reviewed to gain insight into neural mechanisms associated with these deficits. We conclude that abnormalities in gamma synchrony are ubiquitous in schizophrenia and likely reflect an elevation in baseline cortical gamma synchrony (‘noise’) coupled with reduced stimulus-evoked GBRs (‘signal’). Such a model likely reflects hippocampal and cortical dysfunction, as well as reduced glutamatergic signaling with downstream GABAergic deficits, but is probably less influenced by dopaminergic abnormalities implicated in schizophrenia. Finally, we propose that analogous signal-to-noise deficits in the flow of cortical information in preclinical models are useful targets for the development of new drugs that target the treatment-resistant symptoms of schizophrenia. PMID:21349276

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  14. Positioning Continuing Education: Boundaries and Intersections between the Domains Continuing Education, Knowledge Translation, Patient Safety and Quality Improvement

    Science.gov (United States)

    Kitto, Simon; Bell, Mary; Peller, Jennifer; Sargeant, Joan; Etchells, Edward; Reeves, Scott; Silver, Ivan

    2013-01-01

    Public and professional concern about health care quality, safety and efficiency is growing. Continuing education, knowledge translation, patient safety and quality improvement have made concerted efforts to address these issues. However, a coordinated and integrated effort across these domains is lacking. This article explores and discusses the…

  15. Safety, tolerability, and biomarkers of the treatment of mice with aerosolized toll-like receptor ligands

    Directory of Open Access Journals (Sweden)

    Victoria eAlfaro

    2014-02-01

    Full Text Available We have previously discovered a synergistically therapeutic combination of two Toll-like receptor (TLR ligands, an oligodeoxynucleotide (ODN and Pam2CSK4. Aerosolization of these ligands stimulates innate immunity within the lungs to prevent pneumonia from bacterial and viral pathogens. Here we examined the safety and tolerability of this treatment in mice, and characterized the expression of biomarkers of innate immune activation. We found that neutrophils appeared in lung lavage fluid 4 hours after treatment, reached a peak at 48 hours, and resolved by 7 days. The peak of neutrophil influx was accompanied by a small increase in lung permeability. Despite the abundance of neutrophils in lung lavage fluid, only rare neutrophils were visible histopathologically in the interstitium surrounding bronchi and veins and none were visible in alveolar airspaces. The cytokines IL-6, TNF and CXCL2 rose several hundred-fold in lung lavage fluid 4 hours after treatment in a dose-dependent and synergistic manner, providing useful biomarkers of lung activation. IL-6 rose five-fold in serum with delayed kinetics compared to its rise in lavage fluid, and might serve as a systemic biomarker of immune activation of the lungs. The dose-response relationship of lavage fluid cytokines was preserved in mice that underwent myeloablative treatment with cytosine arabinoside to model the treatment of hematologic malignancy. There were no overt signs of distress in mice treated with ODN/Pam2CSK4 in doses up to 8-fold the therapeutic dose, and no changes in temperature, respiratory rate, or behavioral signs of sickness including sugar water preference, food disappearance, cage exploration or social interaction, though there was a small degree of transient weight loss. We conclude that treatment with aerosolized ODN/Pam2CSK4 is well tolerated in mice, and that innate immune activation of the lungs can be monitored by the measurement of inflammatory cytokines in lung lavage

  16. The current status of biomarkers for predicting toxicity

    Science.gov (United States)

    Campion, Sarah; Aubrecht, Jiri; Boekelheide, Kim; Brewster, David W; Vaidya, Vishal S; Anderson, Linnea; Burt, Deborah; Dere, Edward; Hwang, Kathleen; Pacheco, Sara; Saikumar, Janani; Schomaker, Shelli; Sigman, Mark; Goodsaid, Federico

    2013-01-01

    Introduction There are significant rates of attrition in drug development. A number of compounds fail to progress past preclinical development due to limited tools that accurately monitor toxicity in preclinical studies and in the clinic. Research has focused on improving tools for the detection of organ-specific toxicity through the identification and characterization of biomarkers of toxicity. Areas covered This article reviews what we know about emerging biomarkers in toxicology, with a focus on the 2012 Northeast Society of Toxicology meeting titled ‘Translational Biomarkers in Toxicology.’ The areas covered in this meeting are summarized and include biomarkers of testicular injury and dysfunction, emerging biomarkers of kidney injury and translation of emerging biomarkers from preclinical species to human populations. The authors also provide a discussion about the biomarker qualification process and possible improvements to this process. Expert opinion There is currently a gap between the scientific work in the development and qualification of novel biomarkers for nonclinical drug safety assessment and how these biomarkers are actually used in drug safety assessment. A clear and efficient path to regulatory acceptance is needed so that breakthroughs in the biomarker toolkit for nonclinical drug safety assessment can be utilized to aid in the drug development process. PMID:23961847

  17. Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

    International Nuclear Information System (INIS)

    Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

    2010-01-01

    In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg -1 day -1 or 250 mg kg -1 day -1 for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

  18. Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Bhowmik Salil [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of); Lee, Young-Joo; Yi, Hong Jae [College of Pharmacy, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul 130-791 (Korea, Republic of); Chung, Bong Chul [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); Jung, Byung Hwa, E-mail: jbhluck@kist.re.kr [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of)

    2010-02-19

    In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg{sup -1} day{sup -1} or 250 mg kg{sup -1} day{sup -1} for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

  19. Trustworthy Variant Derivation with Translation Validation for Safety Critical Product Lines

    DEFF Research Database (Denmark)

    Iosif-Lazăr, Alexandru Florin; Wasowski, Andrzej

    2016-01-01

    Software product line (SPL) engineering facilitates development of entire families of software products with systematic reuse. Model driven SPLs use models in the design and development process. In the safety critical domain, validation of models and testing of code increases the quality...... of the products altogether. However, to maintain this trustworthiness it is necessary to know that the SPL tools, which manipulate models and code to derive concrete product variants, do not introduce errors in the process. We propose a general technique of checking correctness of product derivation tools through...... translation validation. We demonstrate it using Featherweight VML—a core language for separate variability modeling relying on a single kind of variation point to define transformations of artifacts seen as object models. We use Featherweight VML with its semantics as a correctness specification...

  20. Automated Translation of Safety Critical Application Software Specifications into PLC Ladder Logic

    Science.gov (United States)

    Leucht, Kurt W.; Semmel, Glenn S.

    2008-01-01

    The numerous benefits of automatic application code generation are widely accepted within the software engineering community. A few of these benefits include raising the abstraction level of application programming, shorter product development time, lower maintenance costs, and increased code quality and consistency. Surprisingly, code generation concepts have not yet found wide acceptance and use in the field of programmable logic controller (PLC) software development. Software engineers at the NASA Kennedy Space Center (KSC) recognized the need for PLC code generation while developing their new ground checkout and launch processing system. They developed a process and a prototype software tool that automatically translates a high-level representation or specification of safety critical application software into ladder logic that executes on a PLC. This process and tool are expected to increase the reliability of the PLC code over that which is written manually, and may even lower life-cycle costs and shorten the development schedule of the new control system at KSC. This paper examines the problem domain and discusses the process and software tool that were prototyped by the KSC software engineers.

  1. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma.

    Science.gov (United States)

    Weber, Jeffrey S; Kudchadkar, Ragini Reiney; Yu, Bin; Gallenstein, Donna; Horak, Christine E; Inzunza, H David; Zhao, Xiuhua; Martinez, Alberto J; Wang, Wenshi; Gibney, Geoffrey; Kroeger, Jodi; Eysmans, Cabell; Sarnaik, Amod A; Chen, Y Ann

    2013-12-01

    Nivolumab, a human immunoglobulin G4-blocking antibody against the T-cell programmed death-1 checkpoint protein, has activity against metastatic melanoma. Its safety, clinical efficacy, and correlative biomarkers were assessed with or without a peptide vaccine in ipilimumab-refractory and -naive melanoma. In this phase I study, 90 patients with unresectable stage III or IV melanoma who were ipilimumab naive and had experienced progression after at least one prior therapy (cohorts 1 to 3, 34 patients) or experienced progression after prior ipilimumab (cohorts 4 to 6, 56 patients) received nivolumab at 1, 3, or 10 mg/kg every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. Nivolumab with vaccine was well tolerated and safe at all doses. The RECIST 1.1 response rate for both ipilimumab-refractory and -naive patients was 25%. Median duration of response was not reached at a median of 8.1 months of follow-up. High pretreatment NY-ESO-1 and MART-1-specific CD8(+) T cells were associated with progression of disease. At week 12, increased peripheral-blood T regulatory cells and decreased antigen-specific T cells were associated with progression. PD-L1 tumor staining was associated with responses to nivolumab, but negative staining did not rule out a response. Patients who experienced progression after nivolumab could respond to ipilimumab. In patients with ipilimumab-refractory or -naive melanoma, nivolumab at 3 mg/kg with or without peptide vaccine was well tolerated and induced responses lasting up to 140 weeks. Responses to nivolumab in ipilimumab-refractory patients or to ipilimumab in nivolumab-refractory patients support combination or sequencing of nivolumab and ipilimumab.

  2. Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma.

    Science.gov (United States)

    Boige, Valérie; Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. The 16W-DCR was 42% (95% confidence interval, 27%-57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3-4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation.

  3. Trends in qualifying biomarkers in drug safety. Consensus of the 2011 meeting of the spanish society of clinical pharmacology.

    Science.gov (United States)

    Agúndez, José A G; Del Barrio, Jaime; Padró, Teresa; Stephens, Camilla; Farré, Magí; Andrade, Raúl J; Badimon, Lina; García-Martín, Elena; Vilahur, Gemma; Lucena, M Isabel

    2012-01-01

    In this paper we discuss the consensus view on the use of qualifying biomarkers in drug safety, raised within the frame of the XXIV meeting of the Spanish Society of Clinical Pharmacology held in Málaga (Spain) in October, 2011. The widespread use of biomarkers as surrogate endpoints is a goal that scientists have long been pursuing. Thirty years ago, when molecular pharmacogenomics evolved, we anticipated that these genetic biomarkers would soon obviate the routine use of drug therapies in a way that patients should adapt to the therapy rather than the opposite. This expected revolution in routine clinical practice never took place as quickly nor with the intensity as initially expected. The concerted action of operating multicenter networks holds great promise for future studies to identify biomarkers related to drug toxicity and to provide better insight into the underlying pathogenesis. Today some pharmacogenomic advances are already widely accepted, but pharmacogenomics still needs further development to elaborate more precise algorithms and many barriers to implementing individualized medicine exist. We briefly discuss our view about these barriers and we provide suggestions and areas of focus to advance in the field.

  4. Biomarker-driven phenotyping in Parkinson disease: a translational missing link in disease-modifying clinical trials

    Science.gov (United States)

    Espay, Alberto J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Fernandez, Hubert H; Simon, David K.; Leverenz, James B.; Merola, Aristide; Chen-Plotkin, Alice; Brundin, Patrik; Kauffman, Marcelo A.; Erro, Roberto; Kieburtz, Karl; Woo, Daniel; Macklin, Eric A.; Standaert, David G.; Lang, Anthony E.

    2016-01-01

    Past clinical trials of putative neuroprotective therapies have targeted Parkinson disease (PD) as a single pathogenic disease entity. From an Oslerian clinico-pathologic perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: a single-mechanism therapy can affect most of those sharing the classic pathologic hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers) rather than clinical definitions are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller but well-defined subsets of PD amenable to successful neuroprotection. PMID:28233927

  5. Model-based analysis of thromboxane B2 and prostaglandin E2 as biomarkers in the safety evaluation of naproxen

    International Nuclear Information System (INIS)

    Sahota, Tarjinder; Sanderson, Ian; Danhof, Meindert; Della Pasqua, Oscar

    2014-01-01

    The assessment of safety in traditional toxicology protocols relies on evidence arising from observed adverse events (AEs) in animals and on establishing their correlation with different measures of drug exposure (e.g., C max and AUC). Such correlations, however, ignore the role of biomarkers, which can provide further insight into the underlying pharmacological mechanisms. Here we use naproxen as a paradigm drug to explore the feasibility of a biomarker-guided approach for the prediction of AEs in humans. A standard toxicology protocol was set up for the evaluation of effects of naproxen in rat, in which four doses were tested (7.5, 15, 40 and 80 mg/kg). In addition to sparse blood sampling for the assessment of exposure, thromboxane B 2 and prostaglandin E 2 were also collected in satellite groups. Nonlinear mixed effects modelling was used to evaluate the predictive performance of the approach. A one-compartmental model with first order absorption was found to best describe the pharmacokinetics of naproxen. A nonlinear relationship between dose and bioavailability was observed which leads to a less than proportional increase in naproxen concentrations with increasing doses. The pharmacodynamics of TXB 2 and PGE 2 was described by direct inhibition models with maximum pharmacological effects achieved at doses > 7.5 mg/kg. The predicted PKPD relationship in humans was within 10-fold of the values previously published. Moreover, our results indicate that biomarkers can be used to assess interspecies differences in PKPD and extrapolated data from animals to humans. Biomarker sampling should be used systematically in general toxicity studies. - Highlights: • Prediction of a drug's safety profile from preclinical protocols remains challenging. • Pharmacokinetic measures of safe exposure (e.g., AUC) ignore the role of biomarkers. • PKPD relationships enable the evaluation of adverse events in a mechanistic manner. • Major differences exist between rats and

  6. International review on safety requirements for the prototype fast breeder reactor “Monju” (Translated document)

    International Nuclear Information System (INIS)

    2016-02-01

    In response to the lessons learned from the serious nuclear accidents at the TEPCO's Fukushima Daiichi Nuclear Power Stations, an advisory committee, which was set up by the Japan Atomic Energy Agency, issued the report “Safety Requirements Expected to the Prototype Fast Breeder Reactor Monju” taking into account the SFR specific safety characteristics in July 2014. The report was reviewed by the leading international experts on SFR safety from five countries and one international organization in order to obtain independent and objective evaluation. The international review comments on each subsection were collected and compiled, and then a summary of results was derived through the discussion at the review meeting and individual feedbacks. As a result the basic concept for prevention of severe accidents and mitigation of their consequences of Monju is appropriate in consideration of SFR specific safety characteristics, and is in accordance with international common understanding. (author)

  7. Translational PKPD modeling in schizophrenia: linking receptor occupancy of antipsychotics to efficacy and safety

    NARCIS (Netherlands)

    Pilla Reddy, Venkatesh; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

    2012-01-01

    Objectives: To link the brain dopamine D2 receptor occupancy (D2RO) of antipsychotic drugs with clinical endpoints of efficacy and safety to assess the therapeutic window of D2RO. Methods: Pharmacokinetic-Pharmacodynamic (PK-PD) models were developed to predict the D2 receptor occupancy of

  8. Translating self-persuasion into an adolescent HPV vaccine promotion intervention for parents attending safety-net clinics.

    Science.gov (United States)

    Baldwin, Austin S; Denman, Deanna C; Sala, Margarita; Marks, Emily G; Shay, L Aubree; Fuller, Sobha; Persaud, Donna; Lee, Simon Craddock; Skinner, Celette Sugg; Wiebe, Deborah J; Tiro, Jasmin A

    2017-04-01

    Self-persuasion is an effective behavior change strategy, but has not been translated for low-income, less educated, uninsured populations attending safety-net clinics or to promote human papillomavirus (HPV) vaccination. We developed a tablet-based application (in English and Spanish) to elicit parental self-persuasion for adolescent HPV vaccination and evaluated its feasibility in a safety-net population. Parents (N=45) of age-eligible adolescents used the self-persuasion application. Then, during cognitive interviews, staff gathered quantitative and qualitative feedback on the self-persuasion tasks including parental decision stage. The self-persuasion tasks were rated as easy to complete and helpful. We identified six question prompts rated as uniformly helpful, not difficult to answer, and generated non-redundant responses from participants. Among the 33 parents with unvaccinated adolescents, 27 (81.8%) reported deciding to get their adolescent vaccinated after completing the self-persuasion tasks. The self-persuasion application was feasible and resulted in a change in parents' decision stage. Future studies can now test the efficacy of the tablet-based application on HPV vaccination. The self-persuasion application facilitates verbalization of reasons for HPV vaccination in low literacy, safety-net settings. This self-administered application has the potential to be more easily incorporated into clinical practice than other patient education approaches. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Employing the arts for knowledge production and translation: Visualizing new possibilities for women speaking up about safety concerns in maternity.

    Science.gov (United States)

    Mackintosh, Nicola; Sandall, Jane; Collison, Claire; Carter, Wendy; Harris, James

    2018-06-01

    This project used animated film to translate research findings into accessible health information aimed at enabling women to speak up and secure professional help for serious safety concerns during pregnancy and after birth. We tested as proof of concept our use of the arts both as product (knowledge production) and process (enabling involvement). Emergencies during pregnancy and birth, while unusual, can develop rapidly and unexpectedly, with catastrophic consequences. Women's tacit knowledge of changes in their condition is an important resource to aid early detection, but women can worry about the legitimacy of their concerns and struggle to get these taken seriously by staff. Arts-based knowledge translation. A user group of women who had experienced complications in the perinatal period (n = 34) helped us develop and pilot test the animation. Obstetricians and midwives (15), clinical leads (3) and user group representatives (8) helped with the design and testing. The consultation process, script and storyboard enabled active interaction with the evidence, meaningful engagement with stakeholders and new understandings about securing help for perinatal complications. The method enabled us to address gender stereotypes and social norms about speaking up and embed a social script for women within the animation, to help structure their help seeking. While for some women, there was an emotional burden, the majority were glad to have been part of the animation's development and felt it had enabled their voices to be heard. This project has demonstrated the benefits of arts-science collaborations for meaningful co-production and effective translation of research evidence. © 2017 The Authors. Health Expectations published by John Wiley & Sons Ltd.

  10. Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD.

    Science.gov (United States)

    Wallace, Lindsay M; Saad, Nizar Y; Pyne, Nettie K; Fowler, Allison M; Eidahl, Jocelyn O; Domire, Jacqueline S; Griffin, Danielle A; Herman, Adam C; Sahenk, Zarife; Rodino-Klapac, Louise R; Harper, Scott Q

    2018-03-16

    RNAi emerged as a prospective molecular therapy nearly 15 years ago. Since then, two major RNAi platforms have been under development: oligonucleotides and gene therapy. Oligonucleotide-based approaches have seen more advancement, with some promising therapies that may soon reach market. In contrast, vector-based approaches for RNAi therapy have remained largely in the pre-clinical realm, with limited clinical safety and efficacy data to date. We are developing a gene therapy approach to treat the autosomal-dominant disorder facioscapulohumeral muscular dystrophy. Our strategy involves silencing the myotoxic gene DUX4 using adeno-associated viral vectors to deliver targeted microRNA expression cassettes (miDUX4s). We previously demonstrated proof of concept for this approach in mice, and we are now taking additional steps here to assess safety issues related to miDUX4 overexpression and sequence-specific off-target silencing. In this study, we describe improvements in vector design and expansion of our miDUX4 sequence repertoire and report differential toxicity elicited by two miDUX4 sequences, of which one was toxic and the other was not. This study provides important data to help advance our goal of translating RNAi gene therapy for facioscapulohumeral muscular dystrophy.

  11. Biomarkers of safety and immune protection for genetically modified live attenuated leishmania vaccines against visceral leishmaniasis - discovery and implications.

    Science.gov (United States)

    Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L

    2014-01-01

    Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen(-/-) in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal

  12. Biomarkers of Safety and Immune Protection for Genetically Modified Live Attenuated Leishmania Vaccines Against Visceral Leishmaniasis – Discovery and Implications

    Science.gov (United States)

    Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L.

    2014-01-01

    Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen−/− in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal

  13. Utility of specific biomarkers to assess safety of swine manure for biofertilizing purposes.

    Science.gov (United States)

    Fongaro, G; Viancelli, A; Magri, M E; Elmahdy, E M; Biesus, L L; Kich, J D; Kunz, A; Barardi, C R M

    2014-05-01

    Swine production is an important economic activity in Brazil, and there is interest in the development of clean production mechanisms to support sustainable agro-industrial activities. The biomass derived from swine manure has good potential to be used as a biofertilizer due to its high nutrient concentration. However, the land application of manure should be based on safety parameters such as the presence of pathogens that can potentially infect animals and people. This study was designed to assess the presence of porcine circovirus-2 (PCV2), porcine adenovirus (PAdV), rotavirus-A (RV-A) and Salmonella spp. in liquid manure, as well the infectivity of two genotypes of circovirus-2 (PCV2a and PCV2b) present in liquid manure. Three swine farms were evaluated: 1) a nursery production farm (manure analyzed before and after anaerobic biodigestion), 2) a grow-finish production farm (analyzed before and after anaerobic biodigestion), and 3) a second grow-finish production farm (raw manure-affluent). PCV2, PAdV and RV-A were present before and after anaerobic biodigestion (either affluent or effluent) at all farms. Salmonella spp. were detected at farm 1 (affluent and effluent) and farm 3 (raw manure-affluent) but not farm 2 (affluent and effluent). When the ability of the anaerobic biodigestion process to reduce viral concentration was evaluated, no significant reduction was observed (P>0.05). Both the PCV2a and PCV2b genotypes were detected, suggesting viral co-infection in swine production. The results revealed infectious PCV2 even after anaerobic biodigestion treatment. The presence of Salmonella spp. and enteric viruses, especially infectious PCV2, in the final effluent from the anaerobic biodigester system suggests that the process is inefficient for pathogen inactivation. Due to the prevalence and infectivity of PCV2 and considering the successful use of molecular methods coupled to cell culture for detecting infectious PCV2, we suggest that this virus can be used

  14. Biomarkers of safety and immune protection for genetically modified live attenuated Leishmania vaccines against visceral leishmaniasis-Discovery and implications

    Directory of Open Access Journals (Sweden)

    Sreenivas eGannavaram

    2014-05-01

    Full Text Available Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated

  15. Systematic Review of Human and Animal Studies Examining the Efficacy and Safety of N-Acetylcysteine (NAC) and N-Acetylcysteine Amide (NACA) in Traumatic Brain Injury: Impact on Neurofunctional Outcome and Biomarkers of Oxidative Stress and Inflammation.

    Science.gov (United States)

    Bhatti, Junaid; Nascimento, Barto; Akhtar, Umbreen; Rhind, Shawn G; Tien, Homer; Nathens, Avery; da Luz, Luis Teodoro

    2017-01-01

    No new therapies for traumatic brain injury (TBI) have been officially translated into current practice. At the tissue and cellular level, both inflammatory and oxidative processes may be exacerbated post-injury and contribute to further brain damage. N- acetylcysteine (NAC) has the potential to downregulate both processes. This review focuses on the potential neuroprotective utility of NAC and N -acetylcysteine amide (NACA) post-TBI. Medline, Embase, Cochrane Library, and ClinicalTrials.gov were searched up to July 2017. Studies that examined clinical and laboratory effects of NAC and NACA post-TBI in human and animal studies were included. Risk of bias was assessed in human and animal studies according to the design of each study (randomized or not). The primary outcome assessed was the effect of NAC/NACA treatment on functional outcome, while secondary outcomes included the impact on biomarkers of inflammation and oxidation. Due to the clinical and methodological heterogeneity observed across studies, no meta-analyses were conducted. Our analyses revealed only three human trials, including two randomized controlled trials (RCTs) and 20 animal studies conducted using standardized animal models of brain injury. The two RCTs reported improvement in the functional outcome post-NAC/NACA administration. Overall, the evidence from animal studies is more robust and demonstrated substantial improvement of cognition and psychomotor performance following NAC/NACA use. Animal studies also reported significantly more cortical sparing, reduced apoptosis, and lower levels of biomarkers of inflammation and oxidative stress. No safety concerns were reported in any of the studies included in this analysis. Evidence from the animal literature demonstrates a robust association for the prophylactic application of NAC and NACA post-TBI with improved neurofunctional outcomes and downregulation of inflammatory and oxidative stress markers at the tissue level. While a growing body of

  16. Systematic Review of Human and Animal Studies Examining the Efficacy and Safety of N-Acetylcysteine (NAC and N-Acetylcysteine Amide (NACA in Traumatic Brain Injury: Impact on Neurofunctional Outcome and Biomarkers of Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Junaid Bhatti

    2018-01-01

    Full Text Available BackgroundNo new therapies for traumatic brain injury (TBI have been officially translated into current practice. At the tissue and cellular level, both inflammatory and oxidative processes may be exacerbated post-injury and contribute to further brain damage. N-acetylcysteine (NAC has the potential to downregulate both processes. This review focuses on the potential neuroprotective utility of NAC and N-acetylcysteine amide (NACA post-TBI.MethodsMedline, Embase, Cochrane Library, and ClinicalTrials.gov were searched up to July 2017. Studies that examined clinical and laboratory effects of NAC and NACA post-TBI in human and animal studies were included. Risk of bias was assessed in human and animal studies according to the design of each study (randomized or not. The primary outcome assessed was the effect of NAC/NACA treatment on functional outcome, while secondary outcomes included the impact on biomarkers of inflammation and oxidation. Due to the clinical and methodological heterogeneity observed across studies, no meta-analyses were conducted.ResultsOur analyses revealed only three human trials, including two randomized controlled trials (RCTs and 20 animal studies conducted using standardized animal models of brain injury. The two RCTs reported improvement in the functional outcome post-NAC/NACA administration. Overall, the evidence from animal studies is more robust and demonstrated substantial improvement of cognition and psychomotor performance following NAC/NACA use. Animal studies also reported significantly more cortical sparing, reduced apoptosis, and lower levels of biomarkers of inflammation and oxidative stress. No safety concerns were reported in any of the studies included in this analysis.ConclusionEvidence from the animal literature demonstrates a robust association for the prophylactic application of NAC and NACA post-TBI with improved neurofunctional outcomes and downregulation of inflammatory and oxidative stress markers at

  17. Model-based analysis of thromboxane B{sub 2} and prostaglandin E{sub 2} as biomarkers in the safety evaluation of naproxen

    Energy Technology Data Exchange (ETDEWEB)

    Sahota, Tarjinder; Sanderson, Ian; Danhof, Meindert [Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden (Netherlands); Della Pasqua, Oscar [Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden (Netherlands); Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline, Uxbridge (United Kingdom)

    2014-08-01

    The assessment of safety in traditional toxicology protocols relies on evidence arising from observed adverse events (AEs) in animals and on establishing their correlation with different measures of drug exposure (e.g., C{sub max} and AUC). Such correlations, however, ignore the role of biomarkers, which can provide further insight into the underlying pharmacological mechanisms. Here we use naproxen as a paradigm drug to explore the feasibility of a biomarker-guided approach for the prediction of AEs in humans. A standard toxicology protocol was set up for the evaluation of effects of naproxen in rat, in which four doses were tested (7.5, 15, 40 and 80 mg/kg). In addition to sparse blood sampling for the assessment of exposure, thromboxane B{sub 2} and prostaglandin E{sub 2} were also collected in satellite groups. Nonlinear mixed effects modelling was used to evaluate the predictive performance of the approach. A one-compartmental model with first order absorption was found to best describe the pharmacokinetics of naproxen. A nonlinear relationship between dose and bioavailability was observed which leads to a less than proportional increase in naproxen concentrations with increasing doses. The pharmacodynamics of TXB{sub 2} and PGE{sub 2} was described by direct inhibition models with maximum pharmacological effects achieved at doses > 7.5 mg/kg. The predicted PKPD relationship in humans was within 10-fold of the values previously published. Moreover, our results indicate that biomarkers can be used to assess interspecies differences in PKPD and extrapolated data from animals to humans. Biomarker sampling should be used systematically in general toxicity studies. - Highlights: • Prediction of a drug's safety profile from preclinical protocols remains challenging. • Pharmacokinetic measures of safe exposure (e.g., AUC) ignore the role of biomarkers. • PKPD relationships enable the evaluation of adverse events in a mechanistic manner. • Major

  18. Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

    International Nuclear Information System (INIS)

    Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y.

    2014-01-01

    The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

  19. Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y., E-mail: frank.hsieh@nextcea.com

    2014-09-15

    The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

  20. Reverse translation of phase I biomarker findings links the activity of angiotensin-(1–7) to repression of hypoxia inducible factor-1α in vascular sarcomas

    International Nuclear Information System (INIS)

    Petty, W Jeffrey; Aklilu, Mebea; Varela, Victor A; Lovato, James; Savage, Paul D; Miller, Antonius A

    2012-01-01

    In a phase I study of angiotensin-(1–7) [Ang-(1–7)], clinical benefit was associated with reduction in plasma placental growth factor (PlGF) concentrations. The current study examines Ang-(1–7) induced changes in biomarkers according to cancer type and investigates mechanisms of action engaged in vitro. Plasma biomarkers were measured prior to Ang-(1–7) administration as well as 1, 2, 3, 4, and 6 hours after treatment. Tests for interaction were performed to determine the impact of cancer type on angiogenic hormone levels. If a positive interaction was detected, treatment-induced biomarker changes for individual cancer types were assessed. To investigate mechanisms of action, in vitro growth assays were performed using a murine endothelioma cell line (EOMA). PCR arrays were performed to identify and statistically validate genes that were altered by Ang-(1–7) treatment in these cells. Tests for interaction controlled for dose cohort and clinical response indicated a significant impact of cancer type on post-treatment VEGF and PlGF levels. Following treatment, PlGF levels decreased over time in patients with sarcoma (P = .007). Treatment of EOMA cells with increasing doses of Ang-(1–7) led to significant growth suppression at doses as low as 100 nM. PCR arrays identified 18 genes that appeared to have altered expression after Ang-(1–7) treatment. Replicate analyses confirmed significant changes in 8 genes including reduction in PlGF (P = .04) and hypoxia inducible factor 1α (HIF-1α) expression (P < .001). Ang-(1–7) has clinical and pre-clinical activity for vascular sarcomas that is linked to reduced HIF-1α and PlGF expression

  1. Translation Theory 'Translated'

    DEFF Research Database (Denmark)

    Wæraas, Arild; Nielsen, Jeppe

    2016-01-01

    Translation theory has proved to be a versatile analytical lens used by scholars working from different traditions. On the basis of a systematic literature review, this study adds to our understanding of the ‘translations’ of translation theory by identifying the distinguishing features of the most...... common theoretical approaches to translation within the organization and management discipline: actor-network theory, knowledge-based theory, and Scandinavian institutionalism. Although each of these approaches already has borne much fruit in research, the literature is diverse and somewhat fragmented......, but also overlapping. We discuss the ways in which the three versions of translation theory may be combined and enrich each other so as to inform future research, thereby offering a more complete understanding of translation in and across organizational settings....

  2. Clinical Translation and Validation of a Predictive Biomarker for Patritumab, an Anti-human Epidermal Growth Factor Receptor 3 (HER3) Monoclonal Antibody, in Patients With Advanced Non-small Cell Lung Cancer.

    Science.gov (United States)

    Mendell, Jeanne; Freeman, Daniel J; Feng, Wenqin; Hettmann, Thore; Schneider, Matthias; Blum, Sabine; Ruhe, Jens; Bange, Johannes; Nakamaru, Kenji; Chen, Shuquan; Tsuchihashi, Zenta; von Pawel, Joachim; Copigneaux, Catherine; Beckman, Robert A

    2015-03-01

    During early clinical development, prospective identification of a predictive biomarker and validation of an assay method may not always be feasible. Dichotomizing a continuous biomarker measure to classify responders also leads to challenges. We present a case study of a prospective-retrospective approach for a continuous biomarker identified after patient enrollment but defined prospectively before the unblinding of data. An analysis of the strengths and weaknesses of this approach and the challenges encountered in its practical application are also provided. HERALD (NCT02134015) was a double-blind, phase 2 study in patients with non-small cell lung cancer (NSCLC) randomized to erlotinib with placebo or with high or low doses of patritumab, a monoclonal antibody targeted against human epidermal growth factor receptor 3 (HER3). While the primary objective was to assess safety and progression-free survival (PFS), a secondary objective was to determine a single predictive biomarker hypothesis to identify subjects most likely to benefit from the addition of patritumab. Although not identified as the primary biomarker in the study protocol, on the basis of preclinical results from 2 independent laboratories, expression levels of the HER3 ligand heregulin (HRG) were prospectively declared the predictive biomarker before data unblinding but after subject enrollment. An assay to measure HRG mRNA was developed and validated. Other biomarkers, such as epidermal growth factor receptor (EGFR) mutation status, were also evaluated in an exploratory fashion. The cutoff value for high vs. low HRG mRNA levels was set at the median delta threshold cycle. A maximum likelihood analysis was performed to evaluate the provisional cutoff. The relationship of HRG values to PFS hazard ratios (HRs) was assessed as a measure of internal validation. Additional NSCLC samples were analyzed to characterize HRG mRNA distribution. The subgroup of patients with high HRG mRNA levels ("HRG

  3. Translational medicine: science or wishful thinking?

    Directory of Open Access Journals (Sweden)

    Wehling Martin

    2008-06-01

    Full Text Available Abstract "Translational medicine" as a fashionable term is being increasingly used to describe the wish of biomedical researchers to ultimately help patients. Despite increased efforts and investments into R&D, the output of novel medicines has been declining dramatically over the past years. Improvement of translation is thought to become a remedy as one of the reasons for this widening gap between input and output is the difficult transition between preclinical ("basic" and clinical stages in the R&D process. Animal experiments, test tube analyses and early human trials do simply not reflect the patient situation well enough to reliably predict efficacy and safety of a novel compound or device. This goal, however, can only be achieved if the translational processes are scientifically backed up by robust methods some of which still need to be developed. This mainly relates to biomarker development and predictivity assessment, biostatistical methods, smart and accelerated early human study designs and decision algorithms among other features. It is therefore claimed that a new science needs to be developed called 'translational science in medicine'.

  4. Understanding Translation

    DEFF Research Database (Denmark)

    Schjoldager, Anne Gram; Gottlieb, Henrik; Klitgård, Ida

    Understanding Translation is designed as a textbook for courses on the theory and practice of translation in general and of particular types of translation - such as interpreting, screen translation and literary translation. The aim of the book is to help you gain an in-depth understanding...... of the phenomenon of translation and to provide you with a conceptual framework for the analysis of various aspects of professional translation. Intended readers are students of translation and languages, but the book will also be relevant for others who are interested in the theory and practice of translation...... - translators, language teachers, translation users and literary, TV and film critics, for instance. Discussions focus on translation between Danish and English....

  5. Measurement of DNA biomarkers for the safety of tissue-engineered medical products, using artificial skin as a model.

    Science.gov (United States)

    Rodriguez, Henry; O'Connell, Catherine; Barker, Peter E; Atha, Donald H; Jaruga, Pawel; Birincioglu, Mustafa; Marino, Michael; McAndrew, Patricia; Dizdaroglu, Miral

    2004-01-01

    To test the hypothesis that the process of tissue engineering introduces genetic damage to tissue-engineered medical products, we employed the use of five state-of-the-art measurement technologies to measure a series of DNA biomarkers in commercially available tissue-engineered skin as a model. DNA was extracted from the skin and compared with DNA from cultured human neonatal control cells (dermal fibroblasts and epidermal keratinocytes) and adult human fibroblasts from a 55-year-old donor and a 96-year-old donor. To determine whether tissue engineering caused oxidative DNA damage, gas chromatography/isotope-dilution mass spectrometry and liquid chromatography/isotope-dilution mass spectrometry were used to measure six oxidatively modified DNA bases as biomarkers. Normal endogenous levels of the modified DNA biomarkers were not elevated in tissue-engineered skin when compared with control cells. Next, denaturing high-performance liquid chromatography and capillary electrophoresis-single strand conformation polymorphism were used to measure genetic mutations. Specifically, the TP53 tumor suppressor gene was screened for mutations, because it is the most commonly mutated gene in skin cancer. The tissue-engineered skin was found to be free of TP53 mutations at the level of sensitivity of these measurement technologies. Lastly, fluorescence in situ hybridization was employed to measure the loss of Y chromosome, which is associated with excessive cell passage and aging. Loss of Y chromosome was not detected in the tissue-engineered skin and cultured neonatal cells used as controls. In this study, we have demonstrated that tissue engineering (for TestSkin II) does not introduce genetic damage above the limits of detection of the state-of-the-art technologies used. This work explores the standard for measuring genetic damage that could be introduced during production of novel tissue-engineered products. More importantly, this exploratory work addresses technological

  6. Translation Techniques

    OpenAIRE

    Marcia Pinheiro

    2015-01-01

    In this paper, we discuss three translation techniques: literal, cultural, and artistic. Literal translation is a well-known technique, which means that it is quite easy to find sources on the topic. Cultural and artistic translation may be new terms. Whilst cultural translation focuses on matching contexts, artistic translation focuses on matching reactions. Because literal translation matches only words, it is not hard to find situations in which we should not use this technique.  Because a...

  7. Translational Medicine and Patient Safety in Europe: TRANSFoRm—Architecture for the Learning Health System in Europe

    Directory of Open Access Journals (Sweden)

    Brendan C. Delaney

    2015-01-01

    Full Text Available The Learning Health System (LHS describes linking routine healthcare systems directly with both research translation and knowledge translation as an extension of the evidence-based medicine paradigm, taking advantage of the ubiquitous use of electronic health record (EHR systems. TRANSFoRm is an EU FP7 project that seeks to develop an infrastructure for the LHS in European primary care. Methods. The project is based on three clinical use cases, a genotype-phenotype study in diabetes, a randomised controlled trial with gastroesophageal reflux disease, and a diagnostic decision support system for chest pain, abdominal pain, and shortness of breath. Results. Four models were developed (clinical research, clinical data, provenance, and diagnosis that form the basis of the projects approach to interoperability. These models are maintained as ontologies with binding of terms to define precise data elements. CDISC ODM and SDM standards are extended using an archetype approach to enable a two-level model of individual data elements, representing both research content and clinical content. Separate configurations of the TRANSFoRm tools serve each use case. Conclusions. The project has been successful in using ontologies and archetypes to develop a highly flexible solution to the problem of heterogeneity of data sources presented by the LHS.

  8. Translational Epidemiology in Psychiatry

    Science.gov (United States)

    Weissman, Myrna M.; Brown, Alan S.; Talati, Ardesheer

    2012-01-01

    Translational research generally refers to the application of knowledge generated by advances in basic sciences research translated into new approaches for diagnosis, prevention, and treatment of disease. This direction is called bench-to-bedside. Psychiatry has similarly emphasized the basic sciences as the starting point of translational research. This article introduces the term translational epidemiology for psychiatry research as a bidirectional concept in which the knowledge generated from the bedside or the population can also be translated to the benches of laboratory science. Epidemiologic studies are primarily observational but can generate representative samples, novel designs, and hypotheses that can be translated into more tractable experimental approaches in the clinical and basic sciences. This bedside-to-bench concept has not been explicated in psychiatry, although there are an increasing number of examples in the research literature. This article describes selected epidemiologic designs, providing examples and opportunities for translational research from community surveys and prospective, birth cohort, and family-based designs. Rapid developments in informatics, emphases on large sample collection for genetic and biomarker studies, and interest in personalized medicine—which requires information on relative and absolute risk factors—make this topic timely. The approach described has implications for providing fresh metaphors to communicate complex issues in interdisciplinary collaborations and for training in epidemiology and other sciences in psychiatry. PMID:21646577

  9. Investigative safety science as a competitive advantage for Pharma.

    Science.gov (United States)

    Moggs, Jonathan; Moulin, Pierre; Pognan, Francois; Brees, Dominique; Leonard, Michele; Busch, Steve; Cordier, Andre; Heard, David J; Kammüller, Michael; Merz, Michael; Bouchard, Page; Chibout, Salah-Dine

    2012-09-01

    Following a US National Academy of Sciences report in 2007 entitled "Toxicity Testing of the 21st Century: a Vision and a Strategy," significant advances within translational drug safety sciences promise to revolutionize drug discovery and development. The purpose of this review is to outline why investigative safety science is a competitive advantage for the pharmaceutical industry. The article discusses the essential goals for modern investigative toxicologists including: cross-species target biology; molecular pathways of toxicity; and development of predictive tools, models and biomarkers that allow discovery researchers and clinicians to anticipate safety problems and plan ways to address them, earlier than ever before. Furthermore, the article emphasizes the importance of investigating unanticipated clinical safety signals through a combination of mechanistic preclinical studies and/or molecular characterization of clinical samples from affected organs. The traditional boundaries between pharma industry teams focusing on safety/efficacy and preclinical/clinical development are rapidly disappearing in favor of translational safety science-centric organizations with a vision of bringing more effective medicines forward safely and quickly. Comparative biology and mechanistic toxicology approaches facilitate: i) identifying translational safety biomarkers; ii) identifying new drug targets/indications; and iii) mitigating off-target toxicities. These value-adding safety science contributions will change traditional toxicologists from side-effect identifiers to drug development enablers.

  10. Safety

    International Nuclear Information System (INIS)

    1998-01-01

    A brief account of activities carried out by the Nuclear power plants Jaslovske Bohunice in 1997 is presented. These activities are reported under the headings: (1) Nuclear safety; (2) Industrial and health safety; (3) Radiation safety; and Fire protection

  11. Translational Creativity

    DEFF Research Database (Denmark)

    Nielsen, Sandro

    2010-01-01

    A long-established approach to legal translation focuses on terminological equivalence making translators strictly follow the words of source texts. Recent research suggests that there is room for some creativity allowing translators to deviate from the source texts. However, little attention...... is given to genre conventions in source texts and the ways in which they can best be translated. I propose that translators of statutes with an informative function in expert-to-expert communication may be allowed limited translational creativity when translating specific types of genre convention....... This creativity is a result of translators adopting either a source-language or a target-language oriented strategy and is limited by the pragmatic principle of co-operation. Examples of translation options are provided illustrating the different results in target texts. The use of a target-language oriented...

  12. A decade of plant proteomics and mass spectrometry: translation of technical advancements to food security and safety issues.

    Science.gov (United States)

    Agrawal, Ganesh Kumar; Sarkar, Abhijit; Righetti, Pier Giorgio; Pedreschi, Romina; Carpentier, Sebastien; Wang, Tai; Barkla, Bronwyn J; Kohli, Ajay; Ndimba, Bongani Kaiser; Bykova, Natalia V; Rampitsch, Christof; Zolla, Lello; Rafudeen, Mohamed Suhail; Cramer, Rainer; Bindschedler, Laurence Veronique; Tsakirpaloglou, Nikolaos; Ndimba, Roya Janeen; Farrant, Jill M; Renaut, Jenny; Job, Dominique; Kikuchi, Shoshi; Rakwal, Randeep

    2013-01-01

    Tremendous progress in plant proteomics driven by mass spectrometry (MS) techniques has been made since 2000 when few proteomics reports were published and plant proteomics was in its infancy. These achievements include the refinement of existing techniques and the search for new techniques to address food security, safety, and health issues. It is projected that in 2050, the world's population will reach 9-12 billion people demanding a food production increase of 34-70% (FAO, 2009) from today's food production. Provision of food in a sustainable and environmentally committed manner for such a demand without threatening natural resources, requires that agricultural production increases significantly and that postharvest handling and food manufacturing systems become more efficient requiring lower energy expenditure, a decrease in postharvest losses, less waste generation and food with longer shelf life. There is also a need to look for alternative protein sources to animal based (i.e., plant based) to be able to fulfill the increase in protein demands by 2050. Thus, plant biology has a critical role to play as a science capable of addressing such challenges. In this review, we discuss proteomics especially MS, as a platform, being utilized in plant biology research for the past 10 years having the potential to expedite the process of understanding plant biology for human benefits. The increasing application of proteomics technologies in food security, analysis, and safety is emphasized in this review. But, we are aware that no unique approach/technology is capable to address the global food issues. Proteomics-generated information/resources must be integrated and correlated with other omics-based approaches, information, and conventional programs to ensure sufficient food and resources for human development now and in the future. © 2013 Wiley Periodicals, Inc.

  13. The EFFECT trial: evaluating exacerbations, biomarkers, and safety outcomes with two dose levels of fluticasone propionate/formoterol in COPD

    Directory of Open Access Journals (Sweden)

    Papi A

    2015-11-01

    Full Text Available Alberto Papi,1 Paul W Jones,2 Prashant S Dalvi,3 Kirsten McAulay,4 Tammy McIver,5 Sanjeeva Dissanayake3 1Department of Internal and CardioRespiratory Medicine, Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy; 2Institute for Infection and Immunity, St George’s, University of London, London, UK; 3Medical Science – Respiratory, 4Medical Operations, 5Data Management and Statistics, Mundipharma Research Ltd, Cambridge, UK Abstract: Inhaled corticosteroid/long-acting β2-agonist combination therapy is recommended in chronic obstructive pulmonary disease (COPD patients at high risk of exacerbations. The EFFECT (Efficacy of Fluticasone propionate/FormotErol in COPD Treatment trial is a Phase III, 52-week, randomized, double-blind study to evaluate the efficacy and safety of two doses of fluticasone propionate/formoterol compared to formoterol monotherapy in COPD patients with FEV1 ≤50% predicted and a history of exacerbations. The primary endpoint is the annualized rate of moderate and severe exacerbations. Secondary endpoints include pre-dose FEV1, EXACT-PRO (EXAcerbations of Chronic pulmonary disease Tool – Patient-Reported Outcome-defined exacerbations, St George’s Respiratory Questionnaire for COPD, COPD Assessment Test, and EXACT-Respiratory Symptoms total score. Lung-specific biomarkers (surfactant protein D and CC chemokine ligand-18 will be measured in a subset of patients to explore their relationship to other clinical indices in COPD and their predictive utility. Pneumonia will be diagnosed per criteria defined by the British Thoracic Society community acquired pneumonia guideline, primarily by radiological confirmation and, additionally, using clinical criteria when a chest radiograph cannot be obtained. Serial measurements of serum potassium, vital signs and electrocardiograms, 24-hour Holter monitoring, and 24-hour urinary cortisol measurement will be performed in a subset of patients in addition to

  14. Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment.

    Science.gov (United States)

    Chaudhari, Umesh; Nemade, Harshal; Wagh, Vilas; Gaspar, John Antonydas; Ellis, James K; Srinivasan, Sureshkumar Perumal; Spitkovski, Dimitry; Nguemo, Filomain; Louisse, Jochem; Bremer, Susanne; Hescheler, Jürgen; Keun, Hector C; Hengstler, Jan G; Sachinidis, Agapios

    2016-11-01

    The currently available techniques for the safety evaluation of candidate drugs are usually cost-intensive and time-consuming and are often insufficient to predict human relevant cardiotoxicity. The purpose of this study was to develop an in vitro repeated exposure toxicity methodology allowing the identification of predictive genomics biomarkers of functional relevance for drug-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The hiPSC-CMs were incubated with 156 nM doxorubicin, which is a well-characterized cardiotoxicant, for 2 or 6 days followed by washout of the test compound and further incubation in compound-free culture medium until day 14 after the onset of exposure. An xCELLigence Real-Time Cell Analyser was used to monitor doxorubicin-induced cytotoxicity while also monitoring functional alterations of cardiomyocytes by counting of the beating frequency of cardiomyocytes. Unlike single exposure, repeated doxorubicin exposure resulted in long-term arrhythmic beating in hiPSC-CMs accompanied by significant cytotoxicity. Global gene expression changes were studied using microarrays and bioinformatics tools. Analysis of the transcriptomic data revealed early expression signatures of genes involved in formation of sarcomeric structures, regulation of ion homeostasis and induction of apoptosis. Eighty-four significantly deregulated genes related to cardiac functions, stress and apoptosis were validated using real-time PCR. The expression of the 84 genes was further studied by real-time PCR in hiPSC-CMs incubated with daunorubicin and mitoxantrone, further anthracycline family members that are also known to induce cardiotoxicity. A panel of 35 genes was deregulated by all three anthracycline family members and can therefore be expected to predict the cardiotoxicity of compounds acting by similar mechanisms as doxorubicin, daunorubicin or mitoxantrone. The identified gene panel can be applied in the safety

  15. Machine Translation

    Indian Academy of Sciences (India)

    Research Mt System Example: The 'Janus' Translating Phone Project. The Janus ... based on laptops, and simultaneous translation of two speakers in a dialogue. For more ..... The current focus in MT research is on using machine learning.

  16. Stroke-Related Translational Research

    Science.gov (United States)

    Caplan, Louis R.; Arenillas, Juan; Cramer, Steven C.; Joutel, Anne; Lo, Eng H.; Meschia, James; Savitz, Sean; Tournier-Lasserve, Elizabeth

    2013-01-01

    Stroke-related translational research is multifaceted. Herein, we highlight genome-wide association studies and genetic studies of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, COL4A1 mutations, and cerebral cavernous malformations; advances in molecular biology and biomarkers; newer brain imaging research; and recovery from stroke emphasizing cell-based and other rehabilitative modalities. PMID:21555605

  17. Machine translation

    Energy Technology Data Exchange (ETDEWEB)

    Nagao, M

    1982-04-01

    Each language has its own structure. In translating one language into another one, language attributes and grammatical interpretation must be defined in an unambiguous form. In order to parse a sentence, it is necessary to recognize its structure. A so-called context-free grammar can help in this respect for machine translation and machine-aided translation. Problems to be solved in studying machine translation are taken up in the paper, which discusses subjects for semantics and for syntactic analysis and translation software. 14 references.

  18. SAFETY

    CERN Multimedia

    Niels Dupont

    2013-01-01

    CERN Safety rules and Radiation Protection at CMS The CERN Safety rules are defined by the Occupational Health & Safety and Environmental Protection Unit (HSE Unit), CERN’s institutional authority and central Safety organ attached to the Director General. In particular the Radiation Protection group (DGS-RP1) ensures that personnel on the CERN sites and the public are protected from potentially harmful effects of ionising radiation linked to CERN activities. The RP Group fulfils its mandate in collaboration with the CERN departments owning or operating sources of ionising radiation and having the responsibility for Radiation Safety of these sources. The specific responsibilities concerning "Radiation Safety" and "Radiation Protection" are delegated as follows: Radiation Safety is the responsibility of every CERN Department owning radiation sources or using radiation sources put at its disposition. These Departments are in charge of implementing the requi...

  19. Translating India

    CERN Document Server

    Kothari, Rita

    2014-01-01

    The cultural universe of urban, English-speaking middle class in India shows signs of growing inclusiveness as far as English is concerned. This phenomenon manifests itself in increasing forms of bilingualism (combination of English and one Indian language) in everyday forms of speech - advertisement jingles, bilingual movies, signboards, and of course conversations. It is also evident in the startling prominence of Indian Writing in English and somewhat less visibly, but steadily rising, activity of English translation from Indian languages. Since the eighties this has led to a frenetic activity around English translation in India's academic and literary circles. Kothari makes this very current phenomenon her chief concern in Translating India.   The study covers aspects such as the production, reception and marketability of English translation. Through an unusually multi-disciplinary approach, this study situates English translation in India amidst local and global debates on translation, representation an...

  20. Translating Inclusion

    DEFF Research Database (Denmark)

    Fallov, Mia Arp; Birk, Rasmus

    2018-01-01

    The purpose of this paper is to explore how practices of translation shape particular paths of inclusion for people living in marginalized residential areas in Denmark. Inclusion, we argue, is not an end-state, but rather something which must be constantly performed. Active citizenship, today......, is not merely a question of participation, but of learning to become active in all spheres of life. The paper draws on empirical examples from a multi-sited field work in 6 different sites of local community work in Denmark, to demonstrate how different dimensions of translation are involved in shaping active...... citizenship. We propose the following different dimensions of translation: translating authority, translating language, translating social problems. The paper takes its theoretical point of departure from assemblage urbanism, arguing that cities are heterogeneous assemblages of socio-material interactions...

  1. Pharmacogenomic Biomarkers

    Directory of Open Access Journals (Sweden)

    Sandra C. Kirkwood

    2002-01-01

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

  2. Diagnostic and prognostic epigenetic biomarkers in cancer.

    Science.gov (United States)

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

    2015-01-01

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

  3. Safety

    International Nuclear Information System (INIS)

    2001-01-01

    This annual report of the Senior Inspector for the Nuclear Safety, analyses the nuclear safety at EDF for the year 1999 and proposes twelve subjects of consideration to progress. Five technical documents are also provided and discussed concerning the nuclear power plants maintenance and safety (thermal fatigue, vibration fatigue, assisted control and instrumentation of the N4 bearing, 1300 MW reactors containment and time of life of power plants). (A.L.B.)

  4. Compositional translation

    NARCIS (Netherlands)

    Appelo, Lisette; Janssen, Theo; Jong, de F.M.G.; Landsbergen, S.P.J.

    1994-01-01

    This book provides an in-depth review of machine translation by discussing in detail a particular method, called compositional translation, and a particular system, Rosetta, which is based on this method. The Rosetta project is a unique combination of fundamental research and large-scale

  5. Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts.

    Science.gov (United States)

    Thulin, Petra; Nordahl, Gunnar; Gry, Marcus; Yimer, Getnet; Aklillu, Eleni; Makonnen, Eyasu; Aderaye, Getachew; Lindquist, Lars; Mattsson, C Mikael; Ekblom, Björn; Antoine, Daniel J; Park, B Kevin; Linder, Stig; Harrill, Alison H; Watkins, Paul B; Glinghammar, Björn; Schuppe-Koistinen, Ina

    2014-03-01

    There is a demand for more sensitive, specific and predictive biomarkers for drug-induced liver injury (DILI) than the gold standard used today, alanine aminotransferase (ALT). The aim of this study was to qualify novel DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate dehydrogenase and alpha-foetoprotein) in human DILI. Levels of the novel biomarkers were measured by enzyme-linked immunosorbent assay or real-time quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a human volunteer study with acetaminophen and a human immunodeficiency virus (HIV)/tuberculosis (TB) study. In the acetaminophen study, serum M65 and microRNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased after 1 week of treatment. In contrast to ALT, the novel biomarkers remained stable in a human cohort with exercise-induced muscular injury. M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Translational plant proteomics: a perspective.

    Science.gov (United States)

    Agrawal, Ganesh Kumar; Pedreschi, Romina; Barkla, Bronwyn J; Bindschedler, Laurence Veronique; Cramer, Rainer; Sarkar, Abhijit; Renaut, Jenny; Job, Dominique; Rakwal, Randeep

    2012-08-03

    Translational proteomics is an emerging sub-discipline of the proteomics field in the biological sciences. Translational plant proteomics aims to integrate knowledge from basic sciences to translate it into field applications to solve issues related but not limited to the recreational and economic values of plants, food security and safety, and energy sustainability. In this review, we highlight the substantial progress reached in plant proteomics during the past decade which has paved the way for translational plant proteomics. Increasing proteomics knowledge in plants is not limited to model and non-model plants, proteogenomics, crop improvement, and food analysis, safety, and nutrition but to many more potential applications. Given the wealth of information generated and to some extent applied, there is the need for more efficient and broader channels to freely disseminate the information to the scientific community. This article is part of a Special Issue entitled: Translational Proteomics. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Binary translation using peephole translation rules

    Science.gov (United States)

    Bansal, Sorav; Aiken, Alex

    2010-05-04

    An efficient binary translator uses peephole translation rules to directly translate executable code from one instruction set to another. In a preferred embodiment, the translation rules are generated using superoptimization techniques that enable the translator to automatically learn translation rules for translating code from the source to target instruction set architecture.

  8. Precision translator

    Science.gov (United States)

    Reedy, Robert P.; Crawford, Daniel W.

    1984-01-01

    A precision translator for focusing a beam of light on the end of a glass fiber which includes two turning fork-like members rigidly connected to each other. These members have two prongs each with its separation adjusted by a screw, thereby adjusting the orthogonal positioning of a glass fiber attached to one of the members. This translator is made of simple parts with capability to keep adjustment even in condition of rough handling.

  9. Translational Educational Research

    Science.gov (United States)

    Issenberg, S. Barry; Cohen, Elaine R.; Barsuk, Jeffrey H.; Wayne, Diane B.

    2012-01-01

    Medical education research contributes to translational science (TS) when its outcomes not only impact educational settings, but also downstream results, including better patient-care practices and improved patient outcomes. Simulation-based medical education (SBME) has demonstrated its role in achieving such distal results. Effective TS also encompasses implementation science, the science of health-care delivery. Educational, clinical, quality, and safety goals can only be achieved by thematic, sustained, and cumulative research programs, not isolated studies. Components of an SBME TS research program include motivated learners, curriculum grounded in evidence-based learning theory, educational resources, evaluation of downstream results, a productive research team, rigorous research methods, research resources, and health-care system acceptance and implementation. National research priorities are served from translational educational research. National funding priorities should endorse the contribution and value of translational education research. PMID:23138127

  10. Machine Translation and Other Translation Technologies.

    Science.gov (United States)

    Melby, Alan

    1996-01-01

    Examines the application of linguistic theory to machine translation and translator tools, discusses the use of machine translation and translator tools in the real world of translation, and addresses the impact of translation technology on conceptions of language and other issues. Findings indicate that the human mind is flexible and linguistic…

  11. Translation Competence

    DEFF Research Database (Denmark)

    Vandepitte, Sonia; Mousten, Birthe; Maylath, Bruce

    2014-01-01

    After Kiraly (2000) introduced the collaborative form of translation in classrooms, Pavlovic (2007), Kenny (2008), and Huertas Barros (2011) provided empirical evidence that testifies to the impact of collaborative learning. This chapter sets out to describe the collaborative forms of learning at...

  12. Translating Harbourscapes

    DEFF Research Database (Denmark)

    Diedrich, Lisa Babette

    -specific design are proposed for all actors involved in harbour transformation. The study ends with an invitation to further investigate translation as a powerful metaphor for the way existing qualities of a site can be transformed, rather than erased or rewritten, and to explore how this metaphor can foster new...

  13. Word translation entropy in translation

    DEFF Research Database (Denmark)

    Schaeffer, Moritz; Dragsted, Barbara; Hvelplund, Kristian Tangsgaard

    2016-01-01

    This study reports on an investigation into the relationship between the number of translation alternatives for a single word and eye movements on the source text. In addition, the effect of word order differences between source and target text on eye movements on the source text is studied....... In particular, the current study investigates the effect of these variables on early and late eye movement measures. Early eye movement measures are indicative of processes that are more automatic while late measures are more indicative of conscious processing. Most studies that found evidence of target...... language activation during source text reading in translation, i.e. co-activation of the two linguistic systems, employed late eye movement measures or reaction times. The current study therefore aims to investigate if and to what extent earlier eye movement measures in reading for translation show...

  14. Effect of consuming a purple-fleshed sweet potato beverage on health-related biomarkers and safety parameters in Caucasian subjects with elevated levels of blood pressure and liver function biomarkers: a 4-week, open-label, non-comparative trial.

    Science.gov (United States)

    Oki, Tomoyuki; Kano, Mitsuyoshi; Watanabe, Osamu; Goto, Kazuhisa; Boelsma, Esther; Ishikawa, Fumiyasu; Suda, Ikuo

    2016-01-01

    An open-label study with one treatment arm was conducted to investigate changes in health-related biomarkers (blood pressure and liver enzyme activity) and the safety of 4 weeks of consuming a purple-fleshed sweet potato beverage in Caucasian subjects. Twenty healthy adults, 18-70 years of age, with a body mass index >25 kg/m(2), elevated blood pressure and elevated levels of liver function biomarkers consumed two cartons of purple-fleshed sweet potato beverage (125 ml, including 117 mg anthocyanin per carton) daily for 4 weeks. Hematology, serum clinical profile, dipstick urinalysis and blood pressure were determined before consumption, at 2 and 4 weeks of consumption and after a 2-week washout period. A trend was found toward lowering systolic blood pressure during the treatment period (p=0.0590). No significant changes were found in diastolic blood pressure throughout the study period. Systolic blood pressure was significantly lower after 4 weeks of consumption compared with before consumption (p=0.0125) and was significantly higher after the 2-week washout period compared with after consumption (p=0.0496). The serum alanine aminotransferase level significantly increased over time, but aspartate aminotransferase and γ-glutamyltransferase levels stayed within the normal range of reference values. Safety parameters of the blood and urine showed no clinically relevant changes. The consumption of a purple-fleshed sweet potato beverage for 4 weeks resulted in no clinically relevant changes in safety parameters of the blood and urine and showed a trend toward lowering systolic blood pressure.

  15. SAFETY

    CERN Multimedia

    M. Plagge, C. Schaefer and N. Dupont

    2013-01-01

    Fire Safety – Essential for a particle detector The CMS detector is a marvel of high technology, one of the most precise particle measurement devices we have built until now. Of course it has to be protected from external and internal incidents like the ones that can occur from fires. Due to the fire load, the permanent availability of oxygen and the presence of various ignition sources mostly based on electricity this has to be addressed. Starting from the beam pipe towards the magnet coil, the detector is protected by flooding it with pure gaseous nitrogen during operation. The outer shell of CMS, namely the yoke and the muon chambers are then covered by an emergency inertion system also based on nitrogen. To ensure maximum fire safety, all materials used comply with the CERN regulations IS 23 and IS 41 with only a few exceptions. Every piece of the 30-tonne polyethylene shielding is high-density material, borated, boxed within steel and coated with intumescent (a paint that creates a thick co...

  16. SAFETY

    CERN Multimedia

    C. Schaefer and N. Dupont

    2013-01-01

      “Safety is the highest priority”: this statement from CERN is endorsed by the CMS management. An interpretation of this statement may bring you to the conclusion that you should stop working in order to avoid risks. If the safety is the priority, work is not! This would be a misunderstanding and misinterpretation. One should understand that “working safely” or “operating safely” is the priority at CERN. CERN personnel are exposed to different hazards on many levels on a daily basis. However, risk analyses and assessments are done in order to limit the number and the gravity of accidents. For example, this process takes place each time you cross the road. The hazard is the moving vehicle, the stake is you and the risk might be the risk of collision between both. The same principle has to be applied during our daily work. In particular, keeping in mind the general principles of prevention defined in the late 1980s. These principles wer...

  17. Translational genomics

    Directory of Open Access Journals (Sweden)

    Martin Kussmann

    2014-09-01

    Full Text Available The term “Translational Genomics” reflects both title and mission of this new journal. “Translational” has traditionally been understood as “applied research” or “development”, different from or even opposed to “basic research”. Recent scientific and societal developments have triggered a re-assessment of the connotation that “translational” and “basic” are either/or activities: translational research nowadays aims at feeding the best science into applications and solutions for human society. We therefore argue here basic science to be challenged and leveraged for its relevance to human health and societal benefits. This more recent approach and attitude are catalyzed by four trends or developments: evidence-based solutions; large-scale, high dimensional data; consumer/patient empowerment; and systems-level understanding.

  18. Beyond Translation

    DEFF Research Database (Denmark)

    Olwig, Mette Fog

    2013-01-01

    This article contributes to the growing scholarship on local development practitioners by re-examining conceptualizations of practitioners as ‘brokers’ strategically translating between ‘travelling’ (development institution) rationalities and ‘placed’ (recipient area) rationalities in relation...... and practice spurred by new challenges deriving from climate change anxiety, the study shows how local practitioners often make local activities fit into travelling development rationalities as a matter of habit, rather than as a conscious strategy. They may therefore cease to ‘translate’ between different...... rationalities. This is shown to have important implications for theory, research and practice concerning disaster risk reduction and climate change adaptation in which such translation is often expected....

  19. Revising Translations

    DEFF Research Database (Denmark)

    Rasmussen, Kirsten Wølch; Schjoldager, Anne

    2011-01-01

    The paper explains the theoretical background and findings of an empirical study of revision policies, using Denmark as a case in point. After an overview of important definitions, types and parameters, the paper explains the methods and data gathered from a questionnaire survey and an interview...... survey. Results clearly show that most translation companies regard both unilingual and comparative revisions as essential components of professional quality assurance. Data indicate that revision is rarely fully comparative, as the preferred procedure seems to be a unilingual revision followed by a more...... or less comparative rereading. Though questionnaire data seem to indicate that translation companies use linguistic correctness and presentation as the only revision parameters, interview data reveal that textual and communicative aspects are also considered. Generally speaking, revision is not carried...

  20. Safety

    International Nuclear Information System (INIS)

    Jones, P.M.S.

    1987-01-01

    Aspects of fission reactors are considered - control, heat removal and containment. Brief descriptions of the reactor accidents at the SL-1 reactor (1961), Windscale (1957), Browns Ferry (1975), Three Mile Island (1979) and Chernobyl (1986) are given. The idea of inherently safe reactor designs is discussed. Safety assessment is considered under the headings of preliminary hazard analysis, failure mode analysis, event trees, fault trees, common mode failure and probabalistic risk assessments. These latter can result in a series of risk distributions linked to specific groups of fault sequences and specific consequences. A frequency-consequence diagram is shown. Fatal accident incidence rates in different countries including the United Kingdom for various industries are quoted. The incidence of fatal cancers from occupational exposure to chemicals is tabulated. Human factors and the acceptability of risk are considered. (U.K.)

  1. Ebola: translational science considerations.

    Science.gov (United States)

    Chiappelli, Francesco; Bakhordarian, Andre; Thames, April D; Du, Angela M; Jan, Allison L; Nahcivan, Melissa; Nguyen, Mia T; Sama, Nateli; Manfrini, Ercolano; Piva, Francesco; Rocha, Rafael Malagoli; Maida, Carl A

    2015-01-16

    We are currently in the midst of the most aggressive and fulminating outbreak of Ebola-related disease, commonly referred to as "Ebola", ever recorded. In less than a year, the Ebola virus (EBOV, Zaire ebolavirus species) has infected over 10,000 people, indiscriminately of gender or age, with a fatality rate of about 50%. Whereas at its onset this Ebola outbreak was limited to three countries in West Africa (Guinea, where it was first reported in late March 2014, Liberia, where it has been most rampant in its capital city, Monrovia and other metropolitan cities, and Sierra Leone), cases were later reported in Nigeria, Mali and Senegal, as well as in Western Europe (i.e., Madrid, Spain) and the US (i.e., Dallas, Texas; New York City) by late October 2014. World and US health agencies declared that the current Ebola virus disease (EVD) outbreak has a strong likelihood of growing exponentially across the world before an effective vaccine, treatment or cure can be developed, tested, validated and distributed widely. In the meantime, the spread of the disease may rapidly evolve from an epidemics to a full-blown pandemic. The scientific and healthcare communities actively research and define an emerging kaleidoscope of knowledge about critical translational research parameters, including the virology of EBOV, the molecular biomarkers of the pathological manifestations of EVD, putative central nervous system involvement in EVD, and the cellular immune surveillance to EBOV, patient-centered anthropological and societal parameters of EVD, as well as translational effectiveness about novel putative patient-targeted vaccine and pharmaceutical interventions, which hold strong promise, if not hope, to curb this and future Ebola outbreaks. This work reviews and discusses the principal known facts about EBOV and EVD, and certain among the most interesting ongoing or future avenues of research in the field, including vaccination programs for the wild animal vectors of the virus

  2. Outline of the report on the seismic safety examination of nuclear facilities based on the 1995 Hyogoken-Nanbu earthquake (tentative translation) - September 1995

    International Nuclear Information System (INIS)

    2003-01-01

    From the standpoint of thoroughly confirming the seismic safety of nuclear facilities, Nuclear Safety Commission established an Examination Committee on the Seismic Safety of Nuclear Power Reactor Facilities (hereinafter called Seismic Safety Examination Committee) based on the 1995 Hyogoken-Nanbu Earthquake on January 19, 1995, two days after the occurrence of the earthquake, in order to examine the validity of related guidelines on the seismic design to be used for the safety examination. This report outlines the results of the examinations by the Seismic Safety Examination Committee: basic principle of examinations at the seismic safety examination committee, overview on the related guidelines of the seismic design, information and knowledge obtained on the 1995 Hyogoken-Nanbu earthquake, examination of validity of the guidelines based on various information of the Hyogoken-Nanbu earthquake. The Seismic Design Examination Committee surveyed the related guidelines on seismic design, selected the items to be examined, and examined on those items based on the knowledge obtained from the Hyogoken-Nanbu Earthquake. As a result, the Committee confirmed that the validity of the guidelines regulating the seismic design of nuclear facilities is not impaired even though on the basis of the Hyogoken-Nanbu Earthquake. However, the people related to the nuclear facilities may not be content with the above result, but continuously put efforts in doing the following matters to improve furthermore the reliability of seismic design of nuclear facilities by always reflecting the latest knowledge on the seismic design. 1) - The people related to nuclear facilities must seriously accept the fact that valuable knowledge could be obtained from the Hyogoken-Nanbu Earthquake, try to study and analyze the obtained data, and reflect the results of investigations, studies, and examinations conducted appropriately to the seismic design of nuclear facilities referring to the investigations

  3. Biomarker discovery and applications for foods and beverages: proteomics to nanoproteomics.

    Science.gov (United States)

    Agrawal, Ganesh Kumar; Timperio, Anna Maria; Zolla, Lello; Bansal, Vipul; Shukla, Ravi; Rakwal, Randeep

    2013-11-20

    Foods and beverages have been at the heart of our society for centuries, sustaining humankind - health, life, and the pleasures that go with it. The more we grow and develop as a civilization, the more we feel the need to know about the food we eat and beverages we drink. Moreover, with an ever increasing demand for food due to the growing human population food security remains a major concern. Food safety is another growing concern as the consumers prefer varied foods and beverages that are not only traded nationally but also globally. The 21st century science and technology is at a new high, especially in the field of biological sciences. The availability of genome sequences and associated high-throughput sensitive technologies means that foods are being analyzed at various levels. For example and in particular, high-throughput omics approaches are being applied to develop suitable biomarkers for foods and beverages and their applications in addressing quality, technology, authenticity, and safety issues. Proteomics are one of those technologies that are increasingly being utilized to profile expressed proteins in different foods and beverages. Acquired knowledge and protein information have now been translated to address safety of foods and beverages. Very recently, the power of proteomic technology has been integrated with another highly sensitive and miniaturized technology called nanotechnology, yielding a new term nanoproteomics. Nanoproteomics offer a real-time multiplexed analysis performed in a miniaturized assay, with low-sample consumption and high sensitivity. To name a few, nanomaterials - quantum dots, gold nanoparticles, carbon nanotubes, and nanowires - have demonstrated potential to overcome the challenges of sensitivity faced by proteomics for biomarker detection, discovery, and application. In this review, we will discuss the importance of biomarker discovery and applications for foods and beverages, the contribution of proteomic technology in

  4. Lost in Translation? Challenges and Opportunities for Raising Health and Safety Awareness among a Multinational Workforce in the United Arab Emirates

    Science.gov (United States)

    Cooling, Robert Fletcher; Aw, Tar-Ching

    2012-01-01

    The United Arab Emirates (UAE) has experienced tremendous economic and industrial growth in the petroleum, airline, maritime and construction sectors, especially since the discovery of oil reserves. Mass recruitment of low skilled or unskilled laborers from less-developed countries has been utilized to satisfy the manpower demands of these fast paced industrial developments. Such workforce recruitment has created an unusual populace demographic, with the total UAE population estimated at 8.3 million, composed of 950,000 Emiratis, with the remainder being multinational expatriate workers, with varying educational qualifications, work experience, religious beliefs, cultural practices, and native languages. These unique characteristics pose a challenge for health and safety professionals tasked with ensuring the UAE workforce adheres to specific occupational health and safety procedures. The paper discusses two case studies that employ a novel multimedia approach to raising health and safety awareness among a multinational workforce. PMID:23251846

  5. Biomarkers in psoriasis and psoriatic arthritis.

    Science.gov (United States)

    Villanova, Federica; Di Meglio, Paola; Nestle, Frank O

    2013-04-01

    Psoriasis is a common immune-mediated disease of the skin, which associates in 20-30% of patients with psoriatic arthritis (PsA). The immunopathogenesis of both conditions is not fully understood as it is the result of a complex interaction between genetic, environmental and immunological factors. At present there is no cure for psoriasis and there are no specific markers that can accurately predict disease progression and therapeutic response. Therefore, biomarkers for disease prognosis and response to treatment are urgently needed to help clinicians with objective indications to improve patient management and outcomes. Although many efforts have been made to identify psoriasis/PsA biomarkers none of them has yet been translated into routine clinical practice. In this review we summarise the different classes of possible biomarkers explored in psoriasis and PsA so far and discuss novel strategies for biomarker discovery.

  6. Translating democracy

    DEFF Research Database (Denmark)

    Doerr, Nicole

    2012-01-01

    Linguistic barriers may pose problems for politicians trying to communicate delicate decisions to a European-wide public, as well as for citizens wishing to protest at the European level. In this article I present a counter-intuitive position on the language question, one that explores how...... Forum (ESF). I compare deliberative practices in the multilingual ESF preparatory meetings with those in monolingual national Social Forum meetings in three Western European countries. My comparison shows that multilingualism does not reduce the inclusivity of democratic deliberation as compared...... in institutionalized habits and norms of deliberation. Addressing democratic theorists, my findings suggest that translation could be a way to think about difference not as a hindrance but as a resource for democracy in linguistically heterogeneous societies and public spaces, without presupposing a shared language...

  7. Translator's preface.

    Science.gov (United States)

    Lamiell, James T

    2013-08-01

    Presents a preface from James T. Lamiell, who translates Wilhelm Wundt's Psychology's Struggle for Existence (Die Psychologie im Kampf ums Dasein), in which Wundt advised against the impending divorce of psychology from philosophy, into English. Lamiell comments that more than a decade into the 21st century, it appears that very few psychologists have any interest at all in work at the interface of psychology and philosophy. He notes that one clear indication of this is that the Society for Theoretical and Philosophical Psychology, which is Division 24 of the American Psychological Association (APA), remains one of the smallest of the APA's nearly 60 divisions. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  8. Biomarkers: Delivering on the expectation of molecularly driven, quantitative health.

    Science.gov (United States)

    Wilson, Jennifer L; Altman, Russ B

    2018-02-01

    Biomarkers are the pillars of precision medicine and are delivering on expectations of molecular, quantitative health. These features have made clinical decisions more precise and personalized, but require a high bar for validation. Biomarkers have improved health outcomes in a few areas such as cancer, pharmacogenetics, and safety. Burgeoning big data research infrastructure, the internet of things, and increased patient participation will accelerate discovery in the many areas that have not yet realized the full potential of biomarkers for precision health. Here we review themes of biomarker discovery, current implementations of biomarkers for precision health, and future opportunities and challenges for biomarker discovery. Impact statement Precision medicine evolved because of the understanding that human disease is molecularly driven and is highly variable across patients. This understanding has made biomarkers, a diverse class of biological measurements, more relevant for disease diagnosis, monitoring, and selection of treatment strategy. Biomarkers' impact on precision medicine can be seen in cancer, pharmacogenomics, and safety. The successes in these cases suggest many more applications for biomarkers and a greater impact for precision medicine across the spectrum of human disease. The authors assess the status of biomarker-guided medical practice by analyzing themes for biomarker discovery, reviewing the impact of these markers in the clinic, and highlight future and ongoing challenges for biomarker discovery. This work is timely and relevant, as the molecular, quantitative approach of precision medicine is spreading to many disease indications.

  9. Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

    Science.gov (United States)

    Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

    2016-12-12

    The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

  10. Mapping Translation Technology Research in Translation Studies

    DEFF Research Database (Denmark)

    Schjoldager, Anne; Christensen, Tina Paulsen; Flanagan, Marian

    2017-01-01

    section aims to improve this situation by presenting new and innovative research papers that reflect on recent technological advances and their impact on the translation profession and translators from a diversity of perspectives and using a variety of methods. In Section 2, we present translation......Due to the growing uptake of translation technology in the language industry and its documented impact on the translation profession, translation students and scholars need in-depth and empirically founded knowledge of the nature and influences of translation technology (e.g. Christensen....../Schjoldager 2010, 2011; Christensen 2011). Unfortunately, the increasing professional use of translation technology has not been mirrored within translation studies (TS) by a similar increase in research projects on translation technology (Munday 2009: 15; O’Hagan 2013; Doherty 2016: 952). The current thematic...

  11. Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment

    NARCIS (Netherlands)

    Chaudhari, U.; Nemade, H.; Wagh, V.; Ellis, J.K.; Srinivasan, S.; Louisse, J.

    2016-01-01

    The currently available techniques for the safety evaluation of candidate drugs are usually cost-intensive and time-consuming and are often insufficient to predict human relevant cardiotoxicity. The purpose of this study was to develop an in vitro repeated exposure toxicity methodology allowing the

  12. Adaptação transcultural da versão brasileira do Hospital Survey on Patient Safety Culture: etapa inicial Translation and cross-cultural adaptation of the Brazilian version of the Hospital Survey on Patient Safety Culture: initial stage

    Directory of Open Access Journals (Sweden)

    Claudia Tartaglia Reis

    2012-11-01

    Full Text Available A avaliação da cultura de segurança do paciente permite aos hospitais identificar e gerir prospectivamente questões relevantes de segurança em suas rotinas de trabalho. Este artigo descreve a adaptação transcultural do Hospital Survey on Patient Safety Culture (HSOPSC para a Língua Portuguesa e contexto brasileiro. Adotou-se abordagem universalista para avaliar a equivalência conceitual, de itens e semântica. A metodologia incluiu os seguintes estágios: (1 tradução do questionário para o Português; (2 retradução para o Inglês; (3 painel de especialistas para elaboração da versão preliminar; (4 avaliação da compreensão verbal pela população-alvo. O questionário foi traduzido para o Português e sua versão final incluiu 42 itens. A população-alvo avaliou todos os itens como de fácil compreensão. O questionário encontra-se traduzido para o Português e adaptado para o contexto brasileiro, entretanto, faz-se necessário avaliar sua equivalência de mensuração, validade externa e reprodutibilidade.Patient safety culture assessment allows hospitals to identify and prospectively manage safety issues in work routines. This article aimed to describe the cross-cultural adaptation of the Hospital Survey on Patient Safety Culture (HSOPSC into Brazilian Portuguese. A universalist approach was adopted to assess conceptual, item, and semantic equivalence. The methodology involved the following stages: (1 translation of the questionnaire into Portuguese; (2 back-translation into English; (3 an expert panel to prepare a draft version; and (4 assessment of verbal understanding of the draft by a sample of the target population. The questionnaire was translated into Portuguese, and the scale's final version included 42 items. The target population sample assessed all the items as easy to understand. The questionnaire has been translated into Portuguese and adapted to the Brazilian hospital context, but it is necessary to assess

  13. Biomarkers for equine joint injury and osteoarthritis.

    Science.gov (United States)

    McIlwraith, C Wayne; Kawcak, Christopher E; Frisbie, David D; Little, Christopher B; Clegg, Peter D; Peffers, Mandy J; Karsdal, Morten A; Ekman, Stina; Laverty, Sheila; Slayden, Richard A; Sandell, Linda J; Lohmander, L S; Kraus, Virginia B

    2018-03-01

    We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bone failure in equine athletes. The workshop was attended by leading scientists in the fields of equine and human musculoskeletal biomarkers to enable cross-disciplinary exchange and improve knowledge in both. Detailed proceedings with strategic planning was written, added to, edited and referenced to develop this manuscript. The most recent information from work in equine and human osteoarthritic biomarkers was accumulated, including the use of personalized healthcare to stratify OA phenotypes, transcriptome analysis of anterior cruciate ligament (ACL) and meniscal injuries in the human knee. The spectrum of "wet" biomarker assays that are antibody based that have achieved usefulness in both humans and horses, imaging biomarkers and the role they can play in equine and human OA was discussed. Prediction of musculoskeletal injury in the horse remains a challenge, and the potential usefulness of spectroscopy, metabolomics, proteomics, and development of biobanks to classify biomarkers in different stages of equine and human OA were reviewed. The participants concluded that new information and studies in equine musculoskeletal biomarkers have potential translational value for humans and vice versa. OA is equally important in humans and horses, and the welfare issues associated with catastrophic musculoskeletal injury in horses add further emphasis to the need for good validated biomarkers in the horse. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:823-831, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  14. A translational approach to evaluate the efficacy and safety of the novel AMPA receptor positive allosteric modulator org 26576 in adult attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Adler, Lenard A; Kroon, René A; Stein, Mark; Shahid, Mohammed; Tarazi, Frank I; Szegedi, Armin; Schipper, Jacques; Cazorla, Pilar

    2012-12-01

    It has been posited that glutamate dysregulation contributes to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Modulation of glutamate neurotransmission may provide alternative therapeutic options. The novel 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptor positive allosteric modulator Org 26576 was investigated with a translational approach including preclinical and clinical testing. Neonatal rat 6-hydroxydopamine lesion-induced hyperactivity was used as preclinical model. Seventy-eight ADHD adults entered a multicenter, double-blind, placebo-controlled, two-period crossover trial. After 1 week placebo lead-in, 67 subjects were randomized into one of four treatment sequences: sequence A (n = 15) Org 26576 (100 mg b.i.d.) for 3 weeks, followed by a 2-week placebo crossover and 3 weeks placebo; sequence B (n = 16) 5 weeks placebo followed by 3 weeks Org 26576 (100 mg b.i.d.); sequence C (n = 18) Org 26576 flexible dose (100-300 mg b.i.d.) for 3 weeks, then 5 weeks placebo; sequence D (n = 18) 5 weeks placebo followed by 3 weeks Org 26576 (100-300 mg b.i.d.). The Adult ADHD Investigator Symptom Rating Scale was used to assess changes in ADHD symptomatology. Org 26576 (1, 3, 10 mg/kg intraperitoneal) produced dose-dependent inhibition of locomotor hyperactivity in 6-hydroxydopamine-lesioned rats. Org 26576 (100 mg b.i.d.) was superior to placebo in treating symptoms of adult ADHD subjects. The primary Adult ADHD Investigator Symptom Rating Scale results were supported by some secondary analyses. However, Org 26576 (100-300 mg b.i.d.) did not confirm these results. Most frequently reported adverse events were nausea, dizziness, and headache. These preclinical and clinical findings suggest that Org 25676 may have utility in the treatment of ADHD. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes

    International Nuclear Information System (INIS)

    Moser, Virginia C.; Stewart, Nicholas; Freeborn, Danielle L.; Crooks, James; MacMillan, Denise K.; Hedge, Joan M.; Wood, Charles E.; McMahen, Rebecca L.; Strynar, Mark J.; Herr, David W.

    2015-01-01

    There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects), singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics

  16. Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes

    Energy Technology Data Exchange (ETDEWEB)

    Moser, Virginia C., E-mail: Moser.ginger@epa.gov [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Stewart, Nicholas; Freeborn, Danielle L. [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Crooks, James; MacMillan, Denise K. [Analytical Chemistry Research Core/Research Cores Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hedge, Joan M.; Wood, Charles E. [Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); McMahen, Rebecca L. [ORISE fellow, Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Strynar, Mark J. [Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Herr, David W. [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2015-01-15

    There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects), singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics

  17. Mapping Translation Technology Research in Translation Studies

    DEFF Research Database (Denmark)

    Schjoldager, Anne; Christensen, Tina Paulsen; Flanagan, Marian

    2017-01-01

    /Schjoldager 2010, 2011; Christensen 2011). Unfortunately, the increasing professional use of translation technology has not been mirrored within translation studies (TS) by a similar increase in research projects on translation technology (Munday 2009: 15; O’Hagan 2013; Doherty 2016: 952). The current thematic...... section aims to improve this situation by presenting new and innovative research papers that reflect on recent technological advances and their impact on the translation profession and translators from a diversity of perspectives and using a variety of methods. In Section 2, we present translation...... technology research as a subdiscipline of TS, and we define and discuss some basic concepts and models of the field that we use in the rest of the paper. Based on a small-scale study of papers published in TS journals between 2006 and 2016, Section 3 attempts to map relevant developments of translation...

  18. Translational environmental biology: cell biology informing conservation.

    Science.gov (United States)

    Traylor-Knowles, Nikki; Palumbi, Stephen R

    2014-05-01

    Typically, findings from cell biology have been beneficial for preventing human disease. However, translational applications from cell biology can also be applied to conservation efforts, such as protecting coral reefs. Recent efforts to understand the cell biological mechanisms maintaining coral health such as innate immunity and acclimatization have prompted new developments in conservation. Similar to biomedicine, we urge that future efforts should focus on better frameworks for biomarker development to protect coral reefs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Combination of biomarkers

    DEFF Research Database (Denmark)

    Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger

    2012-01-01

    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....

  20. Lost in translation: The challenge of adapting integrated approaches for worker health and safety for low- and middle-income countries.

    Directory of Open Access Journals (Sweden)

    Glorian Sorensen

    Full Text Available To describe the process of adapting an intervention integrating occupational safety and health (OSH and health promotion for manufacturing worksites in India and the challenges faced in implementing it; and explore how globalization trends may influence the implementation of these integrated approaches in India and other low- and middle-income countries (LMICs.This study-conducted in 22 manufacturing worksites in Mumbai, India-adapted and implemented an evidence-based intervention tested in the U.S. that integrated OSH and tobacco control. The systematic adaptation process included formative research and pilot testing, to ensure that the tested intervention was tailored to the local setting. We used qualitative methods and process evaluation to assess the extent to which this intervention was implemented, and to explore barriers to implementation.While participating worksites agreed to implement this intervention, not all components of the adapted intervention were implemented fully in the 10 worksites assigned to the intervention condition. We found that the OSH infrastructure in India focused predominantly on regulatory compliance, medical screening (secondary prevention and the treatment of injuries. We observed generally low levels of leadership support and commitment to OSH, evidenced by minimal management participation in the intervention, reluctance to discuss OSH issues with the study team or workers, and little receptivity to recommendations resulting from the industrial hygienist's reports.India presents one example of a LMIC with a rising burden of non-communicable diseases and intensified exposures to both physical and organizational hazards on the job. Our experiences highlight the importance of national and global trends that shape workers' experiences on the job and their related health outcomes. Beyond a singular focus on prevention of non-communicable diseases, coordinated national and international efforts are needed to address

  1. Nanomaterials based biosensors for cancer biomarker detection

    International Nuclear Information System (INIS)

    Malhotra, Bansi D; Kumar, Saurabh; Pandey, Chandra Mouli

    2016-01-01

    Biosensors have enormous potential to contribute to the evolution of new molecular diagnostic techniques for patients suffering with cancerous diseases. A major obstacle preventing faster development of biosensors pertains to the fact that cancer is a highly complex set of diseases. The oncologists currently rely on a few biomarkers and histological characterization of tumors. Some of the signatures include epigenetic and genetic markers, protein profiles, changes in gene expression, and post-translational modifications of proteins. These molecular signatures offer new opportunities for development of biosensors for cancer detection. In this context, conducting paper has recently been found to play an important role towards the fabrication of a biosensor for cancer biomarker detection. In this paper we will focus on results of some of the recent studies obtained in our laboratories relating to fabrication and application of nanomaterial modified paper based biosensors for cancer biomarker detection. (paper)

  2. Molecular biomarkers in idiopathic pulmonary fibrosis

    Science.gov (United States)

    Ley, Brett; Brown, Kevin K.

    2014-01-01

    Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF. PMID:25260757

  3. Curated compendium of human transcriptional biomarker data.

    Science.gov (United States)

    Golightly, Nathan P; Bell, Avery; Bischoff, Anna I; Hollingsworth, Parker D; Piccolo, Stephen R

    2018-04-17

    One important use of genome-wide transcriptional profiles is to identify relationships between transcription levels and patient outcomes. These translational insights can guide the development of biomarkers for clinical application. Data from thousands of translational-biomarker studies have been deposited in public repositories, enabling reuse. However, data-reuse efforts require considerable time and expertise because transcriptional data are generated using heterogeneous profiling technologies, preprocessed using diverse normalization procedures, and annotated in non-standard ways. To address this problem, we curated 45 publicly available, translational-biomarker datasets from a variety of human diseases. To increase the data's utility, we reprocessed the raw expression data using a uniform computational pipeline, addressed quality-control problems, mapped the clinical annotations to a controlled vocabulary, and prepared consistently structured, analysis-ready data files. These data, along with scripts we used to prepare the data, are available in a public repository. We believe these data will be particularly useful to researchers seeking to perform benchmarking studies-for example, to compare and optimize machine-learning algorithms' ability to predict biomedical outcomes.

  4. On Various Negative Translations

    Directory of Open Access Journals (Sweden)

    Gilda Ferreira

    2011-01-01

    Full Text Available Several proof translations of classical mathematics into intuitionistic mathematics have been proposed in the literature over the past century. These are normally referred to as negative translations or double-negation translations. Among those, the most commonly cited are translations due to Kolmogorov, Godel, Gentzen, Kuroda and Krivine (in chronological order. In this paper we propose a framework for explaining how these different translations are related to each other. More precisely, we define a notion of a (modular simplification starting from Kolmogorov translation, which leads to a partial order between different negative translations. In this derived ordering, Kuroda and Krivine are minimal elements. Two new minimal translations are introduced, with Godel and Gentzen translations sitting in between Kolmogorov and one of these new translations.

  5. Gender issues in translation

    OpenAIRE

    ERGASHEVA G.I.

    2015-01-01

    The following research is done regarding gender in translation dealing specifically with the issue of the translators’ gender identity and its effect on their translations, as well as on how gender itself is translated and produced. We will try to clarify what gender is, how gender manifests itself in the system of language, and what problems translators encounter when translating or producing gender-related materials

  6. Cultural Context and Translation

    Institute of Scientific and Technical Information of China (English)

    张敏

    2009-01-01

    cultural context plays an important role in translation. Because translation is a cross-culture activity, the culture context that influ-ences translating is consisted of both the culture contexts of source language and target language. This article firstly analyzes the concept of context and cultural context, then according to the procedure of translating classifies cultural context into two stages and talks about how they respectively influence translating.

  7. Biomarkers in DILI: one more step forward

    Directory of Open Access Journals (Sweden)

    Mercedes Robles-Díaz

    2016-08-01

    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.

  8. Translation-coupling systems

    Science.gov (United States)

    Pfleger, Brian; Mendez-Perez, Daniel

    2013-11-05

    Disclosed are systems and methods for coupling translation of a target gene to a detectable response gene. A version of the invention includes a translation-coupling cassette. The translation-coupling cassette includes a target gene, a response gene, a response-gene translation control element, and a secondary structure-forming sequence that reversibly forms a secondary structure masking the response-gene translation control element. Masking of the response-gene translation control element inhibits translation of the response gene. Full translation of the target gene results in unfolding of the secondary structure and consequent translation of the response gene. Translation of the target gene is determined by detecting presence of the response-gene protein product. The invention further includes RNA transcripts of the translation-coupling cassettes, vectors comprising the translation-coupling cassettes, hosts comprising the translation-coupling cassettes, methods of using the translation-coupling cassettes, and gene products produced with the translation-coupling cassettes.

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

    Science.gov (United States)

    Saito, Yoshiro; Nakamura, Ryosuke; Maekawa, Keiko

    2014-01-01

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

  10. Writing Through: Practising Translation

    Directory of Open Access Journals (Sweden)

    Joel Scott

    2010-05-01

    Full Text Available This essay exists as a segment in a line of study and writing practice that moves between a critical theory analysis of translation studies conceptions of language, and the practical questions of what those ideas might mean for contemporary translation and writing practice. Although the underlying preoccupation of this essay, and my more general line of inquiry, is translation studies and practice, in many ways translation is merely a way into a discussion on language. For this essay, translation is the threshold of language. But the two trails of the discussion never manage to elude each other, and these concatenations have informed two experimental translation methods, referred to here as Live Translations and Series Translations. Following the essay are a number of poems in translation, all of which come from Blanco Nuclear by the contemporary Spanish poet, Esteban Pujals Gesalí. The first group, the Live Translations consist of transcriptions I made from audio recordings read in a public setting, in which the texts were translated in situ, either off the page of original Spanish-language poems, or through a process very much like that carried out by simultaneous translators, for which readings of the poems were played back to me through headphones at varying speeds to be translated before the audience. The translations collected are imperfect renderings, attesting to a moment in language practice rather than language objects. The second method involves an iterative translation process, by which three versions of any one poem are rendered, with varying levels of fluency, fidelity and servility. All three translations are presented one after the other as a series, with no version asserting itself as the primary translation. These examples, as well as the translation methods themselves, are intended as preliminary experiments within an endlessly divergent continuum of potential methods and translations, and not as a complete representation of

  11. Imaging biomarkers as surrogate endpoints for drug development

    International Nuclear Information System (INIS)

    Richter, Wolf S.

    2006-01-01

    The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Proudfoot Alastair G

    2011-12-01

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

  13. Bioinformatics in translational drug discovery.

    Science.gov (United States)

    Wooller, Sarah K; Benstead-Hume, Graeme; Chen, Xiangrong; Ali, Yusuf; Pearl, Frances M G

    2017-08-31

    Bioinformatics approaches are becoming ever more essential in translational drug discovery both in academia and within the pharmaceutical industry. Computational exploitation of the increasing volumes of data generated during all phases of drug discovery is enabling key challenges of the process to be addressed. Here, we highlight some of the areas in which bioinformatics resources and methods are being developed to support the drug discovery pipeline. These include the creation of large data warehouses, bioinformatics algorithms to analyse 'big data' that identify novel drug targets and/or biomarkers, programs to assess the tractability of targets, and prediction of repositioning opportunities that use licensed drugs to treat additional indications. © 2017 The Author(s).

  14. Effective knowledge management in translational medicine.

    Science.gov (United States)

    Szalma, Sándor; Koka, Venkata; Khasanova, Tatiana; Perakslis, Eric D

    2010-07-19

    The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA) in the US and the Seventh Framework Programme (FP7) of EU with emphasis on translating research for human health. The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern. The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface. The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.

  15. Effective knowledge management in translational medicine

    Directory of Open Access Journals (Sweden)

    Khasanova Tatiana

    2010-07-01

    Full Text Available Abstract Background The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA in the US and the Seventh Framework Programme (FP7 of EU with emphasis on translating research for human health. Methods The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern. Results The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface. Conclusions The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.

  16. Why Translation Is Difficult

    DEFF Research Database (Denmark)

    Carl, Michael; Schaeffer, Moritz Jonas

    2017-01-01

    The paper develops a definition of translation literality that is based on the syntactic and semantic similarity of the source and the target texts. We provide theoretical and empirical evidence that absolute literal translations are easy to produce. Based on a multilingual corpus of alternative...... translations we investigate the effects of cross-lingual syntactic and semantic distance on translation production times and find that non-literality makes from-scratch translation and post-editing difficult. We show that statistical machine translation systems encounter even more difficulties with non-literality....

  17. Circulating Extracellular Vesicles Contain miRNAs and are Released as Early Biomarkers for Cardiac Injury

    NARCIS (Netherlands)

    Deddens, Janine C; Vrijsen, Krijn R; Colijn, Johanna M; Oerlemans, Marish; Metz, Corina H G; van der Vlist, Els J; Nolte-'t Hoen, Esther N M; den Ouden, Krista; Jansen of Lorkeers, SJ; van der Spoel, TIG; Koudstaal, Stefan; Arkesteijn, Ger J; Wauben, Marca H M; van Laake, Linda W; Doevendans, Pieter A; Chamuleau, Steven A J; Sluijter, Joost P G

    2016-01-01

    Plasma-circulating microRNAs have been implicated as novel early biomarkers for myocardial infarction (MI) due to their high specificity for cardiac injury. For swift clinical translation of this potential biomarker, it is important to understand their temporal and spatial characteristics upon MI.

  18. Cardiac biomarkers in Neonatology

    OpenAIRE

    Vijlbrief, D.C.

    2015-01-01

    In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

  19. Determinants of translation ambiguity

    Science.gov (United States)

    Degani, Tamar; Prior, Anat; Eddington, Chelsea M.; Arêas da Luz Fontes, Ana B.; Tokowicz, Natasha

    2016-01-01

    Ambiguity in translation is highly prevalent, and has consequences for second-language learning and for bilingual lexical processing. To better understand this phenomenon, the current study compared the determinants of translation ambiguity across four sets of translation norms from English to Spanish, Dutch, German and Hebrew. The number of translations an English word received was correlated across these different languages, and was also correlated with the number of senses the word has in English, demonstrating that translation ambiguity is partially determined by within-language semantic ambiguity. For semantically-ambiguous English words, the probability of the different translations in Spanish and Hebrew was predicted by the meaning-dominance structure in English, beyond the influence of other lexical and semantic factors, for bilinguals translating from their L1, and translating from their L2. These findings are consistent with models postulating direct access to meaning from L2 words for moderately-proficient bilinguals. PMID:27882188

  20. Translation in ESL Classes

    Directory of Open Access Journals (Sweden)

    Nagy Imola Katalin

    2015-12-01

    Full Text Available The problem of translation in foreign language classes cannot be dealt with unless we attempt to make an overview of what translation meant for language teaching in different periods of language pedagogy. From the translation-oriented grammar-translation method through the complete ban on translation and mother tongue during the times of the audio-lingual approaches, we have come today to reconsider the role and status of translation in ESL classes. This article attempts to advocate for translation as a useful ESL class activity, which can completely fulfil the requirements of communicativeness. We also attempt to identify some activities and games, which rely on translation in some books published in the 1990s and the 2000s.

  1. Translation and Quality Management

    DEFF Research Database (Denmark)

    Petersen, Margrethe

    1996-01-01

    theory which would seem likely to be of interest in this connection and section 2. gives a linguist's introduction to the part of the area of quality management which I consider relevant for present purposes. Section 3. is devoted to the case study of a small translation firm which has been certified......The aim of this article is to consider the issue of quality in translation. Specifically, the question under consideration is whether quality assurance in relation to translation is feasible and, if so, what some of the implications for translation theory, translation practice and the teaching...... of translation would be. To provide a backdrop against which the issue may be discussed, I present an overview of the two areas which seem most likely to hold potential answers, viz., that of translation theory and that of quality management. Section 1. gives a brief outline of some contributions to translation...

  2. Memetics and Translation Studies

    OpenAIRE

    Andrew, Chesterman

    2000-01-01

    Translation Studies is a branch of memetics. This is a claim, a hypothesis. More specifically, it is an interpretive hypothesis: I claim that Translation Studies can be thus interpreted, and that this is a useful thing to do because it offers a new and beneficial way of understanding translation.

  3. Sound Effects in Translation

    DEFF Research Database (Denmark)

    Mees, Inger M.; Dragsted, Barbara; Gorm Hansen, Inge

    2015-01-01

    ), Translog was employed to measure task times. The quality of the products was assessed by three experienced translators, and the number and types of misrecognitions were identified by a phonetician. Results indicate that SR translation provides a potentially useful supplement to written translation...

  4. Cardiovascular biomarkers and sex: the case for women.

    Science.gov (United States)

    Daniels, Lori B; Maisel, Alan S

    2015-10-01

    Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

  5. A tuberculosis biomarker database: the key to novel TB diagnostics

    Directory of Open Access Journals (Sweden)

    Seda Yerlikaya

    2017-03-01

    Full Text Available New diagnostic innovations for tuberculosis (TB, including point-of-care solutions, are critical to reach the goals of the End TB Strategy. However, despite decades of research, numerous reports on new biomarker candidates, and significant investment, no well-performing, simple and rapid TB diagnostic test is yet available on the market, and the search for accurate, non-DNA biomarkers remains a priority. To help overcome this ‘biomarker pipeline problem’, FIND and partners are working on the development of a well-curated and user-friendly TB biomarker database. The web-based database will enable the dynamic tracking of evidence surrounding biomarker candidates in relation to target product profiles (TPPs for needed TB diagnostics. It will be able to accommodate raw datasets and facilitate the verification of promising biomarker candidates and the identification of novel biomarker combinations. As such, the database will simplify data and knowledge sharing, empower collaboration, help in the coordination of efforts and allocation of resources, streamline the verification and validation of biomarker candidates, and ultimately lead to an accelerated translation into clinically useful tools.

  6. The Temple Translator's Workstation Project

    National Research Council Canada - National Science Library

    Vanni, Michelle; Zajac, Remi

    1996-01-01

    .... The Temple Translator's Workstation is incorporated into a Tipster document management architecture and it allows both translator/analysts and monolingual analysts to use the machine- translation...

  7. Sound Effects in Translation

    DEFF Research Database (Denmark)

    Mees, Inger M.; Dragsted, Barbara; Gorm Hansen, Inge

    2013-01-01

    On the basis of a pilot study using speech recognition (SR) software, this paper attempts to illustrate the benefits of adopting an interdisciplinary approach in translator training. It shows how the collaboration between phoneticians, translators and interpreters can (1) advance research, (2) have......), Translog was employed to measure task times. The quality of the products was assessed by three experienced translators, and the number and types of misrecognitions were identified by a phonetician. Results indicate that SR translation provides a potentially useful supplement to written translation...

  8. Lost in translation

    DEFF Research Database (Denmark)

    Hedegaard, Steffen; Simonsen, Jakob Grue

    2011-01-01

    of translated texts. Our results suggest (i) that frame-based classifiers are usable for author attribution of both translated and untranslated texts; (ii) that framebased classifiers generally perform worse than the baseline classifiers for untranslated texts, but (iii) perform as well as, or superior...... to the baseline classifiers on translated texts; (iv) that—contrary to current belief—naïve classifiers based on lexical markers may perform tolerably on translated texts if the combination of author and translator is present in the training set of a classifier....

  9. Speaking your Translation

    DEFF Research Database (Denmark)

    Dragsted, Barbara; Mees, Inger M.; Gorm Hansen, Inge

    2011-01-01

    In this article we discuss the translation processes and products of 14 MA students who produced translations from Danish (L1) into English (L2) under different working conditions: (1) written translation, (2) sight translation, and (3) sight translation with a speech recognition (SR) tool. Audio......, since students were dictating in their L2, we looked into the number and types of error that occurred when using the SR software. Items that were misrecognised by the program could be divided into three categories: homophones, hesitations, and incorrectly pronounced words. Well over fifty per cent...

  10. Lost in translation?

    DEFF Research Database (Denmark)

    Granas, Anne Gerd; Nørgaard, Lotte Stig; Sporrong, Sofia Kälvemark

    2014-01-01

    OBJECTIVE: The "Beliefs about Medicines Questionnaire" (BMQ) assess balance of necessity and concern of medicines. The BMQ has been translated from English to many languages. However, the original meaning of statements, such as "My medicine is a mystery to me", may be lost in translation. The aim...... of this study is to compare three Scandinavian translations of the BMQ. (1) How reliable are the translations? (2) Are they still valid after translation? METHODS: Translated Norwegian, Swedish and Danish versions of the BMQ were scrutinized by three native Scandinavian researchers. Linguistic differences...... and ambiguities in the 5-point Likert scale and the BMQ statements were compared. RESULTS: In the Scandinavian translations, the Likert scale expanded beyond the original version at one endpoint (Swedish) or both endpoints (Danish). In the BMQ statements, discrepancies ranged from smaller inaccuracies toward...

  11. What is a translator?

    Directory of Open Access Journals (Sweden)

    Martha Pulido

    2016-08-01

    Full Text Available I copied the title from Foucault’s text, "Qu'est-ce qu'un auteur" in Dits et écrits [1969], Paris, Gallimard, 1994, that I read in French, then in English in Donald F. Bouchard’s and Sherry Simon’s translation, and finally in Spanish in Yturbe Corina’s translation, and applied for the translator some of the analysis that Foucault presents to define the author. Foucault suggests that if we cannot define an author, at least we can see where their function is reflected. My purpose in this paper is to present those surfaces where the function of the translator is reflected or where it can be revealed, and to analyse the categories that could lead us to the elaboration of a suitable definition of a Translator. I dare already give a compound noun for the translator: Translator-Function.

  12. What is a translator?

    Directory of Open Access Journals (Sweden)

    Martha Martha Pulido

    2016-05-01

    Full Text Available I copied the title from Foucault’s text, "Qu'est-ce qu'un auteur" in Dits et écrits [1969], Paris, Gallimard, 1994, that I read in French, then in English in Donald F. Bouchard’s and Sherry Simon’s translation, and finally in Spanish in Yturbe Corina’s translation, and applied for the translator some of the analysis that Foucault presents to define the author. Foucault suggests that if we cannot define an author, at least we can see where their function is reflected. My purpose in this paper is to present those surfaces where the function of the translator is reflected or where it can be revealed, and to analyse the categories that could lead us to the elaboration of a suitable definition of a Translator. I dare already give a compound noun for the translator: Translator-Function.

  13. Urine biomarkers in the early stages of diseases: current status and perspective.

    Science.gov (United States)

    Jing, Jian; Gao, Youhe

    2018-02-01

    As a noninvasive and easily available biological fluid, the urine is becoming an important source for disease biomarker study. Change is essential for the usefulness of a biomarker. Without homeostasis mechanisms, urine can accommodate more changes, especially in the early stages of diseases. In this review, we summarize current status and discuss perspectives on the discovery of urine biomarkers in the early stages of diseases. We emphasize the advantages of urine biomarkers compared to plasma biomarkers for the diagnosis of diseases at early stages, propose a urine biomarker research roadmap, and highlight a novel membrane storage technique that enables large-scale urine sample collection and storage efficiently and economically. It is anticipated that urine biomarker studies will greatly promote early diagnosis, prevention, treatment, and prognosis of a variety of diseases, and provide strong support for translational and precision medicine.

  14. Biomarkers in Autism

    Directory of Open Access Journals (Sweden)

    Robert eHendren

    2014-08-01

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

  15. The use of biomarkers in occupational health research, practice, and policy.

    Science.gov (United States)

    Schulte, P A; Hauser, J E

    2012-08-13

    Biomarkers are potentially useful tools for occupational health and safety research, practice, and policy. However, the full realization of this potential has not been achieved. In this paper, the progress made in these three usage areas is reviewed to identify what efforts can be taken to realize the full promise of biomarkers. Biomarker uses are described by a diverse taxonomy that builds on the categories of exposure, effect and susceptibility, and the continuum between exposure and disease prognosis. The most significant uses of biomarkers in occupational health have been in biological monitoring of workers. Other important uses have been in enhancing research and assessing mechanisms of action of occupational toxicants at low exposures. Seven critical areas will influence the extent to which the potential of biomarkers in occupational health and safety is realized. These include: (1) adequate investment in validation; (2) obtaining international agreement on exposure guidelines; (3) exploring the utility of biomarkers in regulation; (4) applying biomarkers to critical occupational safety and health questions; (5) developing the exposome; (6) utilizing biomarkers to address emerging occupational health issues; and (7) continuing to address the ethical and social justice issues related to biomarkers. Overall, if biomarkers are to make a major contribution to occupational health and safety then a more holistic approach to bringing them from the laboratory to practice will be needed. Published by Elsevier Ireland Ltd.

  16. Discourse Analysis in Translator Training

    OpenAIRE

    Gülfidan Ayvaz

    2015-01-01

    Translator training enables students to gain experience in both linguistic parameters and translation practice. Discourse Analysis is one of the strategies that lead to a better translation process and quality in translation. In that regard, this study aims to present DA as a translation strategy for translation practice and a useful tool for translator training. The relationship between DA and Translator Training is not widely studied. Therefore this study aims to define DA and how it can be...

  17. Biomarkers for sepsis: past, present and future

    Directory of Open Access Journals (Sweden)

    Giuseppe Chesi

    2016-12-01

    Full Text Available Sepsis is a complication of severe infection associated with high mortality and open diagnostic issues. Treatment strategies are currently limited and essentially based on prompt recognition, aggressive supportive care and early antibiotic treatment. In the last years, extensive antibiotic use has led to selection, propagation and maintenance of drug-resistant microorganisms. In this context, several biomarkers have been proposed for early identification, etiological definition, risk stratification and improving antibiotic stewardship in septic patient care. Among these molecules, only a few have been translated into clinical practice. In this review, we provided an updated overview of established and developing biomarkers for sepsis, focusing our attention on their pathophysiological profile, advantages, limitations, and appropriate evidence-based use in the management of septic patients.

  18. Prognostic biomarkers in osteoarthritis

    Science.gov (United States)

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

    2013-01-01

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

  19. Struggling with Translations

    DEFF Research Database (Denmark)

    Obed Madsen, Søren

    This paper shows empirical how actors have difficulties with translating strategy texts. The paper uses four cases as different examples of what happens, and what might be difficult, when actors translate organizational texts. In order to explore this, it draws on a translation training method from...... translation theory. The study shows that for those who have produced the text, it is difficult to translate a strategy where they have to change the words so others who don’t understand the language in the text can understand it. It also shows that for those who haven’t been a part of the production, it very...... challenge the notion that actors understand all texts and that managers per se can translate a text....

  20. Translational ecology for hydrogeology.

    Science.gov (United States)

    Schlesinger, William H

    2013-01-01

    Translational ecology--a special discipline aimed to improve the accessibility of science to policy makers--will help hydrogeologists contribute to the solution of pressing environmental problems. Patterned after translational medicine, translational ecology is a partnership to ensure that the right science gets done in a timely fashion, so that it can be communicated to those who need it. © 2013, National Ground Water Association.

  1. Translation and Intertextuality

    Directory of Open Access Journals (Sweden)

    Mohammad Rahimi

    2015-09-01

    Full Text Available This study is intends to describe and Presents a new theory of translation based on the "Intertextuality" unlike the Translation theories that presented to date, what all are based on the principle of "Equivalence". Our theory is based on the examples of Arabic poetry translated into Persian poetry. The major findings of this study show that the Intertextuality can serve as a link between the original text and the target. it can also interact with other texts is the translation result in the target language, Whtich is the book of poetic eloquence is addressed and was mentioned Literary robbery.

  2. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    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.

  3. amphibian_biomarker_data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Amphibian metabolite data used in Snyder, M.N., Henderson, W.M., Glinski, D.G., Purucker, S. T., 2017. Biomarker analysis of american toad (Anaxyrus americanus) and...

  4. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  5. Lost in Translation?

    NARCIS (Netherlands)

    Jonkers, Peter

    2017-01-01

    Translating sacred scriptures is not only a praxis that is crucial for the fruitful, i.e. non-distorted and unbiased dialogue between different religious traditions, but also raises some fundamental theoretical questions when it comes to translating the sacred texts of the religious other or

  6. Translating VDM to Alloy

    DEFF Research Database (Denmark)

    Lausdahl, Kenneth

    2013-01-01

    specifications. However, to take advantage of the automated analysis of Alloy, the model-oriented VDM specifications must be translated into a constraint-based Alloy specifications. We describe how a sub- set of VDM can be translated into Alloy and how assertions can be expressed in VDM and checked by the Alloy...

  7. Students' Differentiated Translation Processes

    Science.gov (United States)

    Bossé, Michael J.; Adu-Gyamfi, Kwaku; Chandler, Kayla

    2014-01-01

    Understanding how students translate between mathematical representations is of both practical and theoretical importance. This study examined students' processes in their generation of symbolic and graphic representations of given polynomial functions. The purpose was to investigate how students perform these translations. The result of the study…

  8. Creativity, Culture and Translation

    Science.gov (United States)

    Babaee, Siamak; Wan Yahya, Wan Roselezam; Babaee, Ruzbeh

    2014-01-01

    Some scholars (Bassnett-McGuire, Catford, Brislin) suggest that a good piece of translation should be a strict reflection of the style of the original text while some others (Gui, Newmark, Wilss) consider the original text untranslatable unless it is reproduced. Opposing views by different critics suggest that translation is still a challenging…

  9. Translation as (Global) Writing

    Science.gov (United States)

    Horner, Bruce; Tetreault, Laura

    2016-01-01

    This article explores translation as a useful point of departure and framework for taking a translingual approach to writing engaging globalization. Globalization and the knowledge economy are putting renewed emphasis on translation as a key site of contest between a dominant language ideology of monolingualism aligned with fast capitalist…

  10. Measuring Translation Literality

    DEFF Research Database (Denmark)

    Carl, Michael; Schaeffer, Moritz

    2017-01-01

    Tirkkonen-Condit (2005: 407–408) argues that “It looks as if literal translation is [the result of] a default rendering procedure”. As a corollary, more literal translations should be easier to process, and less literal ones should be associated with more cognitive effort. In order to assess this...

  11. Text Coherence in Translation

    Science.gov (United States)

    Zheng, Yanping

    2009-01-01

    In the thesis a coherent text is defined as a continuity of senses of the outcome of combining concepts and relations into a network composed of knowledge space centered around main topics. And the author maintains that in order to obtain the coherence of a target language text from a source text during the process of translation, a translator can…

  12. TRANSLATING SERVICE TECHNICAL PROSE

    African Journals Online (AJOL)

    language. The Application of Technical Service. Prose. To form a good idea of the appl ication .... cost lives. In this particular domain, translators must have a sound technical ... These semantic ... another language and often, in doing so, changing its meaning. The words ..... He will hand out tasks to each translator and after.

  13. Stimulating translational research

    DEFF Research Database (Denmark)

    Bentires-Alj, Mohamed; Rajan, Abinaya; van Harten, Wim

    2015-01-01

    Translational research leaves no-one indifferent and everyone expects a particular benefit. We as EU-LIFE (www.eu-life.eu), an alliance of 13 research institutes in European life sciences, would like to share our experience in an attempt to identify measures to promote translational research with...... without undermining basic exploratory research and academic freedom....

  14. Translation, Quality and Growth

    DEFF Research Database (Denmark)

    Petersen, Margrethe

    The paper investigates the feasibility and some of the possible consequences of applying quality management to translation. It first gives an introduction to two different schools of translation and to (total) quality management. It then examines whether quality management may, in theory...

  15. Translation, Interpreting and Lexicography

    DEFF Research Database (Denmark)

    Dam, Helle Vrønning; Tarp, Sven

    2018-01-01

    in the sense that their practice fields are typically ‘about something else’. Translators may, for example, be called upon to translate medical texts, and interpreters may be assigned to work on medical speeches. Similarly, practical lexicography may produce medical dictionaries. In this perspective, the three...

  16. Translation between cultures

    Directory of Open Access Journals (Sweden)

    Henrique de Oliveira Lee

    2016-05-01

    Full Text Available This article will question the pertinence of understanding interculturality in terms of translation between cultures. I shall study this hypothesis in two ways : 1 / the cosmopolitan horizon, which the idea of translation may implicate ; 2 / the critique of the premises of unique origin and homogeneity of cultures which this hypothesis makes possible.

  17. Idioms and Back Translation

    Science.gov (United States)

    Griffin, Frank

    2004-01-01

    The challenges of intercultural communication are an integral part of many undergraduate business communication courses. Marketing gaffes clearly illustrate the pitfalls of translation and underscore the importance of a knowledge of the culture with which one is attempting to communicate. A good way to approach the topic of translation pitfalls in…

  18. Translational science: past, present, and future.

    Science.gov (United States)

    Curry, Stephen H

    2008-02-01

    The concept of translational science is at least 15 years old. However, in its most recent incarnation, it represents the identification of a funding category designed to encourage academic participation in a critical stage of the drug discovery and product development process. It is hoped that this will make the process both shorter and more efficient. In this review, the author first considers the historical development of the pharmaceutical R&D process. The place of translational science in the process, the scientific techniques involved, and aspects of the business environment necessary for its success are then considered. Translational science does not displace preclinical development. Both concepts are relevant to the paramount importance of successfully and expeditiously bridging the gap between preclinical science and clinical testing, "from bench to bedside." Translational science is particularly likely to stimulate biomarker research in the universities and related business community and will probably give a modest boost to early clinical testing and commercialization of discoveries within the academic setting. Whether there will be a consequent improvement in the quality and efficiency of the overall process remains to be seen.

  19. Translation Ambiguity but Not Word Class Predicts Translation Performance

    Science.gov (United States)

    Prior, Anat; Kroll, Judith F.; Macwhinney, Brian

    2013-01-01

    We investigated the influence of word class and translation ambiguity on cross-linguistic representation and processing. Bilingual speakers of English and Spanish performed translation production and translation recognition tasks on nouns and verbs in both languages. Words either had a single translation or more than one translation. Translation…

  20. Examining English-German Translation Ambiguity Using Primed Translation Recognition

    Science.gov (United States)

    Eddington, Chelsea M.; Tokowicz, Natasha

    2013-01-01

    Many words have more than one translation across languages. Such "translation-ambiguous" words are translated more slowly and less accurately than their unambiguous counterparts. We examine the extent to which word context and translation dominance influence the processing of translation-ambiguous words. We further examine how these factors…

  1. Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience

    Science.gov (United States)

    2015-10-01

    15. SUBJECT TERMS Spinal cord injury, pressure ulcer prevention, biomarkers, personalized healthcare 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...pressure ulcer prevention, biomarkers, personalized healthcare 3. Accomplishments Major Project Goals Task 1: Subject Recruitment and Data...months (Co-Investigator) Clinically translatable nanotechnology : hemostasis and neuroprotection New studies 09/30/14 -09/30/15 Started 01/01/15

  2. Personalized translational epilepsy research - Novel approaches and future perspectives: Part II: Experimental and translational approaches.

    Science.gov (United States)

    Bauer, Sebastian; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Rosenow, Felix

    2017-11-01

    Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1]. Copyright © 2017

  3. Theory of Test Translation Error

    Science.gov (United States)

    Solano-Flores, Guillermo; Backhoff, Eduardo; Contreras-Nino, Luis Angel

    2009-01-01

    In this article, we present a theory of test translation whose intent is to provide the conceptual foundation for effective, systematic work in the process of test translation and test translation review. According to the theory, translation error is multidimensional; it is not simply the consequence of defective translation but an inevitable fact…

  4. Translation, Cultural Translation and the Hegemonic English

    Directory of Open Access Journals (Sweden)

    Roman Horak

    2015-01-01

    Full Text Available This brief chapter problematizes the hegemonic position of the English language in Cultural Studies, which, in the author's view, can be understood as a moment that stands against a true internationalisation of the project. Following an argu-ment referring to the necessary 'translation' process (here seen as 're-articulation', 'transcoding' or 'transculturation' Stuart Hall has put forward almost two decades ago, the essay, firstly, turns to the notion of 'linguistic translations', and deals, secondly, with what has been coined 'cultural translation'. Discussing approaches developed by Walter Benjamin, Umberto Eco and Homi Bhabha, the complex relationship between the two terms is being investigated. Finally, in a modest attempt to throw some light on this hegemonic structure, central aspects of the output of three important journals (European Journal of Cultural Studies, International Journal of Cultural Studies, Cultural Studies, i. e. an analysis of the linguistic and institutional backgrounds of the authors of the ten most-read and most-cited essays, are presented. Based on these findings I argue that it is not simply the addition of the discursive field (language to the academic space (institution that defines the mecha-nism of exclusion and inclusion. Rather, it is the articulation of both moments, i.e. that of language and that of the institution, which - in various contexts (but in their own very definite ways - can help to develop that structure which at present is still hindering a further, more profound internationalisation of the project that is Cultural Studies.

  5. Translation of feminine: Szymborska

    Directory of Open Access Journals (Sweden)

    Olga Donata Guerizoli Kempinska

    2014-07-01

    Full Text Available http://dx.doi.org/10.5007/2175-7968.2014v1n33p35 The paper discusses the problems present in the process of the translation of the feminine, related to the discursive articulations of the gender and to the socio-historical conditions of its construction. The differences between languages make this articulation hard to transpose and such is the case in some of Wisława Szymborska’s poems. An attentive reading of her work and of its translations in different languages reveals that the transposition of its specifically feminine humor is also a challenge for the translator

  6. Biomarkers of sepsis

    Science.gov (United States)

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  7. Mass spectrometry for biomarker development

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  8. Perceived radial translation during centrifugation

    NARCIS (Netherlands)

    Bos, J.E.; Correia Grácio, B.J.

    2015-01-01

    BACKGROUND: Linear acceleration generally gives rise to translation perception. Centripetal acceleration during centrifugation, however, has never been reported giving rise to a radial, inward translation perception. OBJECTIVE: To study whether centrifugation can induce a radial translation

  9. What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema.

    Science.gov (United States)

    Ptolemy, Adam S; Rifai, Nader

    2010-01-01

    A continual trend of annual growth can be seen within research devoted to the discovery and validation of disease biomarkers within both the natural and clinical sciences. This expansion of intellectual endeavours was quantified through database searches of (a) research grant awards provided by the various branches of the National Institutes of Health (NIH) and (b) academic publications. A search of awards presented between 1986 and 2009 revealed a total of 28,856 grants awarded by the NIH containing the term "biomarker". The total funds for these awards in 2008 and 2009 alone were over $2.5 billion. During the same respective time frames, searches of "biomarker" and either "discovery", "genomics", "proteomics" or "metabolomics" yielded a total of 4,928 NIH grants whose combined funding exceeded $1.2 billion. The derived trend in NIH awards paralleled the annual expansion in "biomarker" literature. A PubMed search for the term, between 1990 and 2009, revealed a total of 441,510 published articles, with 38,457 published in 2008. These enormous investments and academic outputs however have not translated into the expected integration of new biomarkers for patient care. For example no proteomics derived biomarkers are currently being utilized in routine clinical management. This translational chasm necessitates a review of the previously proposed biomarker definitions and evaluation schema. A subsequent discussion of both the analytical and pre-analytical considerations for such research is also presented within. This required knowledge should aid scientists in their pursuit and validation of new biological markers of disease.

  10. Biomarkers of drug-induced vascular injury

    International Nuclear Information System (INIS)

    Brott, D.; Gould, S.; Jones, H.; Schofield, J.; Prior, H.; Valentin, J.P; Bjurstrom, S.; Kenne, K.; Schuppe-Koistinen, I.; Katein, A.; Foster-Brown, L.; Betton, G.; Richardson, R.; Evans, G.; Louden, C.

    2005-01-01

    In pre-clinical safety studies, drug-induced vascular injury is an issue of concern because there are no obvious diagnostic markers for pre-clinical or clinical monitoring and there is an intellectual gap in our understanding of the pathogenesis of this lesion. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary targets, smooth muscle and endothelial cells are unknown. However, evaluation of novel markers for potential clinical monitoring with a mechanistic underpinning would add value in risk assessment and management. This mini review focuses on the progress to identify diagnostic markers of drug-induced vascular injury. Von Willebrand factor (vWF), released upon perturbation of endothelial cells, is transiently increased in plasma prior to morphological evidence of damage in dogs or rats treated with vascular toxicants. Therefore, vWF might be a predictive biomarker of vascular injury. However, vWF is not an appropriate biomarker of lesion progression or severity since levels return to baseline values when there is morphological evidence of injury. A potential mechanistically linked biomarker of vascular injury is caveolin-1. Expression of this protein, localized primarily to smooth muscle and endothelial cells, decreases with the onset of vascular damage. Since vascular injury involves multiple mediators and cell types, evaluation of a panel rather than a single biomarker may be more useful in monitoring early and severe progressive vascular injury

  11. Russian translations for Cochrane.

    Science.gov (United States)

    Yudina, E V; Ziganshina, L E

    2015-01-01

    Cochrane collaboration has made a huge contribution to the development of evidence-based medicine; Cochrane work is the international gold standard of independent, credible and reliable high-quality information in medicine. Over the past 20 years the Cochrane Collaboration helped transforming decision-making in health and reforming it significantly, saving lives and contributing to longevity [1]. Until recently, Cochrane evidence were available only in English, which represents a significant barrier to their wider use in non-English speaking countries. To provide access to evidence, obtained from Cochrane Reviews, for health professionals and general public (from non-English-speaking countries), bypassing language barriers, Cochrane collaboration in 2014 initiated an international project of translating Plain language summaries of Cochrane Reviews into other languages [2, 3]. Russian translations of Plain language summaries were started in May 2014 by the team from Kazan Federal University (Department of Basic and Clinical Pharmacology; 2014-2015 as an Affiliated Centre in Tatarstan of the Nordic Cochrane Centre, since August 2015 as Cochrane Russia, a Russian branch of Cochrane Nordic, Head - Liliya Eugenevna Ziganshina) on a voluntary basis. To assess the quality of Russian translations of Cochrane Plain Language Summaries (PLS) and their potential impact on the Russian speaking community through user feedback with the overarching aim of furthering the translations project. We conducted the continuous online survey via Google Docs. We invited respondents through the electronic Russian language discussion forum on Essential Medicines (E-lek), links to survey on the Russian Cochrane.org website, invitations to Cochrane contributors registered in Archie from potential Russian-speaking countries. We set up the survey in Russian and English. The respondents were asked to respond to the questionnaire regarding the relevance and potential impact of the Cochrane Russian

  12. A phased translation function

    International Nuclear Information System (INIS)

    Read, R.J.; Schierbeek, A.J.

    1988-01-01

    A phased translation function, which takes advantage of prior phase information to determine the position of an oriented mulecular replacement model, is examined. The function is the coefficient of correlation between the electron density computed with the prior phases and the electron density of the translated model, evaluated in reciprocal space as a Fourier transform. The correlation coefficient used in this work is closely related to an overlap function devised by Colman, Fehlhammer and Bartels. Tests with two protein structures, one of which was solved with the help of the phased translation function, show that little phase information is required to resolve the translation problem, and that the function is relatively insensitive to misorientation of the model. (orig.)

  13. Translation and Creation

    Directory of Open Access Journals (Sweden)

    Paulo Bezerra

    2012-12-01

    Full Text Available The article begins with the differences betweenscientific and fictional translations, and focus on the second.The fictional translation works with meanings, opens itselfto the plurissignification in the purpose to create a similarity of the dissimilarity; in this process, the translator does nottranslate a language, but what a creative individuality makeswith a language. At last there is an approach to the knowledgeand skills necessaries to a translator of literature: theknowledge of the theories of the literature and of thetranslation, the capacity to preserve the national color ofthe original text and at the same time to respect the arrivallanguage, and the sensibility to his national languagevariations present in the daily and in the literary spheres.

  14. Translation of research outcome

    African Journals Online (AJOL)

    unhcc

    2017-01-03

    Jan 3, 2017 ... we must act”1 - Translation of research outcome for health policy, strategy and ... others iron-out existing gaps on Health Policy .... within the broader framework of global call and ... research: defining the terrain; identifying.

  15. Staging Ethnographic Translation

    DEFF Research Database (Denmark)

    Lundberg, Pia

    2009-01-01

    Objectifying the cultural diversity of visual fieldmethods - and the analysis of balancing the cultural known and unknown through anthropological analysis (aided by the analytical concept translation (Edwin Ardener 1989))...

  16. Translation for language purposes

    DEFF Research Database (Denmark)

    Schjoldager, Anne

    2003-01-01

    The paper describes the background, subjects, assumptions, procedure, and preliminary results of a small-scale experimental study of L2 translation (Danish into English) and picture verbalization in L2 (English)....

  17. Exploration of Disease Markers under Translational Medicine Model

    Directory of Open Access Journals (Sweden)

    Rajagopal Krishnamoorthy

    2015-06-01

    Full Text Available Disease markers are defined as the biomarkers with specific characteristics during the general physical, pathological or therapeutic process, the detection of which can inform the progression of present biological process of organisms. However, the exploration of disease markers is complicated and difficult, and only a few markers can be used in clinical practice and there is no significant difference in the mortality of cancers before and after biomarker exploration. Translational medicine focuses on breaking the blockage between basic medicine and clinical practice. In addition, it also establishes an effective association between researchers engaged on basic scientific discovery and clinical physicians well informed of patients' requirements, and gives particular attentions on how to translate the basic molecular biological research to the most effective and appropriate methods for the diagnosis, treatment and prevention of diseases, hoping to translate basic research into the new therapeutic methods in clinic. Therefore, this study mainly summarized the exploration of disease markers under translational medicine model so as to provide a basis for the translation of basic research results into clinical application.

  18. Urine Exosomes: An Emerging Trove of Biomarkers.

    Science.gov (United States)

    Street, J M; Koritzinsky, E H; Glispie, D M; Star, R A; Yuen, P S T

    Exosomes are released by most cells and can be isolated from all biofluids including urine. Exosomes are small vesicles formed as part of the endosomal pathway that contain cellular material surrounded by a lipid bilayer that can be traced to the plasma membrane. Exosomes are potentially a more targeted source of material for biomarker discovery than unfractionated urine, and provide diagnostic and pathophysiological information without an invasive tissue biopsy. Cytoplasmic contents including protein, mRNA, miRNA, and lipids have all been studied within the exosomal fraction. Many prospective urinary exosomal biomarkers have been successfully identified for a variety of kidney or genitourinary tract conditions; detection of systemic conditions may also be possible. Isolation and analysis of exosomes can be achieved by several approaches, although many require specialized equipment or involve lengthy protocols. The need for timely analysis in the clinical setting has driven considerable innovation with several promising options recently emerging. Consensus on exosome isolation, characterization, and normalization procedures would resolve critical clinical translational bottlenecks for existing candidate exosomal biomarkers and provide a template for additional discovery studies. 2017 Published by Elsevier Inc.

  19. Shotgun Proteomics and Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    W. Hayes McDonald

    2002-01-01

    Full Text Available Coupling large-scale sequencing projects with the amino acid sequence information that can be gleaned from tandem mass spectrometry (MS/MS has made it much easier to analyze complex mixtures of proteins. The limits of this “shotgun” approach, in which the protein mixture is proteolytically digested before separation, can be further expanded by separating the resulting mixture of peptides prior to MS/MS analysis. Both single dimensional high pressure liquid chromatography (LC and multidimensional LC (LC/LC can be directly interfaced with the mass spectrometer to allow for automated collection of tremendous quantities of data. While there is no single technique that addresses all proteomic challenges, the shotgun approaches, especially LC/LC-MS/MS-based techniques such as MudPIT (multidimensional protein identification technology, show advantages over gel-based techniques in speed, sensitivity, scope of analysis, and dynamic range. Advances in the ability to quantitate differences between samples and to detect for an array of post-translational modifications allow for the discovery of classes of protein biomarkers that were previously unassailable.

  20. Lost in Translation

    Science.gov (United States)

    Lass, Wiebke; Reusswig, Fritz

    2014-05-01

    Lost in Translation? Introducing Planetary Boundaries into Social Systems. Fritz Reusswig, Wiebke Lass Potsdam Institute for Climate Impact Research, Potsdam, Germany Identifying and quantifying planetary boundaries by interdisciplinary science efforts is a challenging task—and a risky one, as the 1972 Limits to Growth publication has shown. Even if we may be assured that scientific understanding of underlying processes of the Earth system has significantly improved since then, the challenge of translating these findings into the social systems of the planet remains crucial for any kind of action, and in many respects far more challenging. We would like to conceptualize what could also be termed a problem of coupling social and natural systems as a nested set of social translation processes, well aware of the limited applicability of the language-related translation metaphor. Societies must, first, perceive these boundaries, and they have to understand their relevance. This includes, among many other things, the organization of transdisciplinary scientific cooperation. They will then have to translate this understood perception into possible actions, i.e. strategies for different local bodies, actors, and institutional settings. This implies a lot of 'internal' translation processes, e.g. from the scientific subsystem to the mass media, the political and the economic subsystem. And it implies to develop subsystem-specific schemes of evaluation for these alternatives, e.g. convincing narratives, cost-benefit analyses, or ethical legitimacy considerations. And, finally, societies do have to translate chosen action alternatives into monitoring and evaluation schemes, e.g. for agricultural production or renewable energies. This process includes the continuation of observing and re-analyzing the planetary boundary concept itself, as a re-adjustment of these boundaries in the light of new scientific insights cannot be excluded. Taken all together, societies may well

  1. Biomarkers of the Dementia

    Directory of Open Access Journals (Sweden)

    Mikio Shoji

    2011-01-01

    Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

  2. Inflammatory biomarkers and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

    2017-01-01

    and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C-reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow-up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs......In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...

  3. [Biomarkers in emergency medicine and critical care patients: advances and pitfalls for news tools].

    Science.gov (United States)

    Claessens, Yann-Erick; Mallet-Coste, Thomas; Riqué, Thomas; Macchi, Marc-Alexis; Ray, Patrick; Chenevier-Gobeaux, Camille

    2014-01-01

    The use of biomarkers has changed approach of diagnosis and treatment procedures in emergency medicine, especially in the field of cardiovascular disorders. Effectiveness of new strategies that integrate biomarkers has precluded development and research in novel tools that may improve safety and efficiency at bedside. This mini-review presents current knowledge on utility of biomarkers in emergency medicine, including data that should be taken into account to avoid misleading utilization. Copyright © 2013. Published by Elsevier Masson SAS.

  4. Lost in translation?

    DEFF Research Database (Denmark)

    Zethsen, Karen Korning; Askehave, Inger

    2011-01-01

    This article deals with an aspect of patient information that differs somewhat from the traditional scope of this journal; namely the linguistic and translational aspects of Patient Information Leaflets (PILs). During the past decade much work has been dedicated to making the English PILs...... as informative and lay-friendly as possible. However, much of the good work is ruined when the PIL is translated. Why is this so and what can be done about it?...

  5. Machine Translation from Text

    Science.gov (United States)

    Habash, Nizar; Olive, Joseph; Christianson, Caitlin; McCary, John

    Machine translation (MT) from text, the topic of this chapter, is perhaps the heart of the GALE project. Beyond being a well defined application that stands on its own, MT from text is the link between the automatic speech recognition component and the distillation component. The focus of MT in GALE is on translating from Arabic or Chinese to English. The three languages represent a wide range of linguistic diversity and make the GALE MT task rather challenging and exciting.

  6. Jungmann's translation of Paradise Lost

    OpenAIRE

    Janů, Karel

    2014-01-01

    This thesis examines Josef Jungmann's translation of John Milton's Paradise Lost. Josef Jungmann was one of the leading figures of the Czech National Revival and translated Milton 's poem between the years 1800 and 1804. The thesis covers Jungmann's theoretical model of translation and presents Jungmann's motives for translation of Milton's epic poem. The paper also describes the aims Jungmann had with his translation and whether he has achieved them. The reception Jungmann's translation rece...

  7. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Science.gov (United States)

    Chauhan, Ranjit; Lahiri, Nivedita

    2016-01-01

    Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID:27398029

  8. Potential biomarkers for bipolar disorder: Where do we stand?

    Directory of Open Access Journals (Sweden)

    Rajesh Sagar

    2017-01-01

    Full Text Available Bipolar disorder (BD is a severe, recurrent mood disorder, associated with a significant morbidity and mortality, with high rates of suicides and medical comorbidities. There is a high risk of mood disorders among the first-degree relatives of patients with BD. In the current clinical practice, the diagnosis of BD is made by history taking, interview and behavioural observations, thereby lacking an objective, biological validation. This approach may result in underdiagnosis, misdiagnosis and eventually poorer outcomes. Due to the heterogeneity of BD, the possibility of developing a single, specific biomarker is still remote; however, there is a set of promising biomarkers which may serve as predictive, prognostic or treatment markers in the future. The review presents a critical appraisal and update on some of the most promising candidates for biomarkers, namely, neuroimaging markers, peripheral biomarkers and genetic markers, including a brief discussion on cognitive endophenotypes as indicative of genetic risk. The lessons learnt from other fields and specialties in medicine need to be applied to psychiatry to translate the knowledge from 'bench to bedside' by means of clinically useful biomarkers. Overall, the biomarkers may help in pushing the shift towards personalized medicine for psychiatric patients.

  9. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ranjit Chauhan

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC, one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

  10. An epigenetic biomarker of aging for lifespan and healthspan

    Science.gov (United States)

    Levine, Morgan E.; Lu, Ake T.; Quach, Austin; Chen, Brian H.; Assimes, Themistocles L.; Bandinelli, Stefania; Hou, Lifang; Baccarelli, Andrea A.; Stewart, James D.; Li, Yun; Whitsel, Eric A.; Wilson, James G; Reiner, Alex P; Aviv, Abraham; Lohman, Kurt; Liu, Yongmei; Ferrucci, Luigi

    2018-01-01

    Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging. PMID:29676998

  11. Translating Alcohol Research

    Science.gov (United States)

    Batman, Angela M.; Miles, Michael F.

    2015-01-01

    Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of streamlining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD. PMID:26259085

  12. The Effect of Translators' Emotional Intelligence on Their Translation Quality

    Science.gov (United States)

    Varzande, Mohsen; Jadidi, Esmaeil

    2015-01-01

    Translators differ from each other in many ways in terms of their knowledge, professional and psychological conditions that may directly influence their translation. The present study aimed at investigating the impact of translators' Emotional Intelligence on their translation quality. Following a "causal-comparative study," a sample of…

  13. The Impact of Translators' Academic Experience on Their Translation Quality

    Science.gov (United States)

    Varzande, Mohsen; Jadidi, Esmaeil

    2015-01-01

    Translators differ from each other in many ways in terms of their knowledge and professional conditions that may directly influence their translation. The present study aimed at investigating the impact of translators' academic experience on their translation quality. Following a "causal-comparative study", a sample of 100 male and…

  14. Translating Signs, Producing Subjects

    Directory of Open Access Journals (Sweden)

    Brett Neilson

    2009-08-01

    Full Text Available This paper moves between two streets: Liverpool Road in the Sydney suburb of Ashfield and Via Sarpi in the Italian city of Milan. What connects these streets is that both have become important sites for businesses in the Chinese diaspora. Moreover, both are streets on which locals have expressed desires for Chinese signs to be translated into the national lingua franca. The paper argues that the cultural politics inherent in this demand for translation cannot be fully understood in the context of national debates about diversity and integration. It is also necessary to consider the emergence of the official Chinese Putonghua as global language, which competes with English but also colonizes dialects and minority languages. In the case of these dual language signs, the space between languages can neither be reduced to a contact zone of minority and majority cultures nor celebrated as a ‘third space’ where the power relations implied by such differences are subverted. At stake is rather a space characterised by what Naoki Sakai calls the schema of co-figuration, which allows the representation of translation as the passage between two equivalents that resemble each other and thus makes possible their determination as conceptually different and comparable. Drawing on arguments about translation and citizenship, the paper critically interrogates the ethos of interchangeability implied by this regime of translation. A closing argument is made for a vision of the common that implies neither civilisational harmony nor the translation of all values into a general equivalent. Primary sources include government reports, internet texts and media stories. These are analyzed using techniques of discourse analysis and interpreted with the help of secondary literature concerning globalisation, language and migration. The disciplinary matrix cuts and mixes between cultural studies, translation studies, citizenship studies, globalization studies and

  15. Biomarkers for anorexia nervosa

    DEFF Research Database (Denmark)

    Sjøgren, Jan Magnus

    2017-01-01

    Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization...

  16. Oral Microbiome: A New Biomarker Reservoir for Oral and Oropharyngeal Cancers

    OpenAIRE

    Lim, Yenkai; Totsika, Makrina; Morrison, Mark; Punyadeera, Chamindie

    2017-01-01

    Current biomarkers (DNA, RNA and protein) for oral cavity and oropharyngeal cancers demonstrate biological variations between individuals, rendering them impractical for clinical translation. Whilst these biomarkers originate from the host, there is not much information in the literature about the influence of oral microbiota on cancer pathogenesis, especially in oral cancers. Oral microbiotas are known to participate in disease initiation and progression not only limited to the oral cavity, ...

  17. Amyloid Biomarkers in Conformational Diseases at Face Value: A Systematic Review

    OpenAIRE

    Maria Fernanda Avila-Vazquez; Nelly F. Altamirano-Bustamante; Myriam M. Altamirano-Bustamante

    2017-01-01

    Conformational diseases represent a new aspect of proteomic medicine where diagnostic and therapeutic paradigms are evolving. In this context, the early biomarkers for target cell failure (neurons, β-cells, etc.) represent a challenge to translational medicine and play a multidimensional role as biomarkers and potential therapeutic targets. This systematic review, which follows the PICO and Prisma methods, analyses this new-fangled multidimensionality, its strengths and limitations, and prese...

  18. Biomarkers of cancer cachexia.

    Science.gov (United States)

    Loumaye, Audrey; Thissen, Jean-Paul

    2017-12-01

    Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. However, early diagnosis of cancer cachexia is currently limited for several reasons. Indeed, cachexia development is variable according to tumor and host characteristics. In addition, safe, accessible and non-invasive tools to detect skeletal muscle atrophy are desperately lacking in clinical practice. Finally, the precise molecular mechanisms and the key players involved in cancer cachexia remain poorly characterized. The need for an early diagnosis of cancer cachexia supports therefore the quest for a biomarker that might reflect skeletal muscle atrophy process. Current research offers different promising ways to identify such a biomarker. Initially, the quest for a biomarker of cancer cachexia has mostly focused on mediators of muscle atrophy, produced by both tumor and host, in an attempt to define new therapeutic approaches. In another hand, molecules released by the muscle into the circulation during the atrophy process have been also considered as potential biomarkers. More recently, several "omics" studies are emerging to identify new muscular or circulating markers of cancer cachexia. Some genetic markers could also contribute to identify patients more susceptible to develop cachexia. This article reviews our current knowledge regarding potential biomarkers of cancer cachexia. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  19. Finite translation surfaces with maximal number of translations

    OpenAIRE

    Schlage-Puchta, Jan-Christoph; Weitze-Schmithuesen, Gabriela

    2013-01-01

    The natural automorphism group of a translation surface is its group of translations. For finite translation surfaces of genus g > 1 the order of this group is naturally bounded in terms of g due to a Riemann-Hurwitz formula argument. In analogy with classical Hurwitz surfaces, we call surfaces which achieve the maximal bound Hurwitz translation surfaces. We study for which g there exist Hurwitz translation surfaces of genus g.

  20. Automatic Evaluation of Machine Translation

    DEFF Research Database (Denmark)

    Martinez, Mercedes Garcia; Koglin, Arlene; Mesa-Lao, Bartolomé

    2015-01-01

    The availability of systems capable of producing fairly accurate translations has increased the popularity of machine translation (MT). The translation industry is steadily incorporating MT in their workflows engaging the human translator to post-edit the raw MT output in order to comply with a s...

  1. Advertisement Translation under Skopos Theory

    Institute of Scientific and Technical Information of China (English)

    严妙

    2014-01-01

    This paper is an analysis of advertisement translation under skopos theory.It is explained that the nature of advertisement translation under skopos theory is reconstructing the information of the source text to persuade target audience.Three translation strategies are put forward in translating advertisements.

  2. Translation: Aids, Robots, and Automation.

    Science.gov (United States)

    Andreyewsky, Alexander

    1981-01-01

    Examines electronic aids to translation both as ways to automate it and as an approach to solve problems resulting from shortage of qualified translators. Describes the limitations of robotic MT (Machine Translation) systems, viewing MAT (Machine-Aided Translation) as the only practical solution and the best vehicle for further automation. (MES)

  3. Translational research in medicine

    Directory of Open Access Journals (Sweden)

    Bakir Mehić

    2011-05-01

    Full Text Available Translational medicine is a medical practice based on interventional epidemiology. It is regarded by its proponents as a natural progression from Evidence-Based Medicine. It integrates research from the basic sciences, social sciences and political sciences with the aim of optimizing patient care and preventive measures which may extend beyond healthcare services. In short, it is the process of turning appropriate biological discoveries into drugs and medical devices that can be used in the treatment of patients.[1]Scientific research and the development of modern powerful techniques are crucial for improving patient care in a society that is increasingly demanding the highest quality health services.[2] Indeed, effective patient care requires the continuous improvement of knowledge on the pathophysiology of the diseases, diagnostic procedures and therapeutic tools available. To this end, development of both clinical and basic research in health sciences is required. However, what is most effective in improving medical knowledge, and hence patient care, is the cross-fertilization between basic and clinical science. This has been specifically highlighted in recent years with the coining of the term “translational research”.[3] Translational research is of great importance in all medical specialties.Translational Research is the basis for Translational Medicine. It is the process which leads from evidence based medicine to sustainable solutions for public health problems.[4] It aims to improve the health and longevity of the world’s populations and depends on developing broad-based teams of scientists and scholars who are able to focus their efforts to link basic scientific discoveries with the arena of clinical investigation, and translating the results of clinical trials into changes in clinical practice, informed by evidence from the social and political sciences. Clinical science and ecological support from effective policies can

  4. Engineering in translational medicine

    CERN Document Server

    2014-01-01

    This book covers a broad area of engineering research in translational medicine. Leaders in academic institutions around the world contributed focused chapters on a broad array of topics such as: cell and tissue engineering (6 chapters), genetic and protein engineering (10 chapters), nanoengineering (10 chapters), biomedical instrumentation (4 chapters), and theranostics and other novel approaches (4 chapters). Each chapter is a stand-alone review that summarizes the state-of-the-art of the specific research area. Engineering in Translational Medicine gives readers a comprehensive and in-depth overview of a broad array of related research areas, making this an excellent reference book for scientists and students both new to engineering/translational medicine and currently working in this area.

  5. Quantitative imaging as cancer biomarker

    Science.gov (United States)

    Mankoff, David A.

    2015-03-01

    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

  6. Protein Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: Progress and Challenges.

    Science.gov (United States)

    Root, Alex; Allen, Peter; Tempst, Paul; Yu, Kenneth

    2018-03-07

    Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community. The first set of challenges involves nominating and verifying biomarkers. Candidate biomarkers need to discriminate disease from benign controls with high sensitivity and specificity for an intended use, which we describe as a two-tiered strategy of identifying and screening high-risk patients. Community-wide efforts to share samples, data, and analysis methods have been beneficial and progress meeting this challenge has been achieved. The second set of challenges is assay optimization and validating biomarkers. After initial candidate validation, assays need to be refined into accurate, cost-effective, highly reproducible, and multiplexed targeted panels and then validated in large cohorts. To move the most promising candidates forward, ideally, biomarker panels, head-to-head comparisons, meta-analysis, and assessment in independent data sets might mitigate risk of failure. Much more investment is needed to overcome these challenges. The third challenge is achieving clinical translation. To moonshot an early detection test to the clinic requires a large clinical trial and organizational, regulatory, and entrepreneurial know-how. Additional factors, such as imaging technologies, will likely need to improve concomitant with molecular biomarker development. The magnitude of the clinical translational challenge is uncertain, but interdisciplinary

  7. Protein Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Alex Root

    2018-03-01

    Full Text Available Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community. The first set of challenges involves nominating and verifying biomarkers. Candidate biomarkers need to discriminate disease from benign controls with high sensitivity and specificity for an intended use, which we describe as a two-tiered strategy of identifying and screening high-risk patients. Community-wide efforts to share samples, data, and analysis methods have been beneficial and progress meeting this challenge has been achieved. The second set of challenges is assay optimization and validating biomarkers. After initial candidate validation, assays need to be refined into accurate, cost-effective, highly reproducible, and multiplexed targeted panels and then validated in large cohorts. To move the most promising candidates forward, ideally, biomarker panels, head-to-head comparisons, meta-analysis, and assessment in independent data sets might mitigate risk of failure. Much more investment is needed to overcome these challenges. The third challenge is achieving clinical translation. To moonshot an early detection test to the clinic requires a large clinical trial and organizational, regulatory, and entrepreneurial know-how. Additional factors, such as imaging technologies, will likely need to improve concomitant with molecular biomarker development. The magnitude of the clinical translational challenge is uncertain, but

  8. Data format translation routines

    International Nuclear Information System (INIS)

    Burris, R.D.

    1981-02-01

    To enable the effective connection of several dissimilar computers into a network, modification of the data being passed from one computer to another may become necessary. This document describes a package of routines which permit the translation of data in PDP-8 formats to PDP-11 or DECsystem-10 formats or from PDP-11 format to DECsystem-10 format. Additional routines are described which permit the effective use of the translation routines in the environment of the Fusion Energy Division (FED) network and the Elmo Bumpy Torus (EBT) data base

  9. Translating BPEL to FLOWer

    DEFF Research Database (Denmark)

    Lassen, Kristian Bisgaard

    FLOWer is a case handling tool made by Pallas-Athena for process management in the service industry. BPEL on the other hand is a language for web service orchestration, and has become a de facto standard, because of its popularity, for specifying workflow processes even though that was not its...... original purpose. This paper describe an approach translating BPLE to FLOWer, or more precisely form BPEL to CHIP. where CHIP is the interchange language that FLOWer import from and export to. The aim of the translation scheme that I give is to derive a CHIP specification that is behaviorally equivalent...

  10. Biomarkers of Pediatric Brain Tumors

    Directory of Open Access Journals (Sweden)

    Mark D Russell

    2013-03-01

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

  11. Lessons for tumor biomarker trials: vicious cycles, scientific method & developing guidelines.

    Science.gov (United States)

    Hayes, Daniel; Raison, Claire

    2015-02-01

    Interview with Daniel Hayes, by Claire Raison (Commissioning Editor) Daniel F Hayes, M.D. is the Stuart A Padnos Professor of Breast Cancer Research and co-Director of the Breast Oncology Program at the University of Michigan Comprehensive Cancer Center (Ann Arbor, MI, USA). Dr Hayes has extensive experience in clinical and translational breast cancer biomarker research, and in drug development and clinical trials. Around 30 years ago, he led the discovery of the circulating breast tumor biomarker, CA15-3, which started his career into further tumor biomarker work. The main thrust of his work since then has been in clinical trials, tumor biomarkers and trying to integrate the two. Dr Hayes is Chair of the Correlative Sciences Committee of the North American Breast Cancer Group (now called the Breast Cancer Steering Committee), and co-chairs the Expert Panel for Tumor Biomarker Practice Guidelines for the American Society of Clinical Oncology.

  12. Word Translation Entropy

    DEFF Research Database (Denmark)

    Schaeffer, Moritz; Dragsted, Barbara; Hvelplund, Kristian Tangsgaard

    This study reports on an investigation into the relationship between the number of translation alternatives for a single word and eye movements on the source text. In addition, the effect of word order differences between source and target text on eye movements on the source text is studied. In p...

  13. George Sigerson: Charcot's translator.

    Science.gov (United States)

    Lyons, J B

    1997-04-01

    Senator George Sigerson (1836-1925), Dublin's first neurologist, was also a significant contributor to Anglo-Irish literature. His medical career and literary accomplishments are outlined, the focus of the article being Sigerson's friendly relationship with Charcot (with whom he corresponded), and whose Leçons sur les maladies du système nerveux he translated.

  14. Intermediation, Brokerage and Translation

    NARCIS (Netherlands)

    Hönke, Jana; Müller, Markus-Michael; Risse, Thomas; Draude, Anke; Börzel, Tanja

    2018-01-01

    Brokerage, a term prominent in the 1960s and 1970s, has returned. A huge literature analyses how brokers and intermediators— such as government officials, heads of non-governmental organization (NGOs), translators, neo-traditional authorities— strategically negotiate flows of resources and political

  15. Made in translation

    Science.gov (United States)

    Chaput, John C.

    2018-03-01

    Evolution of highly functionalized DNA could enable the discovery of artificial nucleic acid sequences with different properties to natural DNA. Now, an artificial translation system has been designed that can support the evolution of non-natural sequence-defined nucleic acid polymers carrying eight different functional groups on 32 codons.

  16. Novel biomarkers for sepsis

    DEFF Research Database (Denmark)

    Larsen, Frederik Fruergaard; Petersen, J Asger

    2017-01-01

    BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...

  17. [Biomarkers of Alzheimer disease].

    Science.gov (United States)

    Rachel, Wojciech; Grela, Agatha; Zyss, Tomasz; Zieba, Andrzej; Piekoszewski, Wojciech

    2014-01-01

    Cognitive impairment is one of the most abundant age-related psychiatric disorders. The outcome of cognitive impairment in Alzheimer's disease has both individual (the patients and their families) and socio-economic effects. The prevalence of Alzheimer's disease doubles after the age of 65 years, every 4.5 years. An etiologically heterogenic group of disorders related to aging as well as genetic and environmental interactions probably underlie the impairment in Alzheimer's disease. Those factors cause the degeneration of brain tissue which leads to significant cognitive dysfunction. There are two main hypotheses that are linked to the process of neurodegeneration: (i) amyloid cascade and (ii) the role of secretases and dysfunction of mitochondria. From the therapeutic standpoint it is crucial to get an early diagnosis and start with an adequate treatment. The undeniable progress in the field of biomarker research should lead to a better understanding of the early stages of the disorder. So far, the best recognised and described biomarkers of Alzheimer's disease, which can be detected in both cerebrospinal fluid and blood, are: beta-amyloid, tau-protein and phosphorylated tau-protein (phospho-tau). The article discusses the usefulness of the known biomarkers of Alzheimer's disease in early diagnosis.

  18. Application of proteomics to translational research

    International Nuclear Information System (INIS)

    Liotta, L.A.; Petricoin, E.; Garaci, E.; De Maria, R.; Belluco, C.

    2009-01-01

    Deriving public benefit from basic biomedical research requires a dedicated and highly coordinated effort between basic scientists, physicians, bioinformaticians, clinical trial coordinators, MD and PhD trainees and fellows, and a host of other skilled participants. The Istituto Superiore di Sanita/George Mason University US-Italy Oncoproteomics program, established in 2005, is a successful example of a synergistic creative collaboration between basic scientists and clinical investigators conducting translational research. This program focuses on the application of the new field of proteomics to three urgent and fundamental clinical needs in cancer medicine: 1.) Biomarkers for early diagnosis of cancer, when it is still treatable, 2.) Individualizing patient therapy for molecular targeted inhibitors that block signal pathways driving cancer pathogenesis and 3.) Cancer Progenitor Cells (CSCs): When do the lethal progenitors of cancer first emerge, and how can we treat these CSCs with molecular targeted inhibitors

  19. Translating basic research in cancer patient care

    Directory of Open Access Journals (Sweden)

    Marcello Maugeri-Saccà

    2011-01-01

    Full Text Available With the advent of molecular targeted therapies and the development of high-throughput biotechnologies, it has become evident that progress in cancer research is largely due to the creation of multidisciplinary teams able to plan clinical trials supported by appropriate molecular hypotheses. These efforts have culminated in the identification and validation of biomarkers predictive of response, as well as in the generation of more accurate prognostic tools. The identification of cancer stem cells has provided further insights into mechanisms of cancer, and many studies have tried to translate this biological notion into prognostic and predictive information. In this regard, new agents targeting key stemness-related pathways have entered the clinical development, and preliminary data suggested an encouraging antitumor activity.

  20. Biomarkers in critical illness: have we made progress?

    Directory of Open Access Journals (Sweden)

    Honore PM

    2016-10-01

    Full Text Available Patrick M Honore,1 Rita Jacobs,1 Inne Hendrickx,1 Elisabeth De Waele,1 Viola Van Gorp,1 Olivier Joannes-Boyau,2 Jouke De Regt,1 Willem Boer,3 Herbert D Spapen1 1Intensive Care Unit, Universitair Ziekenhuis Brussel, VUB University, Brussels, Belgium; 2Intensive Care Unit, Hopital Haut Leveque, University of Bordeaux 2, Bordeaux, France; 3Intensive Care Unit, Ziekenhuis Oost-Limburg, Genk, Belgium Abstract: Biomarkers have emerged as exemplary key players in translational medicine. Many have been assessed for timely recognition, early treatment, and adequate follow-up for a variety of pathologies. Biomarker sensitivity has improved considerably over the last years but specificity remains poor, in particular when two “marker-sensitive” conditions overlap in one patient. Biomarker research holds an enormous potential for diagnostic and prognostic purposes in postoperative and critically ill patients who present varying degrees of inflammation, infection, and concomitant (subacute organ dysfunction or failure. Despite a remarkable progress in development and testing, biomarkers are not yet ready for routine use at the bedside. Keywords: biomarkers, acute kidney injury, sepsis, ARDS

  1. COPD Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry.

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    Full Text Available Acute exacerbations of chronic obstructive pulmonary disease (AECOPD result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD.We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72. Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate 1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel was then tested in two independent AECOPD cohorts (Cohort B, n = 37, and Cohort C, n = 109 using leave-pair-out cross-validation methods.Five proteins were identified distinguishing AECOPD and convalescent states in Cohort A. Biomarker scores derived from this model were significantly higher during AECOPD than in the convalescent state in the discovery cohort (p<0.001. The receiver operating characteristic cross-validation area under the curve (CV-AUC statistic was 0.73 in Cohort A, while in the replication cohorts the CV-AUC was 0.77 for Cohort B and 0.79 for Cohort C.A panel of five biomarkers shows promise in distinguishing AECOPD from convalescence and may provide the basis for a clinical blood test to diagnose AECOPD. Further validation in larger cohorts is necessary for future clinical translation.

  2. Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Giovanni Nardo

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments.We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC, a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%, and from patients with neurological disorders that may resemble ALS (91%, between two levels of disease severity (90%, and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing.Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms.

  3. Biomarkers in Diabetic Retinopathy

    Science.gov (United States)

    Jenkins, Alicia J.; Joglekar, Mugdha V.; Hardikar, Anandwardhan A.; Keech, Anthony C.; O'Neal, David N.; Januszewski, Andrzej S.

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  4. Biomarkers in Diabetic Retinopathy.

    Science.gov (United States)

    Jenkins, Alicia J; Joglekar, Mugdha V; Hardikar, Anandwardhan A; Keech, Anthony C; O'Neal, David N; Januszewski, Andrzej S

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  5. On Deletion of Sutra Translation

    Institute of Scientific and Technical Information of China (English)

    CHEN Shu-juan

    2017-01-01

    Dao An's the metaphor of translation "wine diluted with water' ' expressed a view about translation that had been abridged.Later Kumarajiva provided metaphor "rice chewed—tasteless and downright disgusting".Both of them felt regretted at the weakening of taste,sometimes even the complete loss of flavor caused by deletion in translation of Buddhist sutras.In early sutra translation,deletion is unavoidable which made many sutra translators felt confused and drove them to study it further and some even managed to give their understanding to this issue.This thesis will discuss the definition,and what causes deletion and the measures adopted by the sutra translators.

  6. The Impact of Machine Translation and Computer-aided Translation on Translators

    Science.gov (United States)

    Peng, Hao

    2018-03-01

    Under the context of globalization, communications between countries and cultures are becoming increasingly frequent, which make it imperative to use some techniques to help translate. This paper is to explore the influence of computer-aided translation on translators, which is derived from the field of the computer-aided translation (CAT) and machine translation (MT). Followed by an introduction to the development of machine and computer-aided translation, it then depicts the technologies practicable to translators, which are trying to analyze the demand of designing the computer-aided translation so far in translation practice, and optimize the designation of computer-aided translation techniques, and analyze its operability in translation. The findings underline the advantages and disadvantages of MT and CAT tools, and the serviceability and future development of MT and CAT technologies. Finally, this thesis probes into the impact of these new technologies on translators in hope that more translators and translation researchers can learn to use such tools to improve their productivity.

  7. Predictive Biomarkers for Asthma Therapy.

    Science.gov (United States)

    Medrek, Sarah K; Parulekar, Amit D; Hanania, Nicola A

    2017-09-19

    Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

  8. (Con)figuring gender in Bible translation: Cultural, translational and ...

    African Journals Online (AJOL)

    The gendered intersection of cultural studies and Bible translation is under acknowledged. Accounting for gender criticism in translation work requires, besides responsible theory and practice of translation, also attention to interwoven gender critical aspects. After a brief investigation of the intersections between biblical, ...

  9. Translation in Language Teaching: Insights from Professional Translator Training

    Science.gov (United States)

    Carreres, Angeles; Noriega-Sanchez, Maria

    2011-01-01

    The past three decades have seen vast changes in attitudes towards translation, both as an academic discipline and as a profession. The insights we have gained in recent years, in particular in the area of professional translator training, call for a reassessment of the role of translation in language teaching. Drawing on research and practices in…

  10. Translation and identity: Translation of the Freedom Charter into ...

    African Journals Online (AJOL)

    A comparative analysis of the Afrikaans translations reveals how the respective translators struggled sporadically through certain ideological constraints in order to provide a satisfactory narrative. Their inability to internalise the principles contained in the Freedom Charter resulted in them presenting a 'framed' translation ...

  11. A Writer's Thoughts on Translation and Always Living in Translation.

    Science.gov (United States)

    Agosin, Marjorie; Jones, Robin

    2000-01-01

    Discusses how it feels to be a poet who writes in Spanish and has her work translated, examining the author's immigration experiences and noting the translator's contributions in making her work accessible across languages, borders, and cultures. Explains that writing in Spanish is a gesture of survival, and translation allows her memories to…

  12. 'Inhabiting' the Translator's Habitus – Antjie Krog as Translator ...

    African Journals Online (AJOL)

    Drawing on the Bourdieusian concept of habitus and its applicability in the field of translation, this article discusses Antjie Krog's profile in the practice of translation in. South Africa. Bourdieu's conceptualisation of the relationship between the initiating activities of translators and the structures which constrain and enable ...

  13. Translating a wicked problem

    DEFF Research Database (Denmark)

    Tietjen, Anne; Jørgensen, Gertrud

    2016-01-01

    , place-based and project-oriented process directed at concrete physical outcomes. We frame strategic planning as a translation process where the interaction between human and non-human actors translates a unique, complex and contested situation into an innovated situation. We find that local physical...... on the case of a Danish planning process which was carried out in collaboration with a charitable trust, this paper discusses an emerging strategic planning approach at the municipal level. We use the concept of wicked problems, strategic planning theory and Actor-Network-Theory to study a collaborative...... projects played a major role in this process. First, they acted as a vehicle that assembled planners, politicians and stakeholders to work towards strategic visions across multiple scales. Second and consequently, they stimulated considerable second and third order effects in the form of shared problem...

  14. Structural Coupling and Translation

    DEFF Research Database (Denmark)

    Tække, Jesper

    formations. After presenting the two theories the article put forward Twitter as an example making it possible to compare the two theories. Hereby the article also provides two analysis of how Twitter changes the communication milieu of modern society. In systems theory media can be seen as the mechanisms...... and translations the social medium of Twitter opens for. The second, but most prioritized, aim of the paper is to present, compare and discuss the two theories: How do they understand what becomes visible in their different optics, which observations become possible in the one or the other – and is it possible...... creating networks consisting in both humans and non-humans. Then the two appearing frameworks are used to observe Twitter and discuss which structural couplings and translations are made possible by this medium. In the end of the paper the two theories are discussed and compared....

  15. Translation of Financial Statements

    OpenAIRE

    Dalthan Simas; Otavio De Medeiros

    2005-01-01

    This paper has the purpose of surveying and critically analyzing the effects of accounting procedures which are closely related to groups of companies operating multinationally. These are the methods for translation of financial statements, e.g. the Temporal and the Closing- rate Methods, as far as those methods are embodied in accounting standards which have been either recommended or adopted by countries such as the UK and US. We conclude that with regard to changing prices, General Price L...

  16. CADAT network translator

    Science.gov (United States)

    Pitts, E. R.

    1981-01-01

    Program converts cell-net data into logic-gate models for use in test and simulation programs. Input consists of either Place, Route, and Fold (PRF) or Place-and-Route-in-Two-Dimensions (PR2D) layout data deck. Output consists of either Test Pattern Generator (TPG) or Logic-Simulation (LOGSIM) logic circuitry data deck. Designer needs to build only logic-gate-model circuit description since program acts as translator. Language is FORTRAN IV.

  17. Repetition and Translation Shifts

    Directory of Open Access Journals (Sweden)

    Simon Zupan

    2006-06-01

    Full Text Available Repetition manifests itself in different ways and at different levels of the text. The first basic type of repetition involves complete recurrences; in which a particular textual feature repeats in its entirety. The second type involves partial recurrences; in which the second repetition of the same textual feature includes certain modifications to the first occurrence. In the article; repetitive patterns in Edgar Allan Poe’s short story “The Fall of the House of Usher” and its Slovene translation; “Konec Usherjeve hiše”; are compared. The author examines different kinds of repetitive patterns. Repetitions are compared at both the micro- and macrostructural levels. As detailed analyses have shown; considerable microstructural translation shifts occur in certain types of repetitive patterns. Since these are not only occasional; sporadic phenomena; but are of a relatively high frequency; they reduce the translated text’s potential for achieving some of the gothic effects. The macrostructural textual property particularly affected by these shifts is the narrator’s experience as described by the narrative; which suffers a reduction in intensity.

  18. Translation-Memory (TM) Research

    DEFF Research Database (Denmark)

    Schjoldager, Anne Gram; Christensen, Tina Paulsen

    2010-01-01

    to be representative of the research field as a whole. Our analysis suggests that, while considerable knowledge is available about the technical side of TMs, more research is needed to understand how translators interact with TM technology and how TMs influence translators' cognitive translation processes.......  It is no exaggeration to say that the advent of translation-memory (TM) systems in the translation profession has led to drastic changes in translators' processes and workflow, and yet, though many professional translators nowadays depend on some form of TM system, this has not been the object...... of much research. Our paper attempts to find out what we know about the nature, applications and influences of TM technology, including translators' interaction with TMs, and also how we know it. An essential part of the analysis is based on a selection of empirical TM studies, which we assume...

  19. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  20. Biomarker Identification Using Text Mining

    Directory of Open Access Journals (Sweden)

    Hui Li

    2012-01-01

    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.

  1. Chiral Biomarkers in Meteorites

    Science.gov (United States)

    Hoover, Richard B.

    2010-01-01

    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

  2. Machine Translation Effect on Communication

    DEFF Research Database (Denmark)

    Jensen, Mika Yasuoka; Bjørn, Pernille

    2011-01-01

    Intercultural collaboration facilitated by machine translation has gradually spread in various settings. Still, little is known as for the practice of machine-translation mediated communication. This paper investigates how machine translation affects intercultural communication in practice. Based...... on communication in which multilingual communication system is applied, we identify four communication types and its’ influences on stakeholders’ communication process, especially focusing on establishment and maintenance of common ground. Different from our expectation that quality of machine translation results...

  3. TEACHING TRANSLATION: OBJECTIVES AND METHODS

    OpenAIRE

    Kobyakova, Iryna; Shvachko, Svitlana

    2016-01-01

    The article is focused on the set of items: teaching translation, objectives, exercises and assignments (both word-centered and text-centered translation), translation analysis. The choice of the items is motivated by the dominant functions of transatology (nominative and communicative). The latter succeed in identification of adequate, congruent, equivalent translation. The article discusses the problems of professional validity, theoretical insertions, textocentric analysis. Gains, achievem...

  4. Shoulder surgery in the beach chair position is associated with diminished cerebral autoregulation but no differences in postoperative cognition or brain injury biomarker levels compared with supine positioning: the anesthesia patient safety foundation beach chair study.

    Science.gov (United States)

    Laflam, Andrew; Joshi, Brijen; Brady, Kenneth; Yenokyan, Gayane; Brown, Charles; Everett, Allen; Selnes, Ola; McFarland, Edward; Hogue, Charles W

    2015-01-01

    Although controversial, failing to consider the gravitational effects of head elevation on cerebral perfusion is speculated to increase susceptibility to rare, but devastating, neurologic complications after shoulder surgery in the beach chair position (BCP). We hypothesized that patients in the BCP have diminished cerebral blood flow autoregulation than those who undergo surgery in the lateral decubitus position (LDP). A secondary aim was to examine whether there is a relationship between patient positioning during surgery and postoperative cognition or serum brain injury biomarker levels. Patients undergoing shoulder surgery in the BCP (n = 109) or LDP (n = 109) had mean arterial blood pressure (MAP) and regional cerebral oxygen saturation (rScO2) monitored with near-infrared spectroscopy. A continuous, moving Pearson correlation coefficient was calculated between MAP and rScO2, generating the variable cerebral oximetry index (COx). When MAP is in the autoregulated range, COx approaches zero because there is no correlation between cerebral blood flow and arterial blood pressure. In contrast, when MAP is below the limit of autoregulation, COx is higher because there is a direct relationship between lower arterial blood pressure and lower cerebral blood flow. Thus, diminished autoregulation would be manifest as higher COx. Psychometric testing was performed before surgery and then 7 to 10 days and 4 to 6 weeks after surgery. A composite cognitive outcome was determined as the Z-score. Serum S100β, neuron-specific enolase, and glial fibrillary acidic protein were measured at baseline, after surgery, and on postoperative day 1. After adjusting for age and history of hypertension, COx (P = 0.035) was higher and rScO2 lower (P surgery between the BCP and the LDP groups. There was no difference in serum biomarker levels between the 2 position groups : Compared with patients in the LDP, patients undergoing shoulder surgery in the BCP are more likely to have higher COx

  5. Hepcidin- A Burgeoning Biomarker

    Directory of Open Access Journals (Sweden)

    Hemkant Manikrao Deshmukh

    2017-10-01

    Full Text Available The discovery of hepcidin has triggered a virtual ignition of studies on iron metabolism and related disorders. The peptide hormone hepcidin is a key homeostatic regulator of iron metabolism. The synthesis of hepcidin is induced by systemic iron levels and by inflammatory stimuli. Several human diseases are associated with variations in hepcidin concentrations. The evaluation of hepcidin in biological fluids is therefore a promising device in the diagnosis and management of medical situations in which iron metabolism is affected. Thus, it made us to recapitulate role of hepcidin as biomarker.

  6. 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...... with very specific competencies. In order to optimize the basis of a sound and fruitful data analysis, suggestions are givenwhich focus on (1) collection of good data, (2) preparation of data for the data analysis and (3) a sound data analysis. If these steps are optimized, PLS is a also a very goodmethod...

  7. On Literal Translation of English Idioms

    Science.gov (United States)

    Chen, Linli

    2009-01-01

    There are six translation tactics in translating English idioms into Chinese: literal translation, compensatory translation, free translation, explanational translation, borrowing, integrated approach. Each tactic should be reasonably employed in the process of translating, so as to keep the flavor of the original English idioms as well as to…

  8. Translational Implications of Tamil "Hamlets."

    Science.gov (United States)

    Kanakaraj, S.

    1994-01-01

    Discusses the use of translation when teaching English as a Second Language in a Tamil context. Singles out the fencing episode in Shakespeare's "Hamlet" to illustrate the difficulties of translating cultural aspects. Concludes that successful translations of Shakespeare into Indian languages should involve collaboration between…

  9. MULTIFUNCTION OF INTERNET IN TRANSLATION

    Directory of Open Access Journals (Sweden)

    Bayu Budiharjo

    2017-04-01

    Full Text Available Technology affects almost all areas, including translation. Many products of technology have made translational works easier, one of which is internet. Despite the wide use of internet, the potentials it has are sometimes unnoticed. While web-based dictionaries or thesaurus often serve as translators’ assistants and online Machine Translation issues become topics of many researches, other uses of internet related to translation may not be known by many. Internet can help disseminate newborn ideas, theories and findings worldwide to enhance translation theories. Besides, the contact between internet and translation generates new areas to examine. Internet also provides helping hand in the area of translation research. Researcher or anyone conducting research in the field of translation can find a range of research gaps as well as reference. Those who need group discussions to collect required data from informants, or researchers of the same interest coming from all over the world can meet and conduct Focus Group Discussion (FGD on virtual world. Furthermore, internet offers various forms of assistance for translation practitioners. The commonly used internet assistance consists of dictionaries, thesaurus and Machine Translations available on the internet. Other forms of aid provided by internet take form of parallel texts, images, and videos, which can be very helpful. Internet provides many things which can be utilized for the purpose of translation. Internet keeps on providing more as it develops from time to time in line with the development of technology. Internet awaits utilization of theorists, researchers, practitioners and those having concern on translation.

  10. Machine Translation for Academic Purposes

    Science.gov (United States)

    Lin, Grace Hui-chin; Chien, Paul Shih Chieh

    2009-01-01

    Due to the globalization trend and knowledge boost in the second millennium, multi-lingual translation has become a noteworthy issue. For the purposes of learning knowledge in academic fields, Machine Translation (MT) should be noticed not only academically but also practically. MT should be informed to the translating learners because it is a…

  11. Translational plant proteomics: A perspective

    NARCIS (Netherlands)

    Agrawal, G.K.; Pedreschi, R.; Barkla, B.J.; Bindschedler, L.V.; Cramer, R.; Sarkar, A.; Renaut, J.; Job, D.; Rakwal, R.

    2012-01-01

    Translational proteomics is an emerging sub-discipline of the proteomics field in the biological sciences. Translational plant proteomics aims to integrate knowledge from basic sciences to translate it into field applications to solve issues related but not limited to the recreational and economic

  12. Lexical Discourse Analysis in Translation

    Science.gov (United States)

    Al Khotaba, Eissa; Al Tarawneh, Khaled

    2015-01-01

    Lexical Discourse very often depend on lexis. Lexical Discourse analysis, however, has not yet been given enough consideration of the phenomenon of translation. This paper investigates lexical discourse analysis in translation from one language to another. This qualitative study comprises 15 text translated by M.A. students at the Department of…

  13. Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study

    DEFF Research Database (Denmark)

    Lajer, C B; Nielsen, F C; Friis-Hansen, L

    2011-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs, which regulate mRNA translation/decay, and may serve as biomarkers. We characterised the expression of miRNAs in clinically sampled oral and pharyngeal squamous cell carcinoma (OSCC and PSCC) and described the influence of human papilloma virus (HPV)....

  14. Machine Translation Tools - Tools of The Translator's Trade

    DEFF Research Database (Denmark)

    Kastberg, Peter

    2012-01-01

    In this article three of the more common types of translation tools are presented, discussed and critically evaluated. The types of translation tools dealt with in this article are: Fully Automated Machine Translation (or FAMT), Human Aided Machine Translation (or HAMT) and Machine Aided Human...... Translation (or MAHT). The strengths and weaknesses of the different types of tools are discussed and evaluated by means of a number of examples. The article aims at two things: at presenting a sort of state of the art of what is commonly referred to as “machine translation” as well as at providing the reader...... with a sound basis for considering what translation tool (if any) is the most appropriate in order to meet his or her specific translation needs....

  15. Translating gene transfer: a stalled effort.

    Science.gov (United States)

    Greenberg, Alexandra J; McCormick, Jennifer; Tapia, Carmen J; Windebank, Anthony J

    2011-08-01

    The journey of gene transfer from laboratory to clinic has been slow and fraught with many challenges and barriers. Despite the development of the initial technology in the early 1970s, a standard clinical treatment involving "gene therapy" remains to be seen. Furthermore, much was written about the technology in the early 1990s, but since then, not much has been written about the journey of gene transfer. The translational path of gene transfer thus far, both pitfalls and successes, can serve as a study not only in navigating ethical and safety concerns, but also in the importance of scientist-public interactions. Here, we examine the translational progress of gene transfer and what can be gleaned from its history. © 2011 Wiley Periodicals, Inc.

  16. Seismic analysis for translational failure of landfills with retaining walls.

    Science.gov (United States)

    Feng, Shi-Jin; Gao, Li-Ya

    2010-11-01

    In the seismic impact zone, seismic force can be a major triggering mechanism for translational failures of landfills. The scope of this paper is to develop a three-part wedge method for seismic analysis of translational failures of landfills with retaining walls. The approximate solution of the factor of safety can be calculated. Unlike previous conventional limit equilibrium methods, the new method is capable of revealing the effects of both the solid waste shear strength and the retaining wall on the translational failures of landfills during earthquake. Parameter studies of the developed method show that the factor of safety decreases with the increase of the seismic coefficient, while it increases quickly with the increase of the minimum friction angle beneath waste mass for various horizontal seismic coefficients. Increasing the minimum friction angle beneath the waste mass appears to be more effective than any other parameters for increasing the factor of safety under the considered condition. Thus, selecting liner materials with higher friction angle will considerably reduce the potential for translational failures of landfills during earthquake. The factor of safety gradually increases with the increase of the height of retaining wall for various horizontal seismic coefficients. A higher retaining wall is beneficial to the seismic stability of the landfill. Simply ignoring the retaining wall will lead to serious underestimation of the factor of safety. Besides, the approximate solution of the yield acceleration coefficient of the landfill is also presented based on the calculated method. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Biomarkers in Vasculitis

    Science.gov (United States)

    Monach, Paul A.

    2014-01-01

    Purpose of review Better biomarkers are needed for guiding management of patients with vasculitis. Large cohorts and technological advances had led to an increase in pre-clinical studies of potential biomarkers. Recent findings The most interesting markers described recently include a gene expression signature in CD8+ T cells that predicts tendency to relapse or remain relapse-free in ANCA-associated vasculitis, and a pair of urinary proteins that are elevated in Kawasaki disease but not other febrile illnesses. Both of these studies used “omics” technologies to generate and then test hypotheses. More conventional hypothesis-based studies have indicated that the following circulating proteins have potential to improve upon clinically available tests: pentraxin-3 in giant cell arteritis and Takayasu’s arteritis; von Willebrand factor antigen in childhood central nervous system vasculitis; eotaxin-3 and other markers related to eosinophils or Th2 immune responses in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome); and MMP-3, TIMP-1, and CXCL13 in ANCA-associated vasculitis. Summary New markers testable in blood and urine have the potential to assist with diagnosis, staging, assessment of current disease activity, and prognosis. However, the standards for clinical usefulness, in particular the demonstration of either very high sensitivity or very high specificity, have yet to be met for clinically relevant outcomes. PMID:24257367

  18. Critical inquiry and knowledge translation: exploring compatibilities and tensions.

    Science.gov (United States)

    Reimer-Kirkham, Sheryl; Varcoe, Colleen; Browne, Annette J; Lynam, M Judith; Khan, Koushambhi Basu; McDonald, Heather

    2009-07-01

    Knowledge translation has been widely taken up as an innovative process to facilitate the uptake of research-derived knowledge into health care services. Drawing on a recent research project, we engage in a philosophic examination of how knowledge translation might serve as vehicle for the transfer of critically oriented knowledge regarding social justice, health inequities, and cultural safety into clinical practice. Through an explication of what might be considered disparate traditions (those of critical inquiry and knowledge translation), we identify compatibilities and discrepancies both within the critical tradition, and between critical inquiry and knowledge translation. The ontological and epistemological origins of the knowledge to be translated carry implications for the synthesis and translation phases of knowledge translation. In our case, the studies we synthesized were informed by various critical perspectives and hence we needed to reconcile differences that exist within the critical tradition. A review of the history of critical inquiry served to articulate the nature of these differences while identifying common purposes around which to strategically coalesce. Other challenges arise when knowledge translation and critical inquiry are brought together. Critique is one of the hallmark methods of critical inquiry and, yet, the engagement required for knowledge translation between researchers and health care administrators, practitioners, and other stakeholders makes an antagonistic stance of critique problematic. While knowledge translation offers expanded views of evidence and the complex processes of knowledge exchange, we have been alerted to the continual pull toward epistemologies and methods reminiscent of the positivist paradigm by their instrumental views of knowledge and assumptions of objectivity and political neutrality. These types of tensions have been productive for us as a research team in prompting a critical reconceptualization of

  19. Critical inquiry and knowledge translation: exploring compatibilities and tensions

    Science.gov (United States)

    Reimer-Kirkham, Sheryl; Varcoe, Colleen; Browne, Annette J.; Lynam, M. Judith; Khan, Koushambhi Basu; McDonald, Heather

    2016-01-01

    Knowledge translation has been widely taken up as an innovative process to facilitate the uptake of research-derived knowledge into health care services. Drawing on a recent research project, we engage in a philosophic examination of how knowledge translation might serve as vehicle for the transfer of critically oriented knowledge regarding social justice, health inequities, and cultural safety into clinical practice. Through an explication of what might be considered disparate traditions (those of critical inquiry and knowledge translation), we identify compatibilities and discrepancies both within the critical tradition, and between critical inquiry and knowledge translation. The ontological and epistemological origins of the knowledge to be translated carry implications for the synthesis and translation phases of knowledge translation. In our case, the studies we synthesized were informed by various critical perspectives and hence we needed to reconcile differences that exist within the critical tradition. A review of the history of critical inquiry served to articulate the nature of these differences while identifying common purposes around which to strategically coalesce. Other challenges arise when knowledge translation and critical inquiry are brought together. Critique is one of the hallmark methods of critical inquiry and, yet, the engagement required for knowledge translation between researchers and health care administrators, practitioners, and other stakeholders makes an antagonistic stance of critique problematic. While knowledge translation offers expanded views of evidence and the complex processes of knowledge exchange, we have been alerted to the continual pull toward epistemologies and methods reminiscent of the positivist paradigm by their instrumental views of knowledge and assumptions of objectivity and political neutrality. These types of tensions have been productive for us as a research team in prompting a critical reconceptualization of

  20. Mamma Mia, A Singable Translation!

    Directory of Open Access Journals (Sweden)

    Andrej Stopar

    2016-06-01

    Full Text Available The article discusses and analyzes approaches to translating singable texts. It presents a linguistic (prosodic, lexical and structural analysis of the Slovenian translation of the musical Mamma Mia! The aim of the qualitative and quantitative study is to investigate the translation strategies used to produce a singable target text. The results of the analysis suggest that producing a prosodic match is a basic requirement, whereas the lexical, structural and/or poetic characteristics of the source text are subject to changes. Overall, the findings show that the function and the purpose of the translation play a crucial role in the prioritization of translation strategies.

  1. The Complexity of Indirect Translation

    DEFF Research Database (Denmark)

    Wenjie, L. I.

    2017-01-01

    its complex nature, and thus determined that many facets of ITr remain to be studied. The present article will try to encompass the complexity of ITr by looking into the reasons for translating indirectly, the challenge of finding out mediating texts (MTs), indirectness in both translation...... of which have been translated and interpreted indirectly through major languages like English, will be employed as examples. Hopefully, this study will offer more insights into the nature of translation as a social activity and raise further interests in studying translation as a complex phenomenon....

  2. Computer-aided translation tools

    DEFF Research Database (Denmark)

    Christensen, Tina Paulsen; Schjoldager, Anne

    2016-01-01

    in Denmark is rather high in general, but limited in the case of machine translation (MT) tools: While most TSPs use translation-memory (TM) software, often in combination with a terminology management system (TMS), only very few have implemented MT, which is criticised for its low quality output, especially......The paper reports on a questionnaire survey from 2013 of the uptake and use of computer-aided translation (CAT) tools by Danish translation service providers (TSPs) and discusses how these tools appear to have impacted on the Danish translation industry. According to our results, the uptake...

  3. Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Nassirpour, Rounak, E-mail: Rounak.nassirpour@pfizer.com [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States); Ramaiah, Shashi K. [Drug Safety, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139 (United States); Whiteley, Laurence O. [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States)

    2016-12-01

    Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well as their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. - Highlights: • miRNAs are promising biomarkers of drug-induced kidney injury. • Summarized pre-clinical miRNA biomarkers of drug-induced nephrotoxicity. • Described the strengths and challenges associated with miRNAs as biomarkers.

  4. Playground Safety

    Science.gov (United States)

    ... Prevention Fall Prevention Playground Safety Poisoning Prevention Road Traffic Safety Sports Safety Get Email Updates To receive ... at the Consumer Product Safety Commission’s Playground Safety website . References U.S. Consumer Product Safety Commission. Injuries and ...

  5. Translators: Travellers, Not Tourists

    Directory of Open Access Journals (Sweden)

    Veronika Rot Gabrovec

    2015-12-01

    Full Text Available The article explores various representations of culture(s found in contemporary English children’s literature and discusses how they were rendered into Slovene. In the first part, some introductory definitions of culture and approaches to the translation of children’s literature are presented. In the second part, excerpts from selected literary works (for instance, Mary Poppins, Harry Potter and the Philosopher’s Stone, Matilda, The Curious Incident of the Dog in the Night-Time are examined, both from the source and the target texts, with more attention paid to the cultural contexts, and the social changes that possibly influenced the translator’s decisions.

  6. Translation Analysis on Civil Engineering Text Produced by Machine Translator

    Directory of Open Access Journals (Sweden)

    Sutopo Anam

    2018-01-01

    Full Text Available Translation is extremely needed in communication since people have serious problem in the language used. Translation activity is done by the person in charge for translating the material. Translation activity is also able to be done by machine. It is called machine translation, reflected in the programs developed by programmer. One of them is Transtool. Many people used Transtool for helping them in solving the problem related with translation activities. This paper wants to deliver how important is the Transtool program, how effective is Transtool program and how is the function of Transtool for human business. This study applies qualitative research. The sources of data were document and informant. This study used documentation and in dept-interviewing as the techniques for collecting data. The collected data were analyzed by using interactive analysis. The results of the study show that, first; Transtool program is helpful for people in translating the civil engineering text and it functions as the aid or helper, second; the working of Transtool software program is effective enough and third; the result of translation produced by Transtool is good for short and simple sentences and not readable, not understandable and not accurate for long sentences (compound, complex and compound complex thought the result is informative. The translated material must be edited by the professional translator.

  7. PERSONALITY TYPE AND TRANSLATION PERFORMANCE OF PERSIAN TRANSLATOR TRAINEES

    Directory of Open Access Journals (Sweden)

    Reza Shaki

    2017-09-01

    Full Text Available The study investigated the relationship between the personality typology of a sample of Iranian translation students and their translation quality in terms of expressive, appellative, and informative text types. The study also attempted to identify the personality types that can perform better in English to Persian translation of the three text types. For that purpose, the personality type and the translation quality of the participants was assessed using Myers-Briggs Type Indicator (MBTI personality test and translation quality assessment (TQA, respectively. The analysis of the data revealed that the personality type of the participants seemed relevant to the translation quality of all the text types. The translation quality of the participants with intuitive and thinking types was significantly better than the sensing type counterparts in translating expressive texts. The participants with intuitive and feeling types also performed better than their counterparts with sensing type in translation of the informative text. Moreover, the participants with intuitive, feeling, and thinking personality types performed more successfully than the participants with sensing type in translation of the appellative text. The findings of the study are discussed in light of the existing research literature.

  8. Translation Analysis on Civil Engineering Text Produced by Machine Translator

    Science.gov (United States)

    Sutopo, Anam

    2018-02-01

    Translation is extremely needed in communication since people have serious problem in the language used. Translation activity is done by the person in charge for translating the material. Translation activity is also able to be done by machine. It is called machine translation, reflected in the programs developed by programmer. One of them is Transtool. Many people used Transtool for helping them in solving the problem related with translation activities. This paper wants to deliver how important is the Transtool program, how effective is Transtool program and how is the function of Transtool for human business. This study applies qualitative research. The sources of data were document and informant. This study used documentation and in dept-interviewing as the techniques for collecting data. The collected data were analyzed by using interactive analysis. The results of the study show that, first; Transtool program is helpful for people in translating the civil engineering text and it functions as the aid or helper, second; the working of Transtool software program is effective enough and third; the result of translation produced by Transtool is good for short and simple sentences and not readable, not understandable and not accurate for long sentences (compound, complex and compound complex) thought the result is informative. The translated material must be edited by the professional translator.

  9. Magnetic translator bearings

    Science.gov (United States)

    Hockney, Richard L. (Inventor); Downer, James R. (Inventor); Eisenhaure, David B. (Inventor); Hawkey, Timothy J. (Inventor); Johnson, Bruce G. (Inventor)

    1990-01-01

    A magnetic bearing system for enabling translational motion includes a carriage and a shaft for movably supporting the carriage; a first magnetic bearing fixed to one of the carriage and shaft and slidably received in a first channel of the other of the carriage and shaft. The first channel is generally U shaped with two side walls and a back wall. The magnetic bearing includes a pair of spaced magnetic pole pieces, each pole piece having a pair of electromagnetic coils mounted on poles on opposite ends of the pole piece proximate the side walls, and a third electromagnetic coil mounted on a pole of the pole piece proximate the backwall; a motion sensor for sensing translational motion along two axes and rotationally about three axes of the carriage and shaft relative to each other; and a correction circuit responsive to the sensor for generating a correction signal to drive the coils to compensate for any misalignment sensed between the carriage and the shaft.

  10. National Science and Technology Institute for Translational Medicine (INCT-TM): advancing the field of translational medicine and mental health.

    Science.gov (United States)

    Hallak, Jaime E C; Crippa, José Alexandre S; Quevedo, João; Roesler, Rafael; Schröder, Nadja; Nardi, Antonio Egidio; Kapczinski, Flávio

    2010-03-01

    Translational medicine has been described as the integrated application of innovative pharmacology tools, biomarkers, clinical methods, clinical technologies and study designs to improve the understanding of medical disorders. In medicine, translational research offers an opportunity for applying the findings obtained from basic research to every-day clinical applications. The National Science and Technology Institute for Translational Medicine is comprised of six member institutions (Universidade Federal do Rio Grande do Sul, Universidade de São Paulo-Ribeirão Preto, Universidade Federal do Rio de Janeiro, Pontifícia Universidade Católica do Rio Grande do Sul, Universidade Estadual de Santa Catarina and a core facility that serves all centers). The objectives of the project are divided into four areas: Institutional, Research, Human Resources and Technology for the Community and Productive Sector. In this manuscript, we describe some of the approaches used to attain the main objectives of the National Science and Technology Institute for Translational Medicine, which include the development of 1) animal models for bipolar disorder; 2) strategies to investigate neurobehavioral function and cognitive dysfunction associated with brain disorders; 3) experimental models of brain function and behavior, neuropsychiatric disorders, cell proliferation, and cancer; 4) Simulated Public Speaking and 5) Virtual reality simulation for inducing panic disorder and agoraphobia. The main focus of the National Science and Technology Institute for Translational Medicine is the development of more useful methods that allow for a better application of basic research-based knowledge to the medical field.

  11. National Center for Advancing Translational Sciences

    Science.gov (United States)

    ... Models Core Technologies Clinical Innovation Clinical and Translational Science Awards Program Rare Diseases Clinical Research Network Patient ... to our monthly e-newsletter. About Translation Translational Science Spectrum Explore the full spectrum of translational science, ...

  12. [Autoantibodies as biomarkers].

    Science.gov (United States)

    Tron, François

    2014-01-01

    Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process. They often constitute biomarkers of autoimmune diseases and are measured by tests displaying various diagnosis sensitivity and specificity. Autoantibody titers can be correlated to the disease activity and certain autoantibody populations associated with particular clinical manifestations or tissue lesions. The demonstration that autoantibodies appear years before the onset of autoimmune diseases indicates that their presence in healthy individuals may be a predictive marker of the occurrence of disease. Certain autoantibodies could also be predictive markers of a therapeutic response to biologics and of the occurrence of side effects as well. Thus, autoantibodies are useful tools in the diagnosis and the management of patients with organ specific or non-organ specific autoimmune diseases at different steps of the autoimmune process. Copyright © 2013. Published by Elsevier Masson SAS.

  13. Biomarkers of adverse drug reactions.

    Science.gov (United States)

    Carr, Daniel F; Pirmohamed, Munir

    2018-02-01

    Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

  14. New biomarkers for sepsis

    Directory of Open Access Journals (Sweden)

    Li-xin XIE

    2013-01-01

    Full Text Available There is a higher sepsis rate in the intensive care unit (ICU patients, which is one of the most important causes for patient death, but the sepsis lacks specific clinical manifestations. Exploring sensitive and specific molecular markers for infection that accurately reflect infection severity and prognosis is very clinically important. In this article, based on our previous study, we introduce some new biomarkers with high sensitivity and specificity for the diagnosis and predicting the prognosis and severity of sepsis. Increase of serum soluble(s triggering receptor expressed on myeloid cells-1 (sTREM-1 suggests a poor prognosis of septic patients, and changes of locus rs2234237 of sTREM-1 may be the one of important mechanisms. Additionally, urine sTREM-1 can provide an early warning of possible secondary acute kidney injury (AKI in sepsis patients. Serum sCD163 level was found to be a more important factor than procalcitonin (PCT and C-reactive protein (CRP in prognosis of sepsis, especially severe sepsis. Moreover, urine sCD163 also shows excellent performance in the diagnosis of sepsis and sepsis-associated AKI. Circulating microRNAs, such as miR-150, miR-297, miR-574-5p, miR -146a , miR-223, miR -15a and miR-16, also play important roles in the evaluation of status of septic patients. In the foreseeable future, newly-emerging technologies, including proteomics, metabonomics and trans-omics, may exert profound effects on the discovery of valuable biomarkers for sepsis.

  15. Translation goes to the movies

    CERN Document Server

    Cronin, Michael

    2008-01-01

    This highly accessible introduction to translation theory, written by a leading author in the field, uses the genre of film to bring the main themes in translation to life. Through analyzing films as diverse as the Marx Brothers' A Night at the Opera, The Star Wars Trilogies and Lost in Translation, the reader is encouraged to think about both issues and problems of translation as they are played out on the screen and issues of filmic representation through examining the translation dimension of specific films. In highlighting how translation has featured in both mainstream commercial and arthouse films over the years, Cronin shows how translation has been a concern of filmmakers dealing with questions of culture, identity, conflict and representation. This book is a lively and accessible text for translation theory courses and offers a new and largely unexplored approach to topics of identity and representation on screen. Translation Goes to the Movies will be of interest to those on translation studies...

  16. Pauses by Student and Professional Translators in Translation Process

    Directory of Open Access Journals (Sweden)

    Rusdi Noor Rosa

    2018-01-01

    Full Text Available Translation as a process of meaning making activity requires a cognitive process one of which is realized in a pause, a temporary stop or a break indicating doing other than typing activities in a certain period of translation process. Scholars agree that pauses are an indicator of cognitive process without which there will never be any translation practices. Despite such agreement, pauses are debatable as well, either in terms of their length or in terms of the activities managed by a translator while taking pauses. This study, in particular, aims at finding out how student translators and professional translators managed the pauses in a translation process. This was a descriptive research taking two student translators and two professional translators as the participants who were asked to translate a text from English into bahasa Indonesia. The source text (ST was a historical recount text entitled ‘Early History of Yellowstone National Park’ downloaded from http://www.nezperce.com/yelpark9.html composed of 230-word long from English into bahasa Indonesia. The data were collected using Translog protocols, think aloud protocols (TAPs and screen recording. Based on the data analysis, it was found that student translators took the longest pauses in the drafting phase spent to solve the problems related to finding out the right equivalent for the ST words or terms and to solve the difficulties encountered in encoding their ST understanding in the TL; meanwhile, professional translators took the longest pauses in the pos-drafting phase spent to ensure whether their TT had been natural and whether their TT had corresponded to the prevailing grammatical rules of the TL.

  17. Topical Review: Translating Translational Research in Behavioral Science.

    Science.gov (United States)

    Hommel, Kevin A; Modi, Avani C; Piazza-Waggoner, Carrie; Myers, James D

    2015-01-01

    To present a model of translational research for behavioral science that communicates the role of behavioral research at each phase of translation. A task force identified gaps in knowledge regarding behavioral translational research processes and made recommendations regarding advancement of knowledge. A comprehensive model of translational behavioral research was developed. This model represents T1, T2, and T3 research activities, as well as Phase 1, 2, 3, and 4 clinical trials. Clinical illustrations of translational processes are also offered as support for the model. Behavioral science has struggled with defining a translational research model that effectively articulates each stage of translation and complements biomedical research. Our model defines key activities at each phase of translation from basic discovery to dissemination/implementation. This should be a starting point for communicating the role of behavioral science in translational research and a catalyst for better integration of biomedical and behavioral research. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. An Evergreen Challenge for Translators – The Translation of Idioms

    Directory of Open Access Journals (Sweden)

    Kovács Gabriella

    2016-12-01

    Full Text Available Translating idioms has always been a challenging decision-making process for translators mainly because not all idioms have direct equivalents in the target language. Translators usually and ideally have a solid knowledge of the target language and its cultural aspects, but even so they cannot match the ability of a native speaker in deciding when – i.e. in what context and text type – an idiom would or would not be appropriate. This study aims to explore the main characteristics of idioms and the difficulties which might occur when translating them. A needs analysis will also be presented, where the various solutions which a group of translator trainees chose while translating certain idioms from the novel “A Game of Thrones” by George R. R. Martin into Hungarian are examined. Their strategies and the appropriateness of their choices are analysed and compared with the options of the experienced literary translator (Tamás Pétersz. We consider this an important endeavour because, based on our experience, we believe that the topic of the translation of idioms should be included into the curriculum and appropriate materials and tasks should be designed to develop the translator trainees’ knowledge and skills in this domain. Therefore, the aim of this analysis is to obtain a clearer view of the difficulties they are dealing with and bear them in mind when designing teaching materials for them.

  19. New developments and concepts related to biomarker application to vaccines

    Science.gov (United States)

    Ahmed, S. Sohail; Black, Steve; Ulmer, Jeffrey

    2012-01-01

    Summary This minireview will provide a perspective on new developments and concepts related to biomarker applications for vaccines. In the context of preventive vaccines, biomarkers have the potential to predict adverse events in select subjects due to differences in genetic make‐up/underlying medical conditions or to predict effectiveness (good versus poor response). When expanding them to therapeutic vaccines, their utility in identification of patients most likely to respond favourably (or avoid potentially negative effects of treatment) becomes self‐explanatory. Despite the progress made so far on dissection of various pathways of biological significance in humans, there is still plenty to unravel about the mysteries related to the quantitative and qualitative aspects of the human host response. This review will provide a focused overview of new concepts and developments in the field of vaccine biomarkers including (i) vaccine‐dependent signatures predicting subject response and safety, (ii) predicting therapeutic vaccine efficacy in chronic diseases, (iii) exploring the genetic make‐up of the host that may modulate subject‐specific adverse events or affect the quality of immune responses, and (iv) the topic of volunteer stratification as a result of biomarker screening (e.g. for therapeutic vaccines but also potentially for preventive vaccines) or as a reflection of an effort to compare select groups (e.g. vaccinated subjects versus patients recovering from infection) to enable the discovery of clinically relevant biomarkers for preventive vaccines. PMID:21895991

  20. Translational Bioinformatics for Diagnostic and Prognostic Prediction of Prostate Cancer in the Next-Generation Sequencing Era

    Directory of Open Access Journals (Sweden)

    Jiajia Chen

    2013-01-01

    Full Text Available The discovery of prostate cancer biomarkers has been boosted by the advent of next-generation sequencing (NGS technologies. Nevertheless, many challenges still exist in exploiting the flood of sequence data and translating them into routine diagnostics and prognosis of prostate cancer. Here we review the recent developments in prostate cancer biomarkers by high throughput sequencing technologies. We highlight some fundamental issues of translational bioinformatics and the potential use of cloud computing in NGS data processing for the improvement of prostate cancer treatment.

  1. Multiple Sclerosis Cerebrospinal Fluid Biomarkers

    Directory of Open Access Journals (Sweden)

    Gavin Giovannoni

    2006-01-01

    Full Text Available Cerebrospinal fluid (CSF is the body fluid closest to the pathology of multiple sclerosis (MS. For many candidate biomarkers CSF is the only fluid that can be investigated. Several factors need to be standardized when sampling CSF for biomarker research: time/volume of CSF collection, sample processing/storage, and the temporal relationship of sampling to clinical or MRI markers of disease activity. Assays used for biomarker detection must be validated so as to optimize the power of the studies. A formal method for establishing whether or not a particular biomarker can be used as a surrogate end-point needs to be adopted. This process is similar to that used in clinical trials, where the reporting of studies has to be done in a standardized way with sufficient detail to permit a critical review of the study and to enable others to reproduce the study design. A commitment must be made to report negative studies so as to prevent publication bias. Pre-defined consensus criteria need to be developed for MS-related prognostic biomarkers. Currently no candidate biomarker is suitable as a surrogate end-point. Bulk biomarkers of the neurodegenerative process such as glial fibrillary acidic protein (GFAP and neurofilaments (NF have advantages over intermittent inflammatory markers.

  2. Biomarkers for Detecting Mitochondrial Disorders

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2018-01-01

    Full Text Available (1 Objectives: Mitochondrial disorders (MIDs are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and late stages. This is why there is a need to provide biomarkers, which can be easily obtained in the case of suspecting a MID to initiate the further diagnostic work-up. (2 Methods: Literature review. (3 Results: Biomarkers for diagnostic purposes are used to confirm a suspected diagnosis and to facilitate and speed up the diagnostic work-up. For diagnosing MIDs, a number of dry and wet biomarkers have been proposed. Dry biomarkers for MIDs include the history and clinical neurological exam and structural and functional imaging studies of the brain, muscle, or myocardium by ultrasound, computed tomography (CT, magnetic resonance imaging (MRI, MR-spectroscopy (MRS, positron emission tomography (PET, or functional MRI. Wet biomarkers from blood, urine, saliva, or cerebrospinal fluid (CSF for diagnosing MIDs include lactate, creatine-kinase, pyruvate, organic acids, amino acids, carnitines, oxidative stress markers, and circulating cytokines. The role of microRNAs, cutaneous respirometry, biopsy, exercise tests, and small molecule reporters as possible biomarkers is unsolved. (4 Conclusions: The disadvantages of most putative biomarkers for MIDs are that they hardly meet the criteria for being acceptable as a biomarker (missing longitudinal studies, not validated, not easily feasible, not cheap, not ubiquitously available and that not all MIDs manifest in the brain, muscle, or myocardium. There is currently a lack of validated biomarkers for diagnosing MIDs.

  3. Translating Fashion into Danish

    DEFF Research Database (Denmark)

    Riegels Melchior, Marie; Skov, Lise; Csaba, Fabian

    2011-01-01

    emanate from Denmark and secure growth, jobs and exports even outside the fashion business has taken hold among policymakers, and compelled the government to embrace fashion as a national project. In investigating the emergence and rising stature of Danish fashion, particular at home, we first establish...... a theoretical frame for understanding the cultural economic policy and the motives, principles and strategies behind it. Then – drawing inspiration from Michel Callon’s “sociology of translation” with its moments of translation: problematization, interessement, enrolment and mobilization – we identify...... the actors and analyze their strategic roles and interrelationship through various phases of the development of Danish fashion. Callon’s actor network theory (ANT) is based on the principle of “generalized symmetry” – originally using a single repertoire to analyze both society and nature. We adapt...

  4. Found in translation

    DEFF Research Database (Denmark)

    Tietjen, Anne

    2018-01-01

    activities and uses, and people’s ideas and desires for future development can be a pertinent starting point. Furthermore, a clearly defined programming phase where design problems are formulated by different representational media and collectively assessed by students and teachers proved helpful...... analysis. Second, it presents the applied educational procedure, with a focus on the decisive step from inventory to intervention which is the formulation of a design problem. The teaching experiment shows that onsite studies of spatial controversies in the form of recent physical changes, emerging new...... for the students. Overall, the produced design work and the student evaluations show that translation offers an operational framework for teaching a creative approach to site analysis....

  5. Holography without translational symmetry

    CERN Document Server

    Vegh, David

    2013-01-01

    We propose massive gravity as a holographic framework for describing a class of strongly interacting quantum field theories with broken translational symmetry. Bulk gravitons are assumed to have a Lorentz-breaking mass term as a substitute for spatial inhomogeneities. This breaks momentum-conservation in the boundary field theory. At finite chemical potential, the gravity duals are charged black holes in asymptotically anti-de Sitter spacetime. The conductivity in these systems generally exhibits a Drude peak that approaches a delta function in the massless gravity limit. Furthermore, the optical conductivity shows an emergent scaling law: $|\\sigma(\\omega)| \\approx {A \\over \\omega^{\\alpha}} + B$. This result is consistent with that found earlier by Horowitz, Santos, and Tong who introduced an explicit inhomogeneous lattice into the system.

  6. Animal Models for Tuberculosis in Translational and Precision Medicine

    Directory of Open Access Journals (Sweden)

    Lingjun Zhan

    2017-05-01

    Full Text Available Tuberculosis (TB is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models.

  7. Proteomic analysis of tissue samples in translational breast cancer research

    DEFF Research Database (Denmark)

    Gromov, Pavel; Moreira, José; Gromova, Irina

    2014-01-01

    In the last decade, many proteomic technologies have been applied, with varying success, to the study of tissue samples of breast carcinoma for protein expression profiling in order to discover protein biomarkers/signatures suitable for: characterization and subtyping of tumors; early diagnosis...... the translation of basic discoveries into the daily breast cancer clinical practice. In particular, we address major issues in experimental design by reviewing the strengths and weaknesses of current proteomic strategies in the context of the analysis of human breast tissue specimens....

  8. THE DEVELOPMENT OF SCREEN TRANSLATION

    OpenAIRE

    Sang Ayu Isnu Maharani

    2014-01-01

    Screen translations involve oral translation known as dubbing and revoicing. Re-voicing consists of lip-sync dubbing, free commentary, narration and voice over. The written version is called subtitle. Dubbing and subtitling are two preferred mode used in the screen translation even though various numbers of current options are available nowadays. Dubbing commenced to be used in larger countries in Europe meanwhile smaller countries apply subtitling because it is more...

  9. Transferring communicative clues in translation

    OpenAIRE

    Navarro Errasti, María Pilar

    2001-01-01

    In this essay I make use of the category communicative clue, as defined by Gutt (1991/2000), to explain certain differences between an original work and its various translations. Communicative clues are very useful analytical devices that show nuances of meaning and style. In the source texts, they sometimes go unnoticed. But when a translation is done the translator may come across these features and must desirably transfer them. Very frequently, however, they are ignored. Here a particular ...

  10. Strategy Of Translating Gadget Brochure

    Directory of Open Access Journals (Sweden)

    Deny Kusuma

    2015-10-01

    Full Text Available The title of this writing is strategy of translating gadget brochure. There were two problems discussed in this thesis, namely (1 terms found in the gadget manual book and its equivalence in Indonesia, (2 strategies applied in translating gadget brochure. Based on the analysis result, it was found that the terms and its equivalent words found in the gadget brochure were classified based on: 1 simple words or compound words and terminology forming phrase. 2 words category found are: noun and verb. The recommended pattern to determine the equivalent word was pure borrowing strategy, not adaptation borrowing strategy. The adaptation borrowing in this context was related to the spellings, the pronunciation or sound adaptation in the TL rather than adaptation for the cultural substitutes that conceptually mismatches with the standardized terminology in the SL. In addition, the result of the analysis that there were seven strategies found in gadget brochure, they were translation by more general word (Superordinate, translation by a more neutral/expressive word, translation by cultural substitution, translation by using loan word or loan word plus explanation, translation by paraphrase using related word, translation by omission and translation by illustration.

  11. Specialised Translation Dictionaries for Learners

    DEFF Research Database (Denmark)

    Nielsen, Sandro

    2010-01-01

    Specialised translation dictionaries for learners are reference tools that can help users with domain discourse in a foreign language in connection with translation. The most common type is the business dictionary covering several more or less related subject fields. However, business dictionaries...... the needs of learners, it is proposed that specialised translation dictionaries should be designed as augmented reference tools. It is argued that electronic and printed dictionaries should include sections or CD-ROMs with syntactic, translation etc. data as well as exercises and illustrative documents...

  12. Cocktail effects on biomarker responses in fish

    Energy Technology Data Exchange (ETDEWEB)

    Celander, Malin C., E-mail: malin.celander@zool.gu.se [University of Gothenburg, Department of Zoology, Box 463, SE-405 30 Gothenburg (Sweden)

    2011-10-15

    One of today's greatest challenges in environmental toxicology is to understand effects of mixture toxicity, commonly referred to as cocktail effects, in humans and in wildlife. Biomarker responses in fish are routinely used to assess exposure of anthropogenic chemicals in the aquatic environment. However, little is known about how cocktail effects affect these biomarker responses. For this reason, there is an obvious risk for misinterpretation of biomarker-data and this can have profound negative effects on stakeholder's decisions and actions, as well as on legislations and remediation-plans initiated in order to reduce exposure to certain chemicals. Besides, chemical safety-levels are traditionally based on experiences from lab-studies with single chemicals, which is unfortunate as a chemical can be more toxic when it is mixed with other chemicals, because of the cocktail effect. This review focuses on pharmacokinetic interactions between different classes of pollutants on detoxification mechanisms and how that affects two commonly used biomarkers in the aquatic environment: (1) induction of cytochrome P450 1A (CYP1A) that is mediated via activation of the arylhydrocarbon receptor (AhR), used to assess exposure to aromatic hydrocarbons; (2) induction of vitellogenin (VTG) that is mediated via activation of the estrogen receptor (ER), used to assess exposure to estrogenic chemicals. These responses can be either directly or indirectly affected by the presence of other classes of pollutants as a result of cocktail effects. For example, chemicals that inhibit the function of key metabolic enzymes and transporter pumps that are involved in elimination of AhR- and ER agonists, can result in bioaccumulation of aromatic hydrocarbons and estrogenic chemicals resulting in increased biomarker responses. This cocktail effect can lead to overestimation of the actual exposure pressure. On the contrary, induction of expression of key metabolic enzymes and transporter

  13. Onomastics and Translation: The Case of Igbo→English Translation ...

    African Journals Online (AJOL)

    The qualitative research method will be used to translate, analyze and explain the data from the anthroponomical, semiotic and linguistic perspectives to show that contrary to the view held in some Western circles that names are obscure and may consist of words that can hardly be interpreted or translated, they, as symbols ...

  14. The Translation and the Translator of the Peshitta of Hosea

    Science.gov (United States)

    Tully, Eric J.

    2012-01-01

    This comprehensive examination of the Syriac Peshitta of Hosea (P-Hosea) is the first study of the Peshitta conducted via insights and methods from the discipline of Translation Studies. It uses in particular Andrew Chesterman's Causal Model and Gideon Toury's descriptive approach. Every translator leaves residue of his or her…

  15. The wise translator: reflecting on judgement in translator education ...

    African Journals Online (AJOL)

    The question of how one goes about teaching students to be translators is a central area of concern for translation teachers. As a reflective practitioner, I have a hunch about how to solve my problem. This paper is therefore in itself part of a reflective practicum, part of my reflection-in-action. I am in the process of restructuring ...

  16. Image Biomarkers and Precision Medicine: need for validation

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  17. A Study of Translation Institutional Ethics

    Institute of Scientific and Technical Information of China (English)

    LuoXianfeng; ZhouJin

    2017-01-01

    Traditional translation ethics characterized by translators' ethics cannot provide a strong moral support to the translation practice,or guarantee the moral requirement towards translation activities in the social transformation caused by the market economy,because it does not have the power of punishment.Translation institutional ethics,however,a new form of translation ethics,integrates the translation ethic norm,translation regulations and relative laws together.As an inevitable outcome in the new era,it can escort the orderly and healthy translation activities.Its purpose is to strengthen the translators' moral consciousness,to sublimate their moral notions and to transfer from heteronomy to autonomy.

  18. Translation Memory and Computer Assisted Translation Tool for Medieval Texts

    Directory of Open Access Journals (Sweden)

    Törcsvári Attila

    2013-05-01

    Full Text Available Translation memories (TMs, as part of Computer Assisted Translation (CAT tools, support translators reusing portions of formerly translated text. Fencing books are good candidates for using TMs due to the high number of repeated terms. Medieval texts suffer a number of drawbacks that make hard even “simple” rewording to the modern version of the same language. The analyzed difficulties are: lack of systematic spelling, unusual word orders and typos in the original. A hypothesis is made and verified that even simple modernization increases legibility and it is feasible, also it is worthwhile to apply translation memories due to the numerous and even extremely long repeated terms. Therefore, methods and algorithms are presented 1. for automated transcription of medieval texts (when a limited training set is available, and 2. collection of repeated patterns. The efficiency of the algorithms is analyzed for recall and precision.

  19. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An

    2015-12-01

    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.

  20. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille

    2009-01-01

    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....

  1. A guide to introducing burnup credit, preliminary version (English translation)

    International Nuclear Information System (INIS)

    Okuno, Hiroshi; Suyama, Kenya; Ryufuku, Susumu

    2017-06-01

    There is an ongoing discussion on the application of burnup credit to the criticality safety controls of facilities that treat spent fuels. With regard to such application of burnup credit in Japan, this document summarizes the current technical status of the prediction of the isotopic composition and criticality of spent fuels, as well as safety evaluation concerns and the current status of legal affairs. This report is an English translation of A Guide to Introducing Burnup Credit, Preliminary Version, originally published in Japanese as JAERI-Tech 2001-055 by the Nuclear Fuel Cycle Facility Safety Research Committee. (author)

  2. Breath biomarkers in toxicology.

    Science.gov (United States)

    Pleil, Joachim D

    2016-11-01

    Exhaled breath has joined blood and urine as a valuable resource for sampling and analyzing biomarkers in human media for assessing exposure, uptake metabolism, and elimination of toxic chemicals. This article focuses current use of exhaled gas, aerosols, and vapor in human breath, the methods for collection, and ultimately the use of the resulting data. Some advantages of breath are the noninvasive and self-administered nature of collection, the essentially inexhaustible supply, and that breath sampling does not produce potentially infectious waste such as needles, wipes, bandages, and glassware. In contrast to blood and urine, breath samples can be collected on demand in rapid succession and so allow toxicokinetic observations of uptake and elimination in any time frame. Furthermore, new technologies now allow capturing condensed breath vapor directly, or just the aerosol fraction alone, to gain access to inorganic species, lung pH, proteins and protein fragments, cellular DNA, and whole microorganisms from the pulmonary microbiome. Future applications are discussed, especially the use of isotopically labeled probes, non-targeted (discovery) analysis, cellular level toxicity testing, and ultimately assessing "crowd breath" of groups of people and the relation to dose of airborne and other environmental chemicals at the population level.

  3. Analysis of biomarker data a practical guide

    CERN Document Server

    Looney, Stephen W

    2015-01-01

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

  4. Reconceptualising translation in agricultural innovation

    NARCIS (Netherlands)

    Ingram, Julie; Dwyer, Janet; Gaskell, Peter; Mills, Jane; Wolf, de Pieter

    2018-01-01

    Scientific research continues to play a significant role in meeting the multiple innovation challenges in agriculture. If this role is to be fulfilled, provision needs to be made for effective translation of research outputs, where translation is understood to be the process whereby science becomes

  5. PATRAN-STAGS translator (PATSTAGS)

    Science.gov (United States)

    Otte, Neil

    1990-01-01

    A a computer program used to translate PATRAN finite element model data into Structural Analysis of General Shells (STAGS) input data is presented. The program supports translation of nodal, nodal constraints, element, force, and pressure data. The subroutine UPRESS required for the readings of live pressure data into STAGS is also presented.

  6. Translation research: from accurate diagnosis to appropriate treatment

    Directory of Open Access Journals (Sweden)

    Pass Harvey I

    2004-10-01

    Full Text Available Abstract This review article focuses on the various aspects of translational research, where research on human subjects can ultimately enhance the diagnosis and treatment of future patients. While we will use specific examples relating to the asbestos related cancer mesothelioma, it should be stressed that the general approach outlined throughout this review is readily applicable to other diseases with an underlying molecular basis. Through the integration of molecular-based technologies, systematic tissue procurement and medical informatics, we now have the ability to identify clinically applicable "genotype"-"phenotype" associations across cohorts of patients that can rapidly be translated into useful diagnostic and treatment strategies. This review will touch on the various steps in the translational pipeline, and highlight some of the most essential elements as well as possible roadblocks that can impact success of the program. Critical issues with regard to Institutional Review Board (IRB and Health Insurance Portability and Accountability Act (HIPAA compliance, data standardization, sample procurement, quality control (QC, quality assurance (QA, data analysis, preclinical models and clinical trials are addressed. The various facets of the translational pipeline have been incorporated into a fully integrated computational system, appropriately named Dx2Tx. This system readily allows for the identification of new diagnostic tests, the discovery of biomarkers and drugable targets, and prediction of optimal treatments based upon the underlying molecular basis of the disease.

  7. Knowledge Translation in Audiology

    Science.gov (United States)

    Kothari, Anita; Bagatto, Marlene P.; Seewald, Richard; Miller, Linda T.; Scollie, Susan D.

    2011-01-01

    The impetus for evidence-based practice (EBP) has grown out of widespread concern with the quality, effectiveness (including cost-effectiveness), and efficiency of medical care received by the public. Although initially focused on medicine, EBP principles have been adopted by many of the health care professions and are often represented in practice through the development and use of clinical practice guidelines (CPGs). Audiology has been working on incorporating EBP principles into its mandate for professional practice since the mid-1990s. Despite widespread efforts to implement EBP and guidelines into audiology practice, gaps still exist between the best evidence based on research and what is being done in clinical practice. A collaborative dynamic and iterative integrated knowledge translation (KT) framework rather than a researcher-driven hierarchical approach to EBP and the development of CPGs has been shown to reduce the knowledge-to-clinical action gaps. This article provides a brief overview of EBP and CPGs, including a discussion of the barriers to implementing CPGs into clinical practice. It then offers a discussion of how an integrated KT process combined with a community of practice (CoP) might facilitate the development and dissemination of evidence for clinical audiology practice. Finally, a project that uses the knowledge-to-action (KTA) framework for the development of outcome measures in pediatric audiology is introduced. PMID:22194314

  8. Revising and editing for translators

    CERN Document Server

    Mossop, Brian

    2014-01-01

    Revising and Editing for Translators provides guidance and learning materials for translation students learning to edit texts written by others, and professional translators wishing to improve their self-revision ability or learning to revise the work of others. Editing is understood as making corrections and improvements to texts, with particular attention to tailoring them to the given readership. Revising is this same task applied to draft translations. The linguistic work of editors and revisers is related to the professional situations in which they work. Mossop offers in-depth coverage of a wide range of topics, including copyediting, style editing, structural editing, checking for consistency, revising procedures and principles, and translation quality assessment. This third edition provides extended coverage of computer aids for revisers, and of the different degrees of revision suited to different texts. The inclusion of suggested activities and exercises, numerous real-world examples, a proposed gra...

  9. Biomedical informatics and translational medicine

    Directory of Open Access Journals (Sweden)

    Sarkar Indra

    2010-02-01

    Full Text Available Abstract Biomedical informatics involves a core set of methodologies that can provide a foundation for crossing the "translational barriers" associated with translational medicine. To this end, the fundamental aspects of biomedical informatics (e.g., bioinformatics, imaging informatics, clinical informatics, and public health informatics may be essential in helping improve the ability to bring basic research findings to the bedside, evaluate the efficacy of interventions across communities, and enable the assessment of the eventual impact of translational medicine innovations on health policies. Here, a brief description is provided for a selection of key biomedical informatics topics (Decision Support, Natural Language Processing, Standards, Information Retrieval, and Electronic Health Records and their relevance to translational medicine. Based on contributions and advancements in each of these topic areas, the article proposes that biomedical informatics practitioners ("biomedical informaticians" can be essential members of translational medicine teams.

  10. Translating Measures of Biological Aging to Test Effectiveness of Geroprotective Interventions: What Can We Learn from Research on Telomeres?

    Directory of Open Access Journals (Sweden)

    Waylon J. Hastings

    2017-11-01

    Full Text Available Intervention studies in animals suggest molecular changes underlying age-related disease and disability can be slowed or reversed. To speed translation of these so-called “geroprotective” therapies to prevent age-related disease and disability in humans, biomarkers are needed that can track changes in the rate of human aging over the course of intervention trials. Algorithm methods that measure biological processes of aging from combinations of DNA methylation marks or clinical biomarkers show promise. To identify next steps for establishing utility of these algorithm-based measures of biological aging for geroprotector trials, we considered the history a candidate biomarker of aging that has received substantial research attention, telomere length. Although telomere length possesses compelling biology to recommend it as a biomarker of aging, mixed research findings have impeded clinical and epidemiologic translation. Strengths of telomeres that should be established for algorithm biomarkers of aging are correlation with chronological age across the lifespan, prediction of disease, disability, and early death, and responsiveness to risk and protective exposures. Key challenges in telomere research that algorithm biomarkers of aging must address are measurement precision and reliability, establishing links between longitudinal rates of change across repeated measurements and aging outcomes, and clarity over whether the biomarker is a causal mechanism of aging. These strengths and challenges suggest a research agenda to advance translation of algorithm-based aging biomarkers: establish validity in young-adult and midlife individuals; test responsiveness to exposures that shorten or extend healthy lifespan; and conduct repeated-measures longitudinal studies to test differential rates of change.

  11. TRANSLATING BLACKNESS: A CHALLENGE TO TRANSLATION STUDIES IN CONTEMPORANEITY

    Directory of Open Access Journals (Sweden)

    Maria Aparecida Andrade Salgueiro

    2014-07-01

    Full Text Available The present article presents aspects of a work in progress about both African-American and Afro-Brazilian Literatures as well as Translation Studies. As it makes observations about how blackness has been translated in different contexts and geographical spaces, it calls the reader’s attention to power relations, processes of colonial and post-colonial identity construction, the rising of literary canons, cultural hegemony and globalization, demystifying spaces and showing translation as an activity that does not take place in a neutral space, but, for sure, inside social and political concrete situations.

  12. Knowledge translation of research findings

    Directory of Open Access Journals (Sweden)

    Grimshaw Jeremy M

    2012-05-01

    Full Text Available Abstract Background One of the most consistent findings from clinical and health services research is the failure to translate research into practice and policy. As a result of these evidence-practice and policy gaps, patients fail to benefit optimally from advances in healthcare and are exposed to unnecessary risks of iatrogenic harms, and healthcare systems are exposed to unnecessary expenditure resulting in significant opportunity costs. Over the last decade, there has been increasing international policy and research attention on how to reduce the evidence-practice and policy gap. In this paper, we summarise the current concepts and evidence to guide knowledge translation activities, defined as T2 research (the translation of new clinical knowledge into improved health. We structure the article around five key questions: what should be transferred; to whom should research knowledge be transferred; by whom should research knowledge be transferred; how should research knowledge be transferred; and, with what effect should research knowledge be transferred? Discussion We suggest that the basic unit of knowledge translation should usually be up-to-date systematic reviews or other syntheses of research findings. Knowledge translators need to identify the key messages for different target audiences and to fashion these in language and knowledge translation products that are easily assimilated by different audiences. The relative importance of knowledge translation to different target audiences will vary by the type of research and appropriate endpoints of knowledge translation may vary across different stakeholder groups. There are a large number of planned knowledge translation models, derived from different disciplinary, contextual (i.e., setting, and target audience viewpoints. Most of these suggest that planned knowledge translation for healthcare professionals and consumers is more likely to be successful if the choice of knowledge

  13. Knowledge translation of research findings.

    Science.gov (United States)

    Grimshaw, Jeremy M; Eccles, Martin P; Lavis, John N; Hill, Sophie J; Squires, Janet E

    2012-05-31

    One of the most consistent findings from clinical and health services research is the failure to translate research into practice and policy. As a result of these evidence-practice and policy gaps, patients fail to benefit optimally from advances in healthcare and are exposed to unnecessary risks of iatrogenic harms, and healthcare systems are exposed to unnecessary expenditure resulting in significant opportunity costs. Over the last decade, there has been increasing international policy and research attention on how to reduce the evidence-practice and policy gap. In this paper, we summarise the current concepts and evidence to guide knowledge translation activities, defined as T2 research (the translation of new clinical knowledge into improved health). We structure the article around five key questions: what should be transferred; to whom should research knowledge be transferred; by whom should research knowledge be transferred; how should research knowledge be transferred; and, with what effect should research knowledge be transferred? We suggest that the basic unit of knowledge translation should usually be up-to-date systematic reviews or other syntheses of research findings. Knowledge translators need to identify the key messages for different target audiences and to fashion these in language and knowledge translation products that are easily assimilated by different audiences. The relative importance of knowledge translation to different target audiences will vary by the type of research and appropriate endpoints of knowledge translation may vary across different stakeholder groups. There are a large number of planned knowledge translation models, derived from different disciplinary, contextual (i.e., setting), and target audience viewpoints. Most of these suggest that planned knowledge translation for healthcare professionals and consumers is more likely to be successful if the choice of knowledge translation strategy is informed by an assessment of the

  14. Amyloid Biomarkers in Conformational Diseases at Face Value: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Maria Fernanda Avila-Vazquez

    2017-12-01

    Full Text Available Conformational diseases represent a new aspect of proteomic medicine where diagnostic and therapeutic paradigms are evolving. In this context, the early biomarkers for target cell failure (neurons, β-cells, etc. represent a challenge to translational medicine and play a multidimensional role as biomarkers and potential therapeutic targets. This systematic review, which follows the PICO and Prisma methods, analyses this new-fangled multidimensionality, its strengths and limitations, and presents the future possibilities it opens up. The nuclear diagnosis methods are immunoassays: ELISA, immunodot, western blot, etc., while the therapeutic approach is focused on pharmaco- and molecular chaperones.

  15. The "Pedagogue as Translator" in the Classroom

    Science.gov (United States)

    Dobson, Stephen

    2012-01-01

    Translation theory has faced criticism from professional translators for adopting an ivory tower stance to the "real world" challenges of translation. This article argues that a case can be made for considering the challenges of translation as it takes place in the school classroom. In support of such an argument the pedagogue as translator is…

  16. A Protocol of Japanese-English Translation

    OpenAIRE

    三浦, 勲夫; MIURA, Isao

    1999-01-01

    Every year I translate Japanes enewspaper articles into English and publish them in book form containing 12 or more translations. In translating there are regular procedures I go through:1)initial translation done by me and 2) corrected translation done through discussion between a native English speaker and me.

  17. Translating Romans: some persistent headaches

    Directory of Open Access Journals (Sweden)

    A.B. du Toit

    2010-07-01

    Full Text Available Translating Romans: some persistent headaches Gone are the days when it was axiomatic that expertise in biblical languages automatically qualified one as a Bible translator. In 1949, Ronald Knox, who for nine years conscientiously struggled with translating the Bible for his generation, published a booklet under the title The trials of a translator. At that stage Bible translation as the subject of scientific study was still in its infancy. Since then, research into the intricacies of communicating the biblical message in an authentic but understandable manner, has made significant progress (cf. Roberts, 2009. However, the frustrations of Bible translators, first of all to really understand what the biblical authors wanted to convey to their original addressees, and then to commu-nicate that message to their own targeted readers in a meaningful way, have not disappeared. In fact, the challenge to meet the vary-ing requirements of the multiple kinds of translation that are present-ly in vogue, has only increased.

  18. Harold Pinter in Slovene Translation

    Directory of Open Access Journals (Sweden)

    Darja Hribar

    2004-12-01

    Full Text Available This article examines the translation of Harold Pinter’s most notable stylistic peculiarities into Slovene, illustrating its main points with examples taken from his play The Homecoming. The findings demonstrate above all a marked degree of non-observance of the special verbal pattern (special cohesion of the originals, a failure to convey Pinter’s special configuration of meaning (special coherence, and a disregard for internal unifying coincidences. It argues that the Slovene translations of Pinter rely mostly on traditional theories of meaning and of language norms, thus preventing the reproduction of those emotional and psychological actions of Pinter’s characters which are usually not expressed by means of the rhetorical, informative elements of his dialogue, but by its form and sonority, i. e. the length, strength, and level of articulation of verbal expression. This blurs Pinter’s famous logic of emotion, narrows the proverbial openness and conceptual uncertainty of his plays, and limits their potential vitality in translation. Taking into account current drama and theatre translation practices in Slovenia, i.e. the rarity of published drama translation and the dependence on a translated performance text for subsequent theatrical productions, the article argues that in such cases the drama translation should be retrospective, i.e. aiming at a maximum reconstruction of all relevant linguistic, stylistic, and textual properties of the original, leaving expressly subjective interventions in the text to the theatre practitioners.

  19. Strategies for Translating Vocative Texts

    Directory of Open Access Journals (Sweden)

    Olga COJOCARU

    2014-12-01

    Full Text Available The paper deals with the linguistic and cultural elements of vocative texts and the techniques used in translating them by giving some examples of texts that are typically vocative (i.e. advertisements and instructions for use. Semantic and communicative strategies are popular in translation studies and each of them has its own advantages and disadvantages in translating vocative texts. The advantage of semantic translation is that it takes more account of the aesthetic value of the SL text, while communicative translation attempts to render the exact contextual meaning of the original text in such a way that both content and language are readily acceptable and comprehensible to the readership. Focus is laid on the strategies used in translating vocative texts, strategies that highlight and introduce a cultural context to the target audience, in order to achieve their overall purpose, that is to sell or persuade the reader to behave in a certain way. Thus, in order to do that, a number of advertisements from the field of cosmetics industry and electronic gadgets were selected for analysis. The aim is to gather insights into vocative text translation and to create new perspectives on this field of research, now considered a process of innovation and diversion, especially in areas as important as economy and marketing.

  20. A proposed panel of biomarkers of healthy ageing.

    Science.gov (United States)

    Lara, Jose; Cooper, Rachel; Nissan, Jack; Ginty, Annie T; Khaw, Kay-Tee; Deary, Ian J; Lord, Janet M; Kuh, Diana; Mathers, John C

    2015-09-15

    There is no criterion reference for assessing healthy ageing and this creates difficulties when conducting and comparing research on ageing across studies. A cardinal feature of ageing is loss of function which translates into wide-ranging consequences for the individual and for family, carers and society. We undertook comprehensive reviews of the literature searching for biomarkers of ageing on five ageing-related domains including physical capability and cognitive, physiological and musculoskeletal, endocrine and immune functions. Where available, we used existing systematic reviews, meta-analyses and other authoritative reports such as the recently launched NIH Toolbox for assessment of neurological and behavioural function, which includes test batteries for cognitive and motor function (the latter described here as physical capability). We invited international experts to comment on our draft recommendations. In addition, we hosted an experts workshop in Newcastle, UK, on 22-23 October 2012, aiming to help capture the state-of-the-art in this complex area and to provide an opportunity for the wider ageing research community to critique the proposed panel of biomarkers. Here we have identified important biomarkers of healthy ageing classified as subdomains of the main areas proposed. Cardiovascular and lung function, glucose metabolism and musculoskeletal function are key subdomains of physiological function. Strength, locomotion, balance and dexterity are key physical capability subdomains. Memory, processing speed and executive function emerged as key subdomains of cognitive function. Markers of the HPA-axis, sex hormones and growth hormones were important biomarkers of endocrine function. Finally, inflammatory factors were identified as important biomarkers of immune function. We present recommendations for a panel of biomarkers that address these major areas of function which decline during ageing. This biomarker panel may have utility in epidemiological

  1. Translating the covenant: The behavior analyst as ambassador and translator.

    Science.gov (United States)

    Foxx, R M

    1996-01-01

    Behavior analysts should be sensitive to how others react to and interpret our language because it is inextricably related to our image. Our use of conceptual revision, with such terms as punishment, has created communicative confusion and hostility on the part of general and professional audiences we have attempted to influence. We must, therefore, adopt the role of ambassador and translator in the nonbehavioral world. A number of recommendations are offered for promoting, translating, and disseminating behavior analysis.

  2. THE DEVELOPMENT OF SCREEN TRANSLATION

    Directory of Open Access Journals (Sweden)

    Sang Ayu Isnu Maharani

    2014-05-01

    Full Text Available Screen translations involve oral translation known as dubbing and revoicing. Re-voicing consists of lip-sync dubbing, free commentary, narration and voice over. The written version is called subtitle. Dubbing and subtitling are two preferred mode used in the screen translation even though various numbers of current options are available nowadays. Dubbing commenced to be used in larger countries in Europe meanwhile smaller countries apply subtitling because it is more economical than dubbing. In Indonesia, the use of dubbing as well as subtitle are found.

  3. Translation and spaces of reading

    Directory of Open Access Journals (Sweden)

    Clive Scott

    2014-01-01

    Full Text Available The author discusses relations between the original and translation in terms of imaginary spaces. Target text is understood here as one of the possible images of the source text, from the perspective which could not be accessible to the original. In accordance with the concept presented here, artistic translation can be not so much reconstructed, as conceptually constructed, in the manner of a cubist object. Acts of creative reading are commented on by the author with examples of his own experimental translations from contemporary French poetry.

  4. Eye-movements During Translation

    DEFF Research Database (Denmark)

    Balling, Laura Winther

    2013-01-01

    texts as well as both eye-tracking and keylogging data. Based on this database, I present a large-scale analysis of gaze on the source text based on 91 translators' translations of six different texts from English into four different target languages. I use mixed-effects modelling to compare from......, and variables indexing the alignment between the source and target texts. The results are related to current models of translation processes and reading and compared to a parallel analysis of production time....

  5. Biomarkers in acute heart failure.

    Science.gov (United States)

    Mallick, Aditi; Januzzi, James L

    2015-06-01

    The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  6. Auto Safety

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Auto Safety KidsHealth / For Parents / Auto Safety What's in this ... by teaching some basic rules. Importance of Child Safety Seats Using a child safety seat (car seat) ...

  7. The Translator's Turn: in the Cultural Turn

    Institute of Scientific and Technical Information of China (English)

    徐玮玮

    2003-01-01

    @@ Introduction: Douglas Robinson rose to the defense of the " atheoretical" American literary translator in The Translator's Turn (1991). Here, I borrowed the title from him, but I will write my paper in the thought of the translator's role in translating. In his book, Robinson argued that the literary translator embodies an integration of feeling and thought, of intuition and systematization. In analyzing the " turn" that the translator take from the source text to the target text, Robinson offered a " dialogical" model, that is the translator's dialogical engagement with the source language and with the ethic of the target language. Robinson allows for the translator to intervene, subvert, divert, even entertain, emphasizing the creative aspect of literary translation. The translation linguists, scientists, and philosophers have had their chance at translation theory; now it is time, he argued, for the literary translators to have their " turn".

  8. Circulating microRNAs as Potential Biomarkers of Infectious Disease

    Science.gov (United States)

    Correia, Carolina N.; Nalpas, Nicolas C.; McLoughlin, Kirsten E.; Browne, John A.; Gordon, Stephen V.; MacHugh, David E.; Shaughnessy, Ronan G.

    2017-01-01

    microRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules that regulate a wide range of biological processes by post-transcriptionally regulating gene expression. Thousands of these molecules have been discovered to date, and multiple miRNAs have been shown to coordinately fine-tune cellular processes key to organismal development, homeostasis, neurobiology, immunobiology, and control of infection. The fundamental regulatory role of miRNAs in a variety of biological processes suggests that differential expression of these transcripts may be exploited as a novel source of molecular biomarkers for many different disease pathologies or abnormalities. This has been emphasized by the recent discovery of remarkably stable miRNAs in mammalian biofluids, which may originate from intracellular processes elsewhere in the body. The potential of circulating miRNAs as biomarkers of disease has mainly been demonstrated for various types of cancer. More recently, however, attention has focused on the use of circulating miRNAs as diagnostic/prognostic biomarkers of infectious disease; for example, human tuberculosis caused by infection with Mycobacterium tuberculosis, sepsis caused by multiple infectious agents, and viral hepatitis. Here, we review these developments and discuss prospects and challenges for translating circulating miRNA into novel diagnostics for infectious disease. PMID:28261201

  9. Immunohistochemistry of colorectal cancer biomarker phosphorylation requires controlled tissue fixation.

    Directory of Open Access Journals (Sweden)

    Abbey P Theiss

    Full Text Available Phosphorylated signaling molecules are biomarkers of cancer pathophysiology and resistance to therapy, but because phosphoprotein analytes are often labile, poorly controlled clinical laboratory practices could prevent translation of research findings in this area from the bench to the bedside. We therefore compared multiple biomarker and phosphoprotein immunohistochemistry (IHC results in 23 clinical colorectal carcinoma samples after either a novel, rapid tissue fixation protocol or a standard tissue fixation protocol employed by clinical laboratories, and we also investigated the effect of a defined post-operative "cold" ischemia period on these IHC results. We found that a one-hour cold ischemia interval, allowed by ASCO/CAP guidelines for certain cancer biomarker assays, is highly deleterious to certain phosphoprotein analytes, specifically the phosphorylated epidermal growth factor receptor (pEGFR, but shorter ischemic intervals (less than 17 minutes facilitate preservation of phosphoproteins. Second, we found that a rapid 4-hour, two temperature, formalin fixation yielded superior staining in several cases with select markers (pEGFR, pBAD, pAKT compared to a standard overnight room temperature fixation protocol, despite taking less time. These findings indicate that the future research and clinical utilities of phosphoprotein IHC for assessing colorectal carcinoma pathophysiology absolutely depend upon attention to preanalytical factors and rigorously controlled tissue fixation protocols.

  10. Circulating MicroRNAs as Potential Biomarkers of Exercise Response

    Directory of Open Access Journals (Sweden)

    Mája Polakovičová

    2016-10-01

    Full Text Available Systematic physical activity increases physical fitness and exercise capacity that lead to the improvement of health status and athletic performance. Considerable effort is devoted to identifying new biomarkers capable of evaluating exercise performance capacity and progress in training, early detection of overtraining, and monitoring health-related adaptation changes. Recent advances in OMICS technologies have opened new opportunities in the detection of genetic, epigenetic and transcriptomic biomarkers. Very promising are mainly small non-coding microRNAs (miRNAs. miRNAs post-transcriptionally regulate gene expression by binding to mRNA and causing its degradation or inhibiting translation. A growing body of evidence suggests that miRNAs affect many processes and play a crucial role not only in cell differentiation, proliferation and apoptosis, but also affect extracellular matrix composition and maintaining processes of homeostasis. A number of studies have shown changes in distribution profiles of circulating miRNAs (c-miRNAs associated with various diseases and disorders as well as in samples taken under physiological conditions such as pregnancy or physical exercise. This overview aims to summarize the current knowledge related to the response of blood c-miRNAs profiles to different modes of exercise and to highlight their potential application as a novel class of biomarkers of physical performance capacity and training adaptation.

  11. Biomarkers in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bennike, Tue; Birkelund, Svend; Stensballe, Allan

    2014-01-01

    Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers...... for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment...... 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...

  12. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  13. Approaches to translational plant science

    DEFF Research Database (Denmark)

    Dresbøll, Dorte Bodin; Christensen, Brian; Thorup-Kristensen, Kristian

    2015-01-01

    is lessened. In our opinion, implementation of translational plant science is a necessity in order to solve the agricultural challenges of producing food and materials in the future. We suggest an approach to translational plant science forcing scientists to think beyond their own area and to consider higher......Translational science deals with the dilemma between basic research and the practical application of scientific results. In translational plant science, focus is on the relationship between agricultural crop production and basic science in various research fields, but primarily in the basic plant...... science. Scientific and technological developments have allowed great progress in our understanding of plant genetics and molecular physiology, with potentials for improving agricultural production. However, this development has led to a separation of the laboratory-based research from the crop production...

  14. Translating English Idioms and Collocations

    Directory of Open Access Journals (Sweden)

    Rochayah Machali

    2004-01-01

    Full Text Available Learners of English should be made aware of the nature, types, and use of English idioms. This paper disensses the nature of idioms and collocations and translation issues related to them

  15. Coordinator, Translation Services | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Coordinator, Translation Services coordinates the overall operations of the ... services in IDRC by acting as the main resource person for internal clients ... all operational issues in order to ensure good quality products delivered on time.

  16. Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers.

    Science.gov (United States)

    Wu, Hua-Hsi; Lin, Wen-chang; Tsai, Kuo-Wang

    2014-01-23

    Carcinoma of the stomach is one of the most prevalent cancer types in the world. Although the incidence of gastric cancer is declining, the outcomes of gastric cancer patients remain dismal because of the lack of effective biomarkers to detect early gastric cancer. Modern biomedical research has explored many potential gastric cancer biomarker genes by utilising serum protein antigens, oncogenic genes or gene families through improving molecular biological technologies, such as microarray, RNA-Seq and the like. Recently, the small noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the oncogenesis pathways and to serve as useful clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis, including gastric cancer. By translational suppression of target genes, miRNAs play a significant role in the gastric cancer cell physiology and tumour progression. There are potential implications of previously discovered gastric cancer molecular biomarkers and their expression modulations by respective miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour-suppressing functions in human cancers. With the surprising stability of miRNAs in tissues, serum or other body fluids, miRNAs have emerged as a new type of cancer biomarker with immeasurable clinical potential.

  17. LABORATORY BIOMARKERS FOR ANKYLOSING SPONDYLITIS

    Directory of Open Access Journals (Sweden)

    E. N. Aleksandrova

    2017-01-01

    Full Text Available Ankylosing spondylitis (AS is a chronic inflammatory disease from a group of spondyloarthritis (SpA, which is characterized by lesions of the sacroiliac joints and spine with the common involvement of entheses and peripheral joints in the pathological process. Advances in modern laboratory medicine have contributed to a substantial expansion of the range of pathogenetic, diagnostic, and prognostic biomarkers of AS. As of now, there are key pathogenetic biomarkers of AS (therapeutic targets, which include tumor necrosis factor-α (TNF-α, interleukin 17 (IL-17, and IL-23. Among the laboratory diagnostic and prognostic biomarkers, HLA-B27 and C-reactive protein are of the greatest value in clinical practice; the former for the early diagnosis of the disease and the latter for the assessment of disease activity, the risk of radiographic progression and the efficiency of therapy. Anti-CD74 antibodies are a new biomarker that has high sensitivity and specificity values in diagnosing axial SpA at an early stage. A number of laboratory biomarkers, including calprotectin, matrix metalloproteinase-3 (MMP-3, vascular endothelial growth factor, Dickkopf-1 (Dkk-1, and C-terminal telopeptide of type II collagen (CTX II do not well reflect disease activity, but may predict progressive structural changes in the spine and sacroiliac joints in AS. Blood calprotectin level monitoring allows the effective prediction of a response to therapy with TNF inhibitors and anti-IL-17А monoclonal antibodies. The prospects for the laboratory diagnosis of AS are associated with the clinical validation of candidate biomarkers during large-scale prospective cohort studies and with a search for new proteomic, transcriptomic and genomic markers, by using innovative molecular and cellular technologies.

  18. Optimising Comprehensibility in Interlingual Translation

    DEFF Research Database (Denmark)

    Nisbeth Jensen, Matilde

    2015-01-01

    The increasing demand for citizen engagement in areas traditionally belonging exclusively to experts, such as health, law and technology has given rise to the necessity of making expert knowledge available to the general public through genres such as instruction manuals for consumer goods, patien...... the functional text type of Patient Information Leaflet. Finally, the usefulness of applying the principles of Plain Language and intralingual translation for optimising comprehensibility in interlingual translation is discussed....

  19. Expanding the knowledge translation metaphor.

    Science.gov (United States)

    Engebretsen, Eivind; Sandset, Tony Joakim; Ødemark, John

    2017-03-13

    Knowledge translation (KT) is a buzzword in modern medical science. However, there has been little theoretical reflection on translation as a process of meaning production in KT. In this paper, we argue that KT will benefit from the incorporation of a more theoretical notion of translation as an entangled material, textual and cultural process. We discuss and challenge fundamental assumptions in KT, drawing on theories of translation from the human sciences. We show that the current construal of KT as separate from and secondary to the original scientific message is close to the now deeply compromised literary view of translation as the simple act of copying the original. Inspired by recent theories of translation, we claim that KT can be more adequately understood in terms of a 'double supplement' - on the one hand, KT offers new approaches to the communication of scientific knowledge to different groups in the healthcare system with the aim of supplementing a lack of knowledge among clinicians (and patients). On the other, it demonstrates that a textual and cultural supplement, namely a concern with target audiences (clinicians and patients), is inevitable in the creation of an 'autonomous' science. Hence, the division between science and its translation is unproductive and impossible to maintain. We discuss some possible implications of our suggested shift in concept by drawing on pharmaceutical interventions for the prevention of HIV as a case. We argue that such interventions are based on a supplementary and paradoxical relation to the target audiences, both presupposing and denying their existence. More sophisticated theories of translation can lay the foundation for an expanded model of KT that incorporates a more adequate and reflective description of the interdependency of scientific, cultural, textual and material practices.

  20. The Society for Translational Medicine

    DEFF Research Database (Denmark)

    Gao, Shugeng; Zhang, Zhongheng; Aragón, Javier

    2017-01-01

    The Society for Translational Medicine and The Chinese Society for Thoracic and Cardiovascular Surgery conducted a systematic review of the literature in an attempt to improve our understanding in the postoperative management of chest tubes of patients undergoing pulmonary lobectomy. Recommendati......The Society for Translational Medicine and The Chinese Society for Thoracic and Cardiovascular Surgery conducted a systematic review of the literature in an attempt to improve our understanding in the postoperative management of chest tubes of patients undergoing pulmonary lobectomy...

  1. Style and ideology in translation

    CERN Document Server

    Munday, Jeremy

    2013-01-01

    Adopting an interdisciplinary approach, this book investigates the style, or 'voice,' of English language translations of twentieth-century Latin American writing, including fiction, political speeches, and film. Existing models of stylistic analysis, supported at times by computer-assisted analysis, are developed to examine a range of works and writers, selected for their literary, cultural, and ideological importance. The style of the different translators is subjected to a close linguistic investigation within their cultural and ideological framework.

  2. Translating Linguistic Jokes for Dubbing

    Directory of Open Access Journals (Sweden)

    Elena ALEKSANDROVA

    2012-01-01

    Full Text Available This study has attempted to establish the possible ways of translating linguistic jokes whendubbing. The study is also intended to identify the most problematic cases of screen translation andthe factors which cause these problems. In order to support such an approach a corpus of 7American and British films has been compiled, including as many as 16 as their various dubbingtranslations into Russian. In the films, almost 12 instances of original linguistic jokes have beenidentified.

  3. Biomarkers in scleroderma: Current status

    Directory of Open Access Journals (Sweden)

    Latika Gupta

    2017-01-01

    Full Text Available Scleroderma is an autoimmune disease characterized by indolent obliterative vasculopathy and widespread fibrosis. The two main morphological manifestations of the disease overlap and may make it difficult to separate activity from damage. Many patients, especially those with the limited subset of the disease, have an indolent course without clear-cut inflammatory manifestations. There is a felt need for validated biomarkers, which can differentiate activity from damage, and yet be sensitive to change with therapy. Multiplex arrays of biomarkers have ushered an era of targeted or personalized medicine based on phenotypic characteristics in an individual.

  4. Developing a translational ecology workforce

    Science.gov (United States)

    Schwartz, Mark W.; Hiers, J. Kevin; Davis, Frank W.; Garfin, Gregg; Jackson, Stephen T.; Terando, Adam J.; Woodhouse, Connie A.; Morelli, Toni; Williamson, Matthew A.; Brunson, Mark W.

    2017-01-01

    We define a translational ecologist as a professional ecologist with diverse disciplinary expertise and skill sets, as well as a suitable personal disposition, who engages across social, professional, and disciplinary boundaries to partner with decision makers to achieve practical environmental solutions. Becoming a translational ecologist requires specific attention to obtaining critical non‐scientific disciplinary breadth and skills that are not typically gained through graduate‐level education. Here, we outline a need for individuals with broad training in interdisciplinary skills, use our personal experiences as a basis for assessing the types of interdisciplinary skills that would benefit potential translational ecologists, and present steps that interested ecologists may take toward becoming translational. Skills relevant to translational ecologists may be garnered through personal experiences, informal training, short courses, fellowships, and graduate programs, among others. We argue that a translational ecology workforce is needed to bridge the gap between science and natural resource decisions. Furthermore, we argue that this task is a cooperative responsibility of individuals interested in pursuing these careers, educational institutions interested in training scientists for professional roles outside of academia, and employers seeking to hire skilled workers who can foster stakeholder‐engaged decision making.

  5. Translational Repression in Malaria Sporozoites

    Science.gov (United States)

    Turque, Oliver; Tsao, Tiffany; Li, Thomas; Zhang, Min

    2016-01-01

    Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by the parasitic protozoan, Plasmodium. Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations. Here, we summarize recent advances in the translational repression of gene expression in the malaria sporozoite. In sporozoites, many mRNAs that are required for liver stage development are translationally repressed. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α) leads to a global translational repression in sporozoites. The eIF2α kinase, known as Upregulated in Infectious Sporozoite 1 (UIS1), is dominant in the sporozoite. The eIF2α phosphatase, UIS2, is translationally repressed by the Pumilio protein Puf2. This translational repression is alleviated when sporozoites are delivered into the mammalian host. PMID:28357358

  6. Translational repression in malaria sporozoites

    Directory of Open Access Journals (Sweden)

    Oliver Turque

    2016-04-01

    Full Text Available Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by the parasitic protozoan, Plasmodium. Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations. Here, we summarize recent advances in the translational repression of gene expression in the malaria sporozoite. In sporozoites, many mRNAs that are required for liver stage development are translationally repressed. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α leads to a global translational repression in sporozoites. The eIF2α kinase, known as Upregulated in Infectious Sporozoite 1 (UIS1, is dominant in the sporozoite. The eIF2α phosphatase, UIS2, is translationally repressed by the Pumilio protein Puf2. This translational repression is alleviated when sporozoites are delivered into the mammalian host.

  7. Translator-computer interaction in action

    DEFF Research Database (Denmark)

    Bundgaard, Kristine; Christensen, Tina Paulsen; Schjoldager, Anne

    2016-01-01

    perspective, this paper investigates the relationship between machines and humans in the field of translation, analysing a CAT process in which machine-translation (MT) technology was integrated into a translation-memory (TM) suite. After a review of empirical research into the impact of CAT tools......Though we lack empirically-based knowledge of the impact of computer-aided translation (CAT) tools on translation processes, it is generally agreed that all professional translators are now involved in some kind of translator-computer interaction (TCI), using O’Brien’s (2012) term. Taking a TCI......, the study indicates that the tool helps the translator conform to project and customer requirements....

  8. Create a translational medicine knowledge repository--research downsizing, mergers and increased outsourcing have reduced the depth of in-house translational medicine expertise and institutional memory at many pharmaceutical and biotech companies: how will they avoid relearning old lessons?

    Science.gov (United States)

    Littman, Bruce H; Marincola, Francesco M

    2011-05-10

    Pharmaceutical industry consolidation and overall research downsizing threatens the ability of companies to benefit from their previous investments in translational research as key leaders with the most knowledge of the successful use of biomarkers and translational pharmacology models are laid off or accept their severance packages. Two recently published books may help to preserve this type of knowledge but much of this type of information is not in the public domain. Here we propose the creation of a translational medicine knowledge repository where companies can submit their translational research data and access similar data from other companies in a precompetitive environment. This searchable repository would become an invaluable resource for translational scientists and drug developers that could speed and reduce the cost of new drug development.

  9. Create a translational medicine knowledge repository - Research downsizing, mergers and increased outsourcing have reduced the depth of in-house translational medicine expertise and institutional memory at many pharmaceutical and biotech companies: how will they avoid relearning old lessons?

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2011-05-01

    Full Text Available Abstract Pharmaceutical industry consolidation and overall research downsizing threatens the ability of companies to benefit from their previous investments in translational research as key leaders with the most knowledge of the successful use of biomarkers and translational pharmacology models are laid off or accept their severance packages. Two recently published books may help to preserve this type of knowledge but much of this type of information is not in the public domain. Here we propose the creation of a translational medicine knowledge repository where companies can submit their translational research data and access similar data from other companies in a precompetitive environment. This searchable repository would become an invaluable resource for translational scientists and drug developers that could speed and reduce the cost of new drug development.

  10. On the Systematicity of Human Translation Processes

    DEFF Research Database (Denmark)

    Carl, Michael; Dragsted, Barbara; Lykke Jakobsen, Arnt

    While translation careers and the translation profession become more globalised and more technological, we are still far from understanding how humans actually translate and how they could be best supported by machines. In this paper we attempt to outline a method which helps to uncover character......While translation careers and the translation profession become more globalised and more technological, we are still far from understanding how humans actually translate and how they could be best supported by machines. In this paper we attempt to outline a method which helps to uncover...... characteristic steps in human translation processes. Based on the translators' activity data, we develop a taxonomy of translation styles, which are characteristic for different kinds of translators. The taxonomy could serve to inform the development of advanced translation assistance tools and provide a basis...

  11. Salivary biomarkers associated with gingivitis and response to therapy.

    Science.gov (United States)

    Syndergaard, Ben; Al-Sabbagh, Mohanad; Kryscio, Richard J; Xi, Jing; Ding, Xiuhua; Ebersole, Jeffrey L; Miller, Craig S

    2014-08-01

    Salivary biomarkers are potentially important for determining the presence, risk, and progression of periodontal disease. However, clinical translation of biomarker technology from lab to chairside requires studies that identify biomarkers associated with the transitional phase between health and periodontal disease (i.e., gingivitis). Eighty participants (40 with gingivitis, 40 healthy) provided saliva at baseline and 7 to 30 days later. An additional sample was collected from gingivitis participants 10 to 30 days after dental prophylaxis. Clinical parameters of gingival disease were recorded at baseline and the final visit. Salivary concentrations of interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)-8, macrophage inflammatory protein (MIP)-1α, and prostaglandin E2 (PGE2) were measured. Clinical features of health and gingivitis were stable at both baseline visits. Participants with gingivitis demonstrated significantly higher bleeding on probing (BOP), plaque index (PI), and gingival index (GI) (P ≤0.002) and a significant drop in BOP, PI, and GI post-treatment (P ≤0.001). Concentrations of MIP-1α and PGE2 were significantly higher (2.8 times) in the gingivitis group than the healthy group (P ≤0.02). After dental prophylaxis, mean biomarker concentrations did not decrease significantly from baseline in the gingivitis group, although concentrations of IL-1β, IL-6, and MMP-8 approached healthy levels, whereas MIP-1α and PGE2 concentrations remained significantly higher than in the healthy group (P ≤0.04). Odds ratio analyses showed that PGE2 concentrations, alone and in combination with MIP-1α, readily discriminated gingivitis from health. Salivary PGE2 and MIP-1α discriminate gingivitis from health, and patients with gingivitis who return to clinical health continue to produce inflammatory mediators for weeks after dental prophylaxis.

  12. Early-Phase Studies of Biomarkers

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  13. Rostrocaudal Dynamics of CSF Biomarkers

    NARCIS (Netherlands)

    Tarnaris, A.; Toma, A.K.; Chapman, M.D.; Petzold, A.F.S.; Keir, G.; Kitchen, N.D.; Watkins, L.D.

    2011-01-01

    The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF) has not been studied adequately due to lack of appropriate control populations and ethical restrictions. The aim of this study is to understand the rostrocaudal gradient of CSF biomarkers. We contacted a study comparing

  14. Imaging Biomarkers for Adult Medulloblastomas

    DEFF Research Database (Denmark)

    Keil, V C; Warmuth-Metz, M; Reh, C

    2017-01-01

    BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences ...

  15. Biomarkers of satiation and satiety

    NARCIS (Netherlands)

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

    2004-01-01

    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

  16. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  17. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian

    2017-01-01

    biomarkers associated with PTB published from January 2005 to March 2014. Retrieved citations (3631) were screened, and relevant studies (33) were selected for full-text reading. Ten studies were included in the review. Forty-two PTB-related proteins were reported, and RANTES and IL-10 (three studies...

  18. Translation and Creative Writing: An Interview with Professor Margaret Rogers

    Directory of Open Access Journals (Sweden)

    Ruzbeh Babaee

    2016-01-01

    scandal? Is a translator accused of malpractice? MR: Of course, translators have to be aware that they can get sued if they make a translation error (e.g. mistranslating a number or a key term for financial and safety reasons respectively, and that they have a responsibility towards their client and their readers, but I think you have something else in mind here.   RB: What approach do you take in your translation workshops and classes? MR: An open discussion of the possibilities for translation, bearing in mind the purpose of the translation and the assumed expectations of target readers, even the environment in which the text is to be read or used, which might affect layout. The students’ own expectations can develop in a number of ways, through pair or group work, self-reflection, comparison of their own work with published translations, identification and evaluation of resources (increasingly online. Students understandably seek security when translating, for which the notion of the ‘perfect’ solution would, of course, be reassuring, were it not so elusive and misleading. That is not to say, however, that there is not on occasion a correct solution e.g. a company’s choice for the equivalent of a particular term, or an established standard. The overall goal is to establish through experience that the practice of translation is a decision-making process in which the translator’s agency is a key feature and to guide students towards tools and resources as well as developing evaluative skills to optimise this process. In my view, additional classes shared by students from different language groups can enrich this translation pair-specific experience by providing a systematic overview of different approaches to and issues in translation, enabling students to develop relevant points of reference for their decisions. Sometimes these classes are called ‘principles of translation’, ‘theory of translation’, ‘approaches to translation’, ‘translation

  19. Moderator's view: Patient-centered approaches for optimizing AKI management: the role of kidney biomarkers.

    Science.gov (United States)

    Mehta, Ravindra L

    2017-03-01

    Patients with acute kidney injury (AKI) continue to pose challenges for clinicians worldwide. Our understanding of the pathophysiology, epidemiology and course of the disease has improved significantly; however, this has not translated into any significant improvement in outcomes. Multiple new biomarkers have been developed to characterize the course of the disease and have been evaluated in multiple trials. Unfortunately, the adoption of biomarkers into routine clinical care has not been as expected. Several factors contribute to the slow uptake and can be addressed. This article provides a framework for a patient-centered approach to utilize biomarkers to improve patient care and outcomes in AKI. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  20. Use of biomarkers in the discovery of novel anti-schizophrenia drugs

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Thomsen, Morten S; Hansen, Henrik H

    2010-01-01

    Schizophrenia is characterized by a diverse symptomatology that often includes positive, cognitive and negative symptoms. Current anti-schizophrenic drugs act at multiple receptors, but little is known about how each of these receptors contributes to their mechanisms of action. Screening of novel...... anti-schizophrenic drug candidates targeting single receptors will be based on biomarker assays that measure signalling pathways, transcriptional factors, epigenetic mechanisms and synaptic function and translate these effects to behavioural effects in animals and humans. This review discusses current...

  1. Methionine sulfoxides in serum proteins as potential clinical biomarkers of oxidative stress

    OpenAIRE

    Satoko Suzuki; Yoshio Kodera; Tatsuya Saito; Kazumi Fujimoto; Akari Momozono; Akinori Hayashi; Yuji Kamata; Masayoshi Shichiri

    2016-01-01

    Oxidative stress contributes to the pathophysiology of a variety of diseases, and circulating biomarkers of its severity remains a topic of great interest for researchers. Our peptidomic strategy enables accurate and reproducible analysis of circulating proteins/peptides with or without post-translational modifications. Conventional wisdom holds that hydrophobic methionines exposed to an aqueous environment or experimental handling procedures are vulnerable to oxidation. However, we show that...

  2. Developing IAM for Life Cycle Safety Assessment

    NARCIS (Netherlands)

    Toxopeus, Marten E.; Lutters, Diederick; Nee, Andrew Y.C.; Song, Bin; Ong, Soh-Khim

    2013-01-01

    This publication discusses aspects of the development of an impact assessment method (IAM) for safety. Compared to the many existing IAM’s for environmentally oriented LCA, this method should translate the impact of a product life cycle on the subject of safety. Moreover, the method should be

  3. The current state of serum biomarkers of hepatotoxicity.

    Science.gov (United States)

    Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

    2008-03-20

    The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in

  4. The current state of serum biomarkers of hepatotoxicity

    International Nuclear Information System (INIS)

    Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

    2008-01-01

    The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTα) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early

  5. Systems biology and biomarker discovery

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.

    2010-12-01

    Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

  6. Localizing apps a practical guide for translators and translation students

    CERN Document Server

    Roturier, Johann

    2015-01-01

    The software industry has undergone rapid development since the beginning of the twenty-first century. These changes have had a profound impact on translators who, due to the evolving nature of digital content, are under increasing pressure to adapt their ways of working. Localizing Apps looks at these challenges by focusing on the localization of software applications, or apps. In each of the five core chapters, Johann Roturier examines:The role of translation and other linguistic activities in adapting software to the needs of different cultures (localization);The procedures required to prep

  7. Using example-based machine translation to translate DVD subtitles

    DEFF Research Database (Denmark)

    Flanagan, Marian

    between Swedish and Danish and Swedish and Norwegian subtitles, with the company already reporting a successful return on their investment. The hybrid EBMT/SMT system used in the current research, on the other hand, remains within the confines of academic research, and the real potential of the system...... allotted to produce the subtitles have both decreased. Therefore, this market is recognised as a potential real-world application of MT. Recent publications have introduced Corpus-Based MT approaches to translate subtitles. An SMT system has been implemented in a Swedish subtitling company to translate...

  8. Translational research: a concept analysis.

    Science.gov (United States)

    Wendler, M Cecilia; Kirkbride, Geri; Wade, Kristen; Ferrell, Lynne

    2013-01-01

    BACKGROUND/CONCEPTUAL FRAMEWORK: Little is known about which approaches facilitate adoption and sustainment of evidence-based practice change in the highly complex care environments that constitute clinical practice today. The purpose of this article was to complete a concept analysis of translational research using a modified Walker and Avant approach. DESIGN/DATA COLLECTION: Using a rigorous and thorough review of the recent health care literature generated by a deep electronic search from 2004-2011, 85 appropriate documents were retrieved. Close reading of the articles by three coresearchers yielded an analysis of the emerging concept of translational research. Using the iterative process described by Walker and Avant, a tentative definition of the concept of translational research, along with antecedents and consequences were identified. Implications for health care professionals in education, practice, and research are offered. Further research is needed to determine the adequacy of the definition, to identify empirical referents, and to guide theory development. The study resulted in a theoretical definition of the concept of translational research, along with identification of antecedents and consequences and a description of an ideal or model case to illustrate the definition. Implications for practice and education include the importance of focusing on translational research approaches that may reduce the research-practice gap in health care, thereby improving patient care delivery. Research is needed to determine the usefulness of the definition in health care clinical practice.

  9. Integrating Bioethics into Clinical and Translational Science Research: A Roadmap

    Science.gov (United States)

    Shapiro, Robyn S.; Layde, Peter M.

    2008-01-01

    Abstract Recent initiatives to improve human health emphasize the need to effectively and appropriately translate new knowledge gleaned from basic biomedical and behavioral research to clinical and community application. To maximize the beneficial impact of scientific advances in clinical practice and community health, and to guard against potential deleterious medical and societal consequences of such advances, incorporation of bioethics at each stage of clinical and translational science research is essential. At the earliest stage, bioethics input is critical to address issues such as whether to limit certain areas of scientific inquiry. Subsequently, bioethics input is important to assure not only that human subjects trials are conducted and reported responsibly, but also that results are incorporated into clinical and community practices in a way that promotes and protects bioethical principles. At the final stage of clinical and translational science research, bioethics helps to identify the need and approach for refining clinical practices when safety or other concerns arise. The framework we present depicts how bioethics interfaces with each stage of clinical and translational science research, and suggests an important research agenda for systematically and comprehensively assuring bioethics input into clinical and translational science initiatives. PMID:20443821

  10. Nuclear safety

    International Nuclear Information System (INIS)

    1991-02-01

    This book reviews the accomplishments, operations, and problems faced by the defense Nuclear Facilities Safety Board. Specifically, it discusses the recommendations that the Safety Board made to improve safety and health conditions at the Department of Energy's defense nuclear facilities, problems the Safety Board has encountered in hiring technical staff, and management problems that could affect the Safety Board's independence and credibility

  11. The Role of Semantics in Translation Recognition: Effects of Number of Translations, Dominance of Translations and Semantic Relatedness of Multiple Translations

    Science.gov (United States)

    Laxen, Jannika; Lavaur, Jean-Marc

    2010-01-01

    This study aims to examine the influence of multiple translations of a word on bilingual processing in three translation recognition experiments during which French-English bilinguals had to decide whether two words were translations of each other or not. In the first experiment, words with only one translation were recognized as translations…

  12. Working with Corpora in the Translation Classroom

    Science.gov (United States)

    Krüger, Ralph

    2012-01-01

    This article sets out to illustrate possible applications of electronic corpora in the translation classroom. Starting with a survey of corpus use within corpus-based translation studies, the didactic value of corpora in the translation classroom and their epistemic value in translation teaching and practice will be elaborated. A typology of…

  13. Translation Ambiguity in and out of Context

    Science.gov (United States)

    Prior, Anat; Wintner, Shuly; MacWhinney, Brian; Lavie, Alon

    2011-01-01

    We compare translations of single words, made by bilingual speakers in a laboratory setting, with contextualized translation choices of the same items, made by professional translators and extracted from parallel language corpora. The translation choices in both cases show moderate convergence, demonstrating that decontextualized translation…

  14. Daisaku Ikeda and the Culture of Translation

    Science.gov (United States)

    Gebert, Andrew

    2012-01-01

    Although not functionally multilingual or a translator himself, Daisaku Ikeda has been deeply involved in translation processes, both as a reader and as someone who has produced texts for translation into various languages. This article examines two sources of influence shaping Ikeda's attitude toward translation culture: the flourishing culture…

  15. Barriers vs Creativity in Translator Training

    Science.gov (United States)

    Yazici, Mine

    2016-01-01

    This paper discusses translation problems awaiting Turkish students as well as the creative solutions they develop in overcoming them. It consists of two parts; The first part studies the barriers concerning translation procedures from the perspective of translation theory and Turkish translation history; The second parts analyses the impact of…

  16. Allocation of Cognitive Resources in Translation

    DEFF Research Database (Denmark)

    Hvelplund, Kristian Tangsgaard

    The present study is an empirical investigation of translators' allocation of cognitive resources during the translation process, and it aims at investigating how translators' mental processing resources are put to use during translation. The study bases ts analyses on quantitative eye...

  17. Translational informatics: an industry perspective.

    Science.gov (United States)

    Cantor, Michael N

    2012-01-01

    Translational informatics (TI) is extremely important for the pharmaceutical industry, especially as the bar for regulatory approval of new medications is set higher and higher. This paper will explore three specific areas in the drug development lifecycle, from tools developed by precompetitive consortia to standardized clinical data collection to the effective delivery of medications using clinical decision support, in which TI has a major role to play. Advancing TI will require investment in new tools and algorithms, as well as ensuring that translational issues are addressed early in the design process of informatics projects, and also given higher weight in funding or publication decisions. Ultimately, the source of translational tools and differences between academia and industry are secondary, as long as they move towards the shared goal of improving health.

  18. A Taxonomy of Human Translation Styles

    DEFF Research Database (Denmark)

    Carl, Michael; Dragsted, Barbara; Lykke Jakobsen, Arnt

    2011-01-01

    on the translators' activity data, we develop a taxonomy of translation styles. The taxonomy could serve to inform the development of advanced translation assistance tools and provide a basis for a felicitous and grounded integration of human machine interaction in translation.......While the translation profession becomes increasingly technological, we are still far from understanding how humans actually translate and how they could be best supported by machines. In this paper we outline a method which helps to uncover characteristics of human translation processes. Based...

  19. History and theory of Scripture translations

    Directory of Open Access Journals (Sweden)

    Jean-Claude Loba-Mkole

    2008-01-01

    Full Text Available This article argues for the importance of Bible translations through its historical achievements and theoretical frames of reference. The missionary expansion of Christianity owes its very being to translations. The early Christian communities knew the Bible through the LXX translations while churches today still continue to use various translations. Translations shape Scripture interpretations, especially when a given interpretation depends on a particular translation. A particular interpretation can also influence a given translation. The article shows how translation theories have been developed to clarify and how the transaction source-target is culturally handled. The articles discuss some of these “theoretical frames”, namely the functional equivalence, relevance, literary functional equivalence and intercultural mediation. By means of a historical overview and a reflection on Bible translation theories the article aims to focus on the role of Africa in translation history.

  20. Translation Technologies: A Dilemma between Translation Industry and Academia

    Science.gov (United States)

    Bakul, Halil Ibrahim

    2016-01-01

    Today, physical and virtual borders are shrinking thanks to technology whose footprints are greater and faster than one can imagine. Beyond the shadow of a doubt, technology is associated with the areas for which it offers solutions such as education technologies, health technologies and translation technologies. Nowadays using translation…

  1. The translator status, the translation market and developing ...

    African Journals Online (AJOL)

    Southern African Linguistics and Applied Language Studies ... article is an attempt to examine the sociology of translation in the development context of ten countries in the Association of Southeast Asian Nations (Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand and Vietnam).

  2. Nurturing and Testing Translation Competence for Text-Translating

    Science.gov (United States)

    Aubakirova, Karlygash Adilkhanovna

    2016-01-01

    The article analyzes the problems of contemporary professional education. As its instance, we examine the developmental scheme for training professional translators. Optimal ways of organizing the learning process are suggested from the point of view of the competence approach, which is widely recognized for training a modern specialist. The…

  3. JavaScript DNA translator: DNA-aligned protein translations.

    Science.gov (United States)

    Perry, William L

    2002-12-01

    There are many instances in molecular biology when it is necessary to identify ORFs in a DNA sequence. While programs exist for displaying protein translations in multiple ORFs in alignment with a DNA sequence, they are often expensive, exist as add-ons to software that must be purchased, or are only compatible with a particular operating system. JavaScript DNA Translator is a shareware application written in JavaScript, a scripting language interpreted by the Netscape Communicator and Internet Explorer Web browsers, which makes it compatible with several different operating systems. While the program uses a familiar Web page interface, it requires no connection to the Internet since calculations are performed on the user's own computer. The program analyzes one or multiple DNA sequences and generates translations in up to six reading frames aligned to a DNA sequence, in addition to displaying translations as separate sequences in FASTA format. ORFs within a reading frame can also be displayed as separate sequences. Flexible formatting options are provided, including the ability to hide ORFs below a minimum size specified by the user. The program is available free of charge at the BioTechniques Software Library (www.Biotechniques.com).

  4. Implementation of proteomic biomarkers: making it work.

    Science.gov (United States)

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

    2012-09-01

    While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

  5. Biomarkers of PTSD: military applications and considerations

    Directory of Open Access Journals (Sweden)

    Amy Lehrner

    2014-08-01

    Full Text Available Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. Objective: This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Method: Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Results: Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Conclusions: Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  6. Biomarkers of PTSD: military applications and considerations.

    Science.gov (United States)

    Lehrner, Amy; Yehuda, Rachel

    2014-01-01

    Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  7. Implementation of proteomic biomarkers: making it work

    Science.gov (United States)

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

    2012-01-01

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

  8. Legal Translation Dictionaries for Learners

    DEFF Research Database (Denmark)

    Nielsen, Sandro

    2010-01-01

    in conditional clauses. When translating into languages not allowing such structures, for instance, English and French, learners need their legal translation dictionaries to help them with both the legal terms and the syntactic structures. The uses of textual conventions that characterise the legal genre vary....... Lexicographers should therefore design their dictionaries so that they contain intra-lingual or contrastive descriptions of the relevant genre conventions. As illustrated in Nielsen (2000) whether the best solution is to retain the genre conventions found in the SL text or to adopt the conventions used in TL...

  9. Proteomic and metabolomic approaches to biomarker discovery

    CERN Document Server

    Issaq, Haleem J

    2013-01-01

    Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

  10. 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.

    2008-05-01

    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.

  11. Clinical Macrosystem Simulation Translates Between Organizations.

    Science.gov (United States)

    Bender, G Jesse; Maryman, James A

    2018-04-01

    Simulation has become an integral tool in healthcare facility redesign. Immersing clinical experts into their future environment has demonstrated benefits for transition planning. This study evaluates translation of a proven macrosystems testing protocol, TESTPILOT, to an organization with limited simulation experience. An experienced TESTPILOT team guided Woman's Hospital Baton Rouge's simulation preparation for their new neonatal intensive care unit. Metrics included participant evaluations, latent safety threats (LST), and clinician surveys. Latent safety threats recorded during debriefings were addressed by workflow committees. Clinicians were surveyed at four time points for readiness and preparedness on 24 key processes. The local team invested nearly 750 hours into learning and implementing seven simulations that participants rated positively. Most of the 305 LST were minor issues. Surveys at baseline (42% of staff), postsim (18%), pretransition (26%), and postmove (29%) demonstrated strong internal consistency. System readiness lagged behind staff preparedness (P structure, team coverage, and feedback were still evolving as of move day (P organizations with limited prior exposure. Woman's Hospital Baton Rouge accrued essential skills to model and orchestrate an immersive neonatal intensive care unit and then drive effective multidisciplinary debriefings. Staff immersed in the new environment began to articulate their jobs before moving in. The trajectory of system readiness improvement corroborated LST correction. Future research is needed to determine the extent of simulation required for different organizational structures.

  12. Geometry and topology of wild translation surfaces

    OpenAIRE

    Randecker, Anja

    2016-01-01

    A translation surface is a two-dimensional manifold, equipped with a translation structure. It can be obtained by considering Euclidean polygons and identifying their edges via translations. The vertices of the polygons form singularities if the translation structure can not be extended to them. We study translation surfaces with wild singularities, regarding the topology (genus and space of ends), the geometry (behavior of the singularities), and how the topology and the geometry are related.

  13. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  14. Nuclear safety

    International Nuclear Information System (INIS)

    Tarride, Bruno

    2015-10-01

    The author proposes an overview of methods and concepts used in the nuclear industry, at the design level as well as at the exploitation level, to ensure an acceptable safety level, notably in the case of nuclear reactors. He first addresses the general objectives of nuclear safety and the notion of acceptable risk: definition and organisation of nuclear safety (relationships between safety authorities and operators), notion of acceptable risk, deterministic safety approach and main safety principles (safety functions and confinement barriers, concept of defence in depth). Then, the author addresses the safety approach at the design level: studies of operational situations, studies of internal and external aggressions, safety report, design principles for important-for-safety systems (failure criterion, redundancy, failure prevention, safety classification). The next part addresses safety during exploitation and general exploitation rules: definition of the operation domain and of its limits, periodic controls and tests, management in case of incidents, accidents or aggressions

  15. From differences in means between cases and controls to risk stratification: a business plan for biomarker development.

    Science.gov (United States)

    Wentzensen, Nicolas; Wacholder, Sholom

    2013-02-01

    Researchers developing biomarkers for early detection can determine the potential for clinical benefit at early stages of development. We provide the theoretical background showing the quantitative connection between biomarker levels in cases and controls and clinically meaningful risk measures, as well as a spreadsheet for researchers to use in their own research. We provide researchers with tools to decide whether a test is useful, whether it needs technical improvement, whether it may work only in specific populations, or whether any further development is futile. The methods described here apply to any method that aims to estimate risk of disease based on biomarkers, clinical tests, genetics, environment, or behavior. Many efforts go into futile biomarker development and premature clinical testing. In many instances, predictions for translational success or failure can be made early, simply based on critical analysis of case–control data. Our article presents well-established theory in a form that can be appreciated by biomarker researchers. Furthermore, we provide an interactive spreadsheet that links biomarker performance with specific disease characteristics to evaluate the promise of biomarker candidates at an early stage.

  16. Safety culture

    International Nuclear Information System (INIS)

    Keen, L.J.

    2003-01-01

    Safety culture has become a topic of increasing interest for industry and regulators as issues are raised on safety problems around the world. The keys to safety culture are organizational effectiveness, effective communications, organizational learning, and a culture that encourages the identification and resolution of safety issues. The necessity of a strong safety culture places an onus on all of us to continually question whether the safety measures already in place are sufficient, and are being applied. (author)

  17. Translational research: precision medicine, personalized medicine, targeted therapies: marketing or science?

    Science.gov (United States)

    Marquet, Pierre; Longeray, Pierre-Henry; Barlesi, Fabrice; Ameye, Véronique; Augé, Pascale; Cazeneuve, Béatrice; Chatelut, Etienne; Diaz, Isabelle; Diviné, Marine; Froguel, Philippe; Goni, Sylvia; Gueyffier, François; Hoog-Labouret, Natalie; Mourah, Samia; Morin-Surroca, Michèle; Perche, Olivier; Perin-Dureau, Florent; Pigeon, Martine; Tisseau, Anne; Verstuyft, Céline

    2015-01-01

    Personalized medicine is based on: 1) improved clinical or non-clinical methods (including biomarkers) for a more discriminating and precise diagnosis of diseases; 2) targeted therapies of the choice or the best drug for each patient among those available; 3) dose adjustment methods to optimize the benefit-risk ratio of the drugs chosen; 4) biomarkers of efficacy, toxicity, treatment discontinuation, relapse, etc. Unfortunately, it is still too often a theoretical concept because of the lack of convenient diagnostic methods or treatments, particularly of drugs corresponding to each subtype of pathology, hence to each patient. Stratified medicine is a component of personalized medicine employing biomarkers and companion diagnostics to target the patients likely to present the best benefit-risk balance for a given active compound. The concept of targeted therapy, mostly used in cancer treatment, relies on the existence of a defined molecular target, involved or not in the pathological process, and/or on the existence of a biomarker able to identify the target population, which should logically be small as compared to the population presenting the disease considered. Targeted therapies and biomarkers represent important stakes for the pharmaceutical industry, in terms of market access, of return on investment and of image among the prescribers. At the same time, they probably represent only the first generation of products resulting from the combination of clinical, pathophysiological and molecular research, i.e. of translational research. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  18. (Configuring gender in Bible translation: Cultural, translational and gender critical intersections

    Directory of Open Access Journals (Sweden)

    Jeremy Punt

    2014-06-01

    Full Text Available The gendered intersection of cultural studies and Bible translation is under acknowledged. Accounting for gender criticism in translation work requires, besides responsible theory and practice of translation, also attention to interwoven gender critical aspects. After a brief investigation of the intersections between biblical, translation and gender studies, translation in a few Pauline texts with bearing on gender and sexuality are investigated.

  19. Chronic Obstructive Pulmonary Disease Biomarkers

    Directory of Open Access Journals (Sweden)

    Tatsiana Beiko

    2016-04-01

    Full Text Available Despite significant decreases in morbidity and mortality of cardiovascular diseases (CVD and cancers, morbidity and cost associated with chronic obstructive pulmonary disease (COPD continue to be increasing. Failure to improve disease outcomes has been related to the paucity of interventions improving survival. Insidious onset and slow progression halter research successes in developing disease-modifying therapies. In part, the difficulty in finding new therapies is because of the extreme heterogeneity within recognized COPD phenotypes. Novel biomarkers are necessary to help understand the natural history and pathogenesis of the different COPD subtypes. A more accurate phenotyping and the ability to assess the therapeutic response to new interventions and pharmaceutical agents may improve the statistical power of longitudinal clinical studies. In this study, we will review known candidate biomarkers for COPD, proposed pathways of pathogenesis, and future directions in the field.

  20. Glycoscience aids in biomarker discovery

    Directory of Open Access Journals (Sweden)

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

    2012-06-01

    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.

  1. Candidate immune biomarkers for radioimmunotherapy.

    Science.gov (United States)

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

    2017-08-01

    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. Copyright © 2017. Published by Elsevier B.V.

  2. Hurdles in Basic Science Translation

    Directory of Open Access Journals (Sweden)

    Christina J. Perry

    2017-07-01

    Full Text Available In the past century there have been incredible advances in the field of medical research, but what hinders translation of this knowledge into effective treatment for human disease? There is an increasing focus on the failure of many research breakthroughs to be translated through the clinical trial process and into medical practice. In this mini review, we will consider some of the reasons that findings in basic medical research fail to become translated through clinical trials and into basic medical practices. We focus in particular on the way that human disease is modeled, the understanding we have of how our targets behave in vivo, and also some of the issues surrounding reproducibility of basic research findings. We will also look at some of the ways that have been proposed for overcoming these issues. It appears that there needs to be a cultural shift in the way we fund, publish and recognize quality control in scientific research. Although this is a daunting proposition, we hope that with increasing awareness and focus on research translation and the hurdles that impede it, the field of medical research will continue to inform and improve medical practice across the world.

  3. Advancing neurosurgery through translational research.

    Science.gov (United States)

    Lacey, Claire; Sutherland, Garnette

    2013-01-01

    Every year, the number of published research articles increases significantly. However, many potentially useful ideas are lost in this flood of data. Translational research provides a framework through which investigators or laboratories can maximize the likelihood that the product of their research will be adopted in medical practice. There are 2 recognizable models of translation appropriate for the majority of research: investigator driven and industry enabled. Investigator-driven research has more range because it does not have to consider the profit margin of research, but it is a slow process. The industry-enabled model accelerates the translational research process through the power of industry funding but is interested primarily in products with potential for profit. Two cases are examined to illustrate different methods of partnering with industry. IMRIS is a company founded by investigators to distribute intraoperative magnetic resonance imaging technology based on a movable high-field magnet. It took 7 years for IMRIS to make its first sale, but it is now a successful company. With neuroArm, a surgical robot, investigators decided to sell the intellectual property to an established company to ensure successful global commercialization. Translational research advances medicine by creating and distributing effective solutions to contemporary problems.

  4. Machine Translation - A Gentle Introduction

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 7. Machine Translation - A Gentle Introduction. Durgesh D Rao. General Article Volume 3 Issue 7 July 1998 pp 61-70. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/003/07/0061-0070 ...

  5. Translational Research and Youth Development

    Science.gov (United States)

    Hamilton, Stephen F.

    2015-01-01

    Borrowing the term "translational research" (TR) from medicine, along with some of the ideas and practices that define it, holds promise as a way of linking research more closely to the practice of youth development. However, doing so entails substantial adaptation. TR is more than a new name for applied research. It comprehends the…

  6. Translational medicine and drug discovery

    National Research Council Canada - National Science Library

    Littman, Bruce H; Krishna, Rajesh

    2011-01-01

    ..., and examples of their application to real-life drug discovery and development. The latest thinking is presented by researchers from many of the world's leading pharmaceutical companies, including Pfizer, Merck, Eli Lilly, Abbott, and Novartis, as well as from academic institutions and public- private partnerships that support translational research...

  7. Parsing statistical machine translation output

    NARCIS (Netherlands)

    Carter, S.; Monz, C.; Vetulani, Z.

    2009-01-01

    Despite increasing research into the use of syntax during statistical machine translation, the incorporation of syntax into language models has seen limited success. We present a study of the discriminative abilities of generative syntax-based language models, over and above standard n-gram models,

  8. Random glycopeptide bead libraries for seromic biomarker discovery

    DEFF Research Database (Denmark)

    Kracun, Stjepan Kresimir; Cló, Emiliano; Clausen, Henrik

    2010-01-01

    have developed a random glycopeptide bead library screening platform for detection of autoantibodies and other binding proteins. Libraries were build on biocompatible PEGA beads including a safety-catch C-terminal amide linker (SCAL) that allowed mild cleavage conditions (I(2)/NaBH(4) and TFA...... to other tumor glycoforms by on-bead enzymatic glycosylation reactions with recombinant glycosyltransferases. Hence, we have developed a high-throughput flexible platform for rapid discovery of O-glycopeptide biomarkers and the method has applicability in other types of assays such as lectin...

  9. Biomarkers in adult posthemorrhagic hydrocephalus.

    Science.gov (United States)

    Hua, Cong; Zhao, Gang

    2017-08-01

    Posthemorrhagic hydrocephalus is a severe complication following intracranial hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity and mortality and serves as an important clinical predictor of adverse outcomes after intracranial hemorrhage. Currently, no effective medical intervention exists to improve functional outcomes in posthemorrhagic hydrocephalus patients because little is still known about the mechanisms of posthemorrhagic hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic hydrocephalus pathogenesis would facilitate development of clinical treatments, this is an active research area. The purpose of this review is to describe recent progress in elucidation of molecular mechanisms that cause posthemorrhagic hydrocephalus. What we are certain of is that the entry of blood into the ventricular system and subarachnoid space results in release of lytic blood products which cause a series of physiological and pathological changes in the brain. Blood components that can be linked to pathology would serve as disease biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus progression. These findings suggest that modulation of biomarker expression or function may benefit posthemorrhagic hydrocephalus patients.

  10. WONOEP appraisal: Development of epilepsy biomarkers-What we can learn from our patients?

    Science.gov (United States)

    Jozwiak, Sergiusz; Becker, Albert; Cepeda, Carlos; Engel, Jerome; Gnatkovsky, Vadym; Huberfeld, Gilles; Kaya, Mehmet; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A

    2017-06-01

    Current medications for patients with epilepsy work in only two of three patients. For those medications that do work, they only suppress seizures. They treat the symptoms, but do not modify the underlying disease, forcing patients to take these drugs with significant side effects, often for the rest of their lives. A major limitation in our ability to advance new therapeutics that permanently prevent, reduce the frequency of, or cure epilepsy comes from a lack of understanding of the disease coupled with a lack of reliable biomarkers that can predict who has or who will get epilepsy. The main goal of this report is to present a number of approaches for identifying reliable biomarkers from observing patients with brain disorders that have a high probability of producing epilepsy. A given biomarker, or more likely a profile of biomarkers, will have both a quantity and a time course during epileptogenesis that can be used to predict who will get the disease, to confirm epilepsy as a diagnosis, to identify coexisting pathologies, and to monitor the course of treatments. Additional studies in patients and animal models could identify common and clinically valuable biomarkers to successfully translate animal studies into new and effective clinical trials. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  11. MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer

    International Nuclear Information System (INIS)

    Pal, Manish K.; Jaiswar, Shyam P.; Dwivedi, Vinaya N.; Tripathi, Amit K.; Dwivedi, Ashish; Sankhwar, Pushplata

    2015-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers (mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as microRNAs (miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood samples of cancer patients. Therefore, miRNAs hold good promise as potential biomarkers in ovarian cancer. In this review, we attempted to provide a comprehensive profile of key miRNAs involved in ovarian carcinoma to establish miRNAs as more reliable non-invasive clinical biomarkers for early detection of ovarian cancer compared with protein and DNA biomarkers

  12. Evaluation of safety practices and performance in a brewery industry ...

    African Journals Online (AJOL)

    Michael Horsfall

    prevented in the period of the safety programme which translates to an average of 19.45 per year. The safety programme ... due to “weak safeguards against occupational and .... outputs within such a system. In this ..... Journal of Disaster Prevention and Management: ... Duignan, T. (2003), “Good health and safety is good.

  13. Translators’ Use of Digital Resources during Translation

    DEFF Research Database (Denmark)

    Hvelplund, Kristian Tangsgaard

    2017-01-01

    This paper presents the findings from a study on translators’ use of digital resources during the translation process. Eye tracking data and screen recording data from 18 professional translators are analysed in order to 1) examine how much time translators spend on digital resource consultation...... compared with translation drafting and translation revision, 2) examine how eye movements differ between translation drafting, revision and digital resource consultation and 3) investigate what types of digital resources are used by translators. The findings demonstrate that digital resource consultation...... constitutes a considerable amount of the translation process. The findings also show longer fixations and larger pupils during resource consultation, indicating heavier cognitive load, and finally the study identifies considerable variation in the use of resources between translators....

  14. ERRORS AND DIFFICULTIES IN TRANSLATING LEGAL TEXTS

    Directory of Open Access Journals (Sweden)

    Camelia, CHIRILA

    2014-11-01

    Full Text Available Nowadays the accurate translation of legal texts has become highly important as the mistranslation of a passage in a contract, for example, could lead to lawsuits and loss of money. Consequently, the translation of legal texts to other languages faces many difficulties and only professional translators specialised in legal translation should deal with the translation of legal documents and scholarly writings. The purpose of this paper is to analyze translation from three perspectives: translation quality, errors and difficulties encountered in translating legal texts and consequences of such errors in professional translation. First of all, the paper points out the importance of performing a good and correct translation, which is one of the most important elements to be considered when discussing translation. Furthermore, the paper presents an overview of the errors and difficulties in translating texts and of the consequences of errors in professional translation, with applications to the field of law. The paper is also an approach to the differences between languages (English and Romanian that can hinder comprehension for those who have embarked upon the difficult task of translation. The research method that I have used to achieve the objectives of the paper was the content analysis of various Romanian and foreign authors' works.

  15. A GRAMMATICAL ADJUSTMENT ANALYSIS OF STATISTICAL MACHINE TRANSLATION METHOD USED BY GOOGLE TRANSLATE COMPARED TO HUMAN TRANSLATION IN TRANSLATING ENGLISH TEXT TO INDONESIAN

    Directory of Open Access Journals (Sweden)

    Eko Pujianto

    2017-04-01

    Full Text Available Google translate is a program which provides fast, free and effortless translating service. This service uses a unique method to translate. The system is called ―Statistical Machine Translation‖, the newest method in automatic translation. Machine translation (MT is an area of many kinds of different subjects of study and technique from linguistics, computers science, artificial intelligent (AI, translation theory, and statistics. SMT works by using statistical methods and mathematics to process the training data. The training data is corpus-based. It is a compilation of sentences and words of the languages (SL and TL from translation done by human. By using this method, Google let their machine discovers the rules for themselves. They do this by analyzing millions of documents that have already been translated by human translators and then generate the result based on the corpus/training data. However, questions arise when the results of the automatic translation prove to be unreliable in some extent. This paper questions the dependability of Google translate in comparison with grammatical adjustment that naturally characterizes human translators' specific advantage. The attempt is manifested through the analysis of the TL of some texts translated by the SMT. It is expected that by using the sample of TL produced by SMT we can learn the potential flaws of the translation. If such exists, the partial of more substantial undependability of SMT may open more windows to the debates of whether this service may suffice the users‘ need.

  16. Typologically robust statistical machine translation : Understanding and exploiting differences and similarities between languages in machine translation

    NARCIS (Netherlands)

    Daiber, J.

    2018-01-01

    Machine translation systems often incorporate modeling assumptions motivated by properties of the language pairs they initially target. When such systems are applied to language families with considerably different properties, translation quality can deteriorate. Phrase-based machine translation

  17. Reactor safety

    International Nuclear Information System (INIS)

    Butz, H.P.; Heuser, F.W.; May, H.

    1985-01-01

    The paper comprises an introduction into nuclear physics bases, the safety concept generally speaking, safety devices of pwr type reactors, accident analysis, external influences, probabilistic safety assessment and risk studies. It further describes operational experience, licensing procedures under the Atomic Energy Law, research in reactor safety and the nuclear fuel cycle. (DG) [de

  18. Translation: between what can be translated and what must be translated

    Directory of Open Access Journals (Sweden)

    Magda Jeanrenaud

    2016-02-01

    Full Text Available Starting from a disconcerting interpretation of Jacques Derrida, our analysis aims at investigating and also tries to explain the blockage which appears in the English, French and Romanian translations (signed by Maurice de Gandillac, Antoine Berman, Laurent Lamy, Alexis Nouss, Harry Zohn, Steven Rendall, Martine Broda, Catrinel Pleșu etc. of a well-known text of Walter Benjamin, Die Aufgabe des Übersetzers, when translators transpose in their target languages the two quotations given by Benjamin: one of Mallarmé, left untranslated in the source text, and another, signed by Pannwitz. The fact is that both quotations have something in common: a discoursive form which results from an unusual syntax, as if they were already, in a certain sense, „translations”. As if the translators feared—a feature of the translator’s psychology?—not to render their text sufficiently accessible, even when the source text is not intended to be accessible. Hence the painful dilemma of the intentional fallacy (not only of the text to be translated.

  19. Authorial and Editorial Voices in Translation

    DEFF Research Database (Denmark)

    Translation Studies now recognizes that translators are not the only agents involved in translation. Authors and editors provide suggestions and instructions. Publishers have considerable power over the final text and how it is presented to the public. While it is well-known that translations...... understanding of the processes through which authors, publishers, editors, directors, and critics can affect translation. Empirical studies from historical and contemporary settings examine forms of collaboration and negotiation, or conflict, with special attention to the multiple voices in theatre translation....

  20. Advancing translational research with the Semantic Web.

    Science.gov (United States)

    Ruttenberg, Alan; Clark, Tim; Bug, William; Samwald, Matthias; Bodenreider, Olivier; Chen, Helen; Doherty, Donald; Forsberg, Kerstin; Gao, Yong; Kashyap, Vipul; Kinoshita, June; Luciano, Joanne; Marshall, M Scott; Ogbuji, Chimezie; Rees, Jonathan; Stephens, Susie; Wong, Gwendolyn T; Wu, Elizabeth; Zaccagnini, Davide; Hongsermeier, Tonya; Neumann, Eric; Herman, Ivan; Cheung, Kei-Hoi

    2007-05-09

    A fundamental goal of the U.S. National Institute of Health (NIH) "Roadmap" is to strengthen Translational Research, defined as the movement of discoveries in basic research to application at the clinical level. A significant barrier to translational research is the lack of uniformly structured data across related biomedical domains. The Semantic Web is an extension of the current Web that enables navigation and meaningful use of digital resources by automatic processes. It is based on common formats that support aggregation and integration of data drawn from diverse sources. A variety of technologies have been built on this foundation that, together, support identifying, representing, and reasoning across a wide range of biomedical data. The Semantic Web Health Care and Life Sciences Interest Group (HCLSIG), set up within the framework of the World Wide Web Consortium, was launched to explore the application of these technologies in a variety of areas. Subgroups focus on making biomedical data available in RDF, working with biomedical ontologies, prototyping clinical decision support systems, working on drug safety and efficacy communication, and supporting disease researchers navigating and annotating the large amount of potentially relevant literature. We present a scenario that shows the value of the information environment the Semantic Web can support for aiding neuroscience researchers. We then report on several projects by members of the HCLSIG, in the process illustrating the range of Semantic Web technologies that have applications in areas of biomedicine. Semantic Web technologies present both promise and challenges. Current tools and standards are already adequate to implement components of the bench-to-bedside vision. On the other hand, these technologies are young. Gaps in standards and implementations still exist and adoption is limited by typical problems with early technology, such as the need for a critical mass of practitioners and installed base

  1. An analysis of machine translation and speech synthesis in speech-to-speech translation system

    OpenAIRE

    Hashimoto, K.; Yamagishi, J.; Byrne, W.; King, S.; Tokuda, K.

    2011-01-01

    This paper provides an analysis of the impacts of machine translation and speech synthesis on speech-to-speech translation systems. The speech-to-speech translation system consists of three components: speech recognition, machine translation and speech synthesis. Many techniques for integration of speech recognition and machine translation have been proposed. However, speech synthesis has not yet been considered. Therefore, in this paper, we focus on machine translation and speech synthesis, ...

  2. Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

    International Nuclear Information System (INIS)

    Gautier, Jean-Charles; Zhou, Xiaobing; Yang, Yi; Gury, Thierry; Qu, Zhe; Palazzi, Xavier; Léonard, Jean-François; Slaoui, Mohamed; Veeranagouda, Yaligara; Guizon, Isabelle; Boitier, Eric; Filali-Ansary, Aziz; Berg, Bart H.J. van den; Poetz, Oliver; Joos, Thomas; Zhang, Tianyi; Wang, Jufeng; Detilleux, Philippe; Li, Bo

    2016-01-01

    Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- and multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.

  3. Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

    Energy Technology Data Exchange (ETDEWEB)

    Gautier, Jean-Charles, E-mail: jean-charles.gautier@sanofi.com [Sanofi R& D, Vitry-sur-Seine (France); Zhou, Xiaobing [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Yang, Yi [Sanofi R& D, Bridgewater (United States); Gury, Thierry [Sanofi R& D, Vitry-sur-Seine (France); Qu, Zhe [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Palazzi, Xavier; Léonard, Jean-François; Slaoui, Mohamed; Veeranagouda, Yaligara; Guizon, Isabelle; Boitier, Eric; Filali-Ansary, Aziz [Sanofi R& D, Vitry-sur-Seine (France); Berg, Bart H.J. van den; Poetz, Oliver; Joos, Thomas [Natural and Medical Sciences Institute at the University Tübingen (Germany); Zhang, Tianyi [Frontage Laboratories, Shanghai (China); Wang, Jufeng [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Detilleux, Philippe [Sanofi R& D, Vitry-sur-Seine (France); Li, Bo, E-mail: libo@nifdc.org.cn [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China)

    2016-07-15

    Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- and multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.

  4. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Gudjonsson, Thorkell; Nielsen, Ole Haagen

    2011-01-01

    on the current understanding of the pathogenesis of ulcerative colitis-associated colorectal cancer and how this knowledge can be transferred into patient management to assist clinicians and pathologists in identifying patients with ulcerative colitis who have an increased risk of colorectal cancer. Inflammation......One of the most serious complications of ulcerative colitis is the development of colorectal cancer. Screening patients with ulcerative colitis by standard histological examination of random intestinal biopsy samples might be inefficient as a method of cancer surveillance. This Review focuses......-driven mechanisms of DNA damage, including the generation and effects of reactive oxygen species, microsatellite instability, telomere shortening and chromosomal instability, are reviewed, as are the molecular responses to genomic stress. We also discuss how these mechanisms can be translated into usable biomarkers...

  5. Mass Spectrometry-based Assay for High Throughput and High Sensitivity Biomarker Verification

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xuejiang; Tang, Keqi

    2017-06-14

    , also known as multiple reaction monitoring (MRM), is capable of quantitatively measuring hundreds of candidate protein biomarkers from a relevant clinical sample in a single analysis. The specificity, reproducibility and sensitivity could be as good as ELISA. Furthermore, SRM MS can also quantify protein isoforms and post-translational modifications, for which traditional antibody-based immunoassays often don’t exist.

  6. From Polarity to Plurality in Translation Scholarship

    Directory of Open Access Journals (Sweden)

    Abdolla Karimzadeh

    2012-09-01

    Full Text Available Review of the literature in translation studies shows that translation scholarship can be discussed in 3 Macro-levels including 1 Corpus-based studies, 2 Protocol-based studies, and 3 Systems- based studies. Researchers in the corpus-based studies test the hypothesis about the universals of translation. They also try to identify translation norms and regular linguistic patterns. This scholarship aims at showing that the language of translation is different from that of non-translation. The other purpose is to identify the techniques and strategies adopted by the translators. In protocol –based studies, the researchers study the mental activities and the individual behaviors of the translators while translating. They aim to describe the behavior of professional translators (versus translator trainees during the process of translation in a bid to identify how they chunk the source text (unit of translation and to describe how the translation trainees develop their translation competence. These studies are longitudinal for the reason that they aim to investigate the change of intended behaviors in the subjects of the study. Like corpus-based studies, they are experimental and data for analysis are collected by various methods including the translators’ verbal report, keystroke logging, eye tracking, and so on. Recently, in a method called “triangulation”, they combine the above-mentioned methods of data collection to test their hypotheses on a stronger experimental basis. To collect the data, they also employ the methods used in neurology (for example the technology of Electroencephalogram in order to obtain information on the physiological processes in the brains of the translators while translating. And finally in the systems-based studies, the researchers analyze more extended systems of production, distribution, and consumption of translations and their impacts on the target culture in a specific socio-cultural context. Differentiating

  7. Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization.

    Science.gov (United States)

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

    2015-07-01

    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. © 2015 American Society for Clinical Pharmacology and Therapeutics.

  8. Biomarkers of carcinogen exposure and early effects.

    OpenAIRE

    2006-01-01

    The purpose of this review is to summarise the current situation regarding the types and uses of biomarkers of exposure and effect for the main classes of food-derived genotoxic carcinogens, and to consider some aspects of the intercomparison between these biomarkers. The biomarkers of exposure and early effects of carcinogens that have been most extensively developed are those for genotoxic agents and for compounds that generate hydroxyl radicals and other reactive radical species, and it is...

  9. Biomarkers of HIV-associated Cancer

    OpenAIRE

    Flepisi, Brian Thabile; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd

    2014-01-01

    Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of can...

  10. Biomarkers of PTSD: military applications and considerations

    OpenAIRE

    Amy Lehrner; Rachel Yehuda

    2014-01-01

    Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk fo...

  11. Translational research on advanced therapies

    Directory of Open Access Journals (Sweden)

    Filippo Belardelli

    2011-01-01

    Full Text Available Fostering translational research of advanced therapies has become a major priority of both scientific community and national governments. Advanced therapy medicinal products (ATMP are a new medicinal product category comprising gene therapy and cell-based medicinal products as well as tissue engineered medicinal products. ATMP development opens novel avenues for therapeutic approaches in numerous diseases, including cancer and neurodegenerative and cardiovascular diseases. However, there are important bottlenecks for their development due to the complexity of the regulatory framework, the high costs and the needs for good manufacturing practice (GMP facilities and new end-points for clinical experimentation. Thus, a strategic cooperation between different stakeholders (academia, industry and experts in regulatory issues is strongly needed. Recently, a great importance has been given to research infrastructures dedicated to foster translational medicine of advanced therapies. Some ongoing European initiatives in this field are presented and their potential impact is discussed.

  12. Translational research on advanced therapies.

    Science.gov (United States)

    Belardelli, Filippo; Rizza, Paola; Moretti, Franca; Carella, Cintia; Galli, Maria Cristina; Migliaccio, Giovanni

    2011-01-01

    Fostering translational research of advanced therapies has become a major priority of both scientific community and national governments. Advanced therapy medicinal products (ATMP) are a new medicinal product category comprising gene therapy and cell-based medicinal products as well as tissue engineered medicinal products. ATMP development opens novel avenues for therapeutic approaches in numerous diseases, including cancer and neurodegenerative and cardiovascular diseases. However, there are important bottlenecks for their development due to the complexity of the regulatory framework, the high costs and the needs for good manufacturing practice (GMP) facilities and new end-points for clinical experimentation. Thus, a strategic cooperation between different stakeholders (academia, industry and experts in regulatory issues) is strongly needed. Recently, a great importance has been given to research infrastructures dedicated to foster translational medicine of advanced therapies. Some ongoing European initiatives in this field are presented and their potential impact is discussed.

  13. Translation Competence and Translation Performance: Lexical, Syntactic and Textual Patterns in Student Translations of a Specialized EU Genre

    Science.gov (United States)

    Karoly, Adrienn

    2012-01-01

    This paper reports the findings of a study aiming to reveal the recurring patterns of lexical, syntactic and textual errors in student translations of a specialized EU genre from English into Hungarian. By comparing the student translations to the official translation of the text, this article uncovers the most frequent errors that students made…

  14. Cardiovascular biomarkers in clinical studies of type 2 diabetes

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  15. Livestock models in translational medicine.

    Science.gov (United States)

    Roth, James A; Tuggle, Christopher K

    2015-01-01

    This issue of the ILAR Journal focuses on livestock models in translational medicine. Livestock models of selected human diseases present important advantages as compared with rodent models for translating fundamental breakthroughs in biology to useful preventatives and therapeutics for humans. Livestock reflect the complexity of applying medical advances in an outbred species. In many cases, the pathogenesis of infectious, metabolic, genetic, and neoplastic diseases in livestock species more closely resembles that in humans than does the pathogenesis of rodent models. Livestock models also provide the advantage of similar organ size and function and the ability to serially sample an animal throughout the study period. Research using livestock models for human disease often benefits not only human health but animal health and food production as well. This issue of the ILAR Journal presents information on translational research using livestock models in two broad areas: microbiology and infectious disease (transmissible spongiform encephalopathies, mycobacterial infections, influenza A virus infection, vaccine development and testing, the human microbiota) and metabolic, neoplastic, and genetic disorders (stem cell therapy, male germ line cell biology, pulmonary adenocarcinoma, muscular dystrophy, wound healing). In addition, there is a manuscript devoted to Institutional Animal Care and Use Committees' responsibilities for reviewing research using livestock models. Conducting translational research using livestock models requires special facilities and researchers with expertise in livestock. There are many institutions in the world with experienced researchers and facilities designed for livestock research; primarily associated with colleges of agriculture and veterinary medicine or government laboratories. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions

  16. The ubiquity of conservative translations

    Czech Academy of Sciences Publication Activity Database

    Jeřábek, Emil

    2012-01-01

    Roč. 5, č. 4 (2012), s. 666-678 ISSN 1755-0203 R&D Projects: GA AV ČR IAA100190902; GA MŠk(CZ) 1M0545 Institutional support: RVO:67985840 Keywords : conservative translation * deductive system * nonclassical logic Subject RIV: BA - General Mathematics Impact factor: 0.500, year: 2012 http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8757256

  17. Hemopexin as biomarkers for analyzing the biological responses associated with exposure to silica nanoparticles

    Science.gov (United States)

    Higashisaka, Kazuma; Yoshioka, Yasuo; Yamashita, Kohei; Morishita, Yuki; Pan, Huiyan; Ogura, Toshinobu; Nagano, Takashi; Kunieda, Akiyoshi; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Tsutsumi, Yasuo

    2012-10-01

    Practical uses of nanomaterials are rapidly spreading to a wide variety of fields. However, potential harmful effects of nanomaterials are raising concerns about their safety. Therefore, it is important that a risk assessment system is developed so that the safety of nanomaterials can be evaluated or predicted. Here, we attempted to identify novel biomarkers of nanomaterial-induced health effects by a comprehensive screen of plasma proteins using two-dimensional differential in gel electrophoresis (2D-DIGE) analysis. Initially, we used 2D-DIGE to analyze changes in the level of plasma proteins in mice after intravenous injection via tail veins of 0.8 mg/mouse silica nanoparticles with diameters of 70 nm (nSP70) or saline as controls. By quantitative image analysis, protein spots representing >2.0-fold alteration in expression were found and identified by mass spectrometry. Among these proteins, we focused on hemopexin as a potential biomarker. The levels of hemopexin in the plasma increased as the silica particle size decreased. In addition, the production of hemopexin depended on the characteristics of the nanomaterials. These results suggested that hemopexin could be an additional biomarker for analyzing the biological responses associated with exposure to silica nanoparticles. We believe that this study will contribute to the development of biomarkers to ensure the safety of silica nanoparticles.

  18. Biomarker Development for TLR4 Agonists

    National Research Council Canada - National Science Library

    Persing, David H

    2004-01-01

    .... To monitor the effectiveness of immunoprophylaxis in human trials, it may become necessary to develop surrogate biomarkers of protection since experimental challenge endpoints are not readily available...

  19. Searching for Clinically Relevant Biomarkers in Geriatric Oncology.

    Science.gov (United States)

    Katsila, Theodora; Patrinos, George P; Kardamakis, Dimitrios

    2018-01-01

    Ageing, which is associated with a progressive decline and functional deterioration in multiple organ systems, is highly heterogeneous, both inter- and intraindividually. For this, tailored-made theranostics and optimum patient stratification become fundamental, when decision-making in elderly patients is considered. In particular, when cancer incidence and cancer-related mortality and morbidity are taken into account, elderly patient care is a public health concern. In this review, we focus on oncogeriatrics and highlight current opportunities and challenges with an emphasis on the unmet need of clinically relevant biomarkers in elderly cancer patients. We performed a literature search on PubMed and Scopus databases for articles published in English between 2000 and 2017 coupled to text mining and analysis. Considering the top insights, we derived from our literature analysis that information knowledge needs to turn into knowledge growth in oncogeriatrics towards clinically relevant biomarkers, cost-effective practices, updated educational schemes for health professionals (in particular, geriatricians and oncologists), and awareness of ethical issues. We conclude with an interdisciplinary call to omics, geriatricians, oncologists, informatics, and policy-makers communities that Big Data should be translated into decision-making in the clinic.

  20. Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Aldo Bonaventura

    2016-11-01

    Full Text Available After an acute ischemic stroke (AIS, inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies.

  1. Multi-dimensional discovery of biomarker and phenotype complexes

    Directory of Open Access Journals (Sweden)

    Huang Kun

    2010-10-01

    Full Text Available Abstract Background Given the rapid growth of translational research and personalized healthcare paradigms, the ability to relate and reason upon networks of bio-molecular and phenotypic variables at various levels of granularity in order to diagnose, stage and plan treatments for disease states is highly desirable. Numerous techniques exist that can be used to develop networks of co-expressed or otherwise related genes and clinical features. Such techniques can also be used to create formalized knowledge collections based upon the information incumbent to ontologies and domain literature. However, reports of integrative approaches that bridge such networks to create systems-level models of disease or wellness are notably lacking in the contemporary literature. Results In response to the preceding gap in knowledge and practice, we report upon a prototypical series of experiments that utilize multi-modal approaches to network induction. These experiments are intended to elicit meaningful and significant biomarker-phenotype complexes spanning multiple levels of granularity. This work has been performed in the experimental context of a large-scale clinical and basic science data repository maintained by the National Cancer Institute (NCI funded Chronic Lymphocytic Leukemia Research Consortium. Conclusions Our results indicate that it is computationally tractable to link orthogonal networks of genes, clinical features, and conceptual knowledge to create multi-dimensional models of interrelated biomarkers and phenotypes. Further, our results indicate that such systems-level models contain interrelated bio-molecular and clinical markers capable of supporting hypothesis discovery and testing. Based on such findings, we propose a conceptual model intended to inform the cross-linkage of the results of such methods. This model has as its aim the identification of novel and knowledge-anchored biomarker-phenotype complexes.

  2. Systematic reviews and knowledge translation.

    Science.gov (United States)

    Tugwell, Peter; Robinson, Vivian; Grimshaw, Jeremy; Santesso, Nancy

    2006-08-01

    Proven effective interventions exist that would enable all countries to meet the Millennium Development Goals. However, uptake and use of these interventions in the poorest populations is at least 50% less than in the richest populations within each country. Also, we have recently shown that community effectiveness of interventions is lower for the poorest populations due to a "staircase" effect of lower coverage/access, worse diagnostic accuracy, less provider compliance and less consumer adherence. We propose an evidence-based framework for equity-oriented knowledge translation to enhance community effectiveness and health equity. This framework is represented as a cascade of steps to assess and prioritize barriers and thus choose effective knowledge translation interventions that are tailored for relevant audiences (public, patient, practitioner, policy-maker, press and private sector), as well as the evaluation, monitoring and sharing of these strategies. We have used two examples of effective interventions (insecticide-treated bednets to prevent malaria and childhood immunization) to illustrate how this framework can provide a systematic method for decision-makers to ensure the application of evidence-based knowledge in disadvantaged populations. Future work to empirically validate and evaluate the usefulness of this framework is needed. We invite researchers and implementers to use the cascade for equity-oriented knowledge translation as a guide when planning implementation strategies for proven effective interventions. We also encourage policy-makers and health-care managers to use this framework when deciding how effective interventions can be implemented in their own settings.

  3. Translation of ARAC computer codes

    International Nuclear Information System (INIS)

    Takahashi, Kunio; Chino, Masamichi; Honma, Toshimitsu; Ishikawa, Hirohiko; Kai, Michiaki; Imai, Kazuhiko; Asai, Kiyoshi

    1982-05-01

    In 1981 we have translated the famous MATHEW, ADPIC and their auxiliary computer codes for CDC 7600 computer version to FACOM M-200's. The codes consist of a part of the Atmospheric Release Advisory Capability (ARAC) system of Lawrence Livermore National Laboratory (LLNL). The MATHEW is a code for three-dimensional wind field analysis. Using observed data, it calculates the mass-consistent wind field of grid cells by a variational method. The ADPIC is a code for three-dimensional concentration prediction of gases and particulates released to the atmosphere. It calculates concentrations in grid cells by the particle-in-cell method. They are written in LLLTRAN, i.e., LLNL Fortran language and are implemented on the CDC 7600 computers of LLNL. In this report, i) the computational methods of the MATHEW/ADPIC and their auxiliary codes, ii) comparisons of the calculated results with our JAERI particle-in-cell, and gaussian plume models, iii) translation procedures from the CDC version to FACOM M-200's, are described. Under the permission of LLNL G-Division, this report is published to keep the track of the translation procedures and to serve our JAERI researchers for comparisons and references of their works. (author)

  4. XML Translator for Interface Descriptions

    Science.gov (United States)

    Boroson, Elizabeth R.

    2009-01-01

    A computer program defines an XML schema for specifying the interface to a generic FPGA from the perspective of software that will interact with the device. This XML interface description is then translated into header files for C, Verilog, and VHDL. User interface definition input is checked via both the provided XML schema and the translator module to ensure consistency and accuracy. Currently, programming used on both sides of an interface is inconsistent. This makes it hard to find and fix errors. By using a common schema, both sides are forced to use the same structure by using the same framework and toolset. This makes for easy identification of problems, which leads to the ability to formulate a solution. The toolset contains constants that allow a programmer to use each register, and to access each field in the register. Once programming is complete, the translator is run as part of the make process, which ensures that whenever an interface is changed, all of the code that uses the header files describing it is recompiled.

  5. Revisiting interaction in knowledge translation

    Directory of Open Access Journals (Sweden)

    Zackheim Lisa

    2007-10-01

    Full Text Available Abstract Background Although the study of research utilization is not new, there has been increased emphasis on the topic over the recent past. Science push models that are researcher driven and controlled and demand pull models emphasizing users/decision-maker interests have largely been abandoned in favour of more interactive models that emphasize linkages between researchers and decisionmakers. However, despite these and other theoretical and empirical advances in the area of research utilization, there remains a fundamental gap between the generation of research findings and the application of those findings in practice. Methods Using a case approach, the current study looks at the impact of one particular interaction approach to research translation used by a Canadian funding agency. Results Results suggest there may be certain conditions under which different levels of decisionmaker involvement in research will be more or less effective. Four attributes are illuminated by the current case study: stakeholder diversity, addressability/actionability of results, finality of study design and methodology, and politicization of results. Future research could test whether these or other variables can be used to specify some of the conditions under which different approaches to interaction in knowledge translation are likely to facilitate research utilization. Conclusion This work suggests that the efficacy of interaction approaches to research translation may be more limited than current theory proposes and underscores the need for more completely specified models of research utilization that can help address the slow pace of change in this area.

  6. The translational metaphor in psychoanalysis.

    Science.gov (United States)

    Kirshner, Lewis

    2015-02-01

    The translational metaphor in psychoanalysis refers to the traditional method of interpreting or restating the meaning of verbal and behavioral acts of a patient in other, presumably more accurate terms that specify the forces and conflicts underlying symptoms. The analyst translates the clinical phenomenology to explain its true meaning and origin. This model of analytic process has been challenged from different vantage points by authors presenting alternative conceptions of therapeutic action. Although the temptation to find and make interpretations of clinical material is difficult to resist, behaving in this way places the analyst in the position of a teacher or diagnostician, seeking a specific etiology, which has not proven fruitful. Despite its historical appeal, I argue that the translational model is a misleading and anachronistic version of what actually occurs in psychoanalysis. I emphasize instead the capacity of analysis to promote the emergence of new forms of representation, or figuration, from the unconscious, using the work of Lacan, Laplanche, and Modell to exemplify this reformulation, and provide clinical illustrations of how it looks in practice. Copyright © 2014 Institute of Psychoanalysis.

  7. Translational pharmacology of dopamine receptor agonists and antagonists : prolactin and oxytocin as biomarkers

    NARCIS (Netherlands)

    Stevens, Jasper

    2011-01-01

    For mechanism-based investigations on PK-PD relationships following intranasal administration, the use of advanced animal models and analytical techniques are crucial. As described in this thesis, quantitative information on distinction between extent as well as rate of absorption between

  8. Diagnostic Biomarkers for Posttraumatic Stress Disorder (PTSD): Promising Horizons from Translational Neuroscience Research

    OpenAIRE

    Michopoulos, Vasiliki; Norrholm, Seth Davin; Jovanovic, Tanja

    2015-01-01

    Posttraumatic stress disorder (PTSD) is a heterogeneous disorder that affects individuals exposed to trauma (e.g., combat, interpersonal violence, and natural disasters). Although its diagnostic features have been recently re-classified with the emergence of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5), the disorder remains characterized by hyperarousal, intrusive reminders of the trauma, avoidance of trauma-related cues, and negative cognition and mood. T...

  9. Translating Management Practices in Hierarchical Organizations

    DEFF Research Database (Denmark)

    Wæraas, Arild; Nielsen, Jeppe Agger

    structures affect translators’ approaches taken towards management ideas. This paper reports the findings from a longitudinal case study of the translation of Leadership Pipeline in a Danish fire department and how the translators’ approach changed over time from a modifying to a reproducing mode. The study......This study examines how translators in a hierarchical context approach the translation of management practices. Although current translation theory and research emphasize the importance of contextual factors in translation processes, little research has investigated how strongly hierarchical...... finds that translation does not necessarily imply transformation of the management idea, pointing instead to aspects of exact imitation and copying of an ”original” idea. It also highlights how translation is likely to involve multiple and successive translation modes and, furthermore, that strongly...

  10. Classroom Interactions in a Cooperative Translation Task

    Directory of Open Access Journals (Sweden)

    Hui chuan Wang

    2013-03-01

    Full Text Available For the past decade, translation learning has become one of the main foci for university language students in Taiwan. However, many studies have shown that translation teachers tend to adopt traditional teaching methods without considering class dynamics and student interactions. This paper therefore looks into the interactions in the researcher’s designed cooperative translation task, the Cooperative Translation Task, to see how these interactions helped or hindered students’ translation learning. A small class of 25 translation students and two translation teachers were participants. Videotaping and interviews were conducted in order to investigate the interaction modes and student participants’ perspectives toward each interaction mode. Six interaction modes were found in this task: within group, between group, translator group and comment-giver group, instructor and students, guest teacher and students, and instructor and guest teacher. Based on the results and participants’ responses, suggested teaching guidelines are provided.

  11. (CEPTSA) — Translating and Explanatory Dictionaries

    African Journals Online (AJOL)

    The phases of the project, consisting of different translating and explanatory versions, are discussed. ... already published, namely the Dictionary category of the South African Translators' Institute (SATI) (2003), ... AJOL African Journals Online.

  12. Morphological Analysis for Statistical Machine Translation

    National Research Council Canada - National Science Library

    Lee, Young-Suk

    2004-01-01

    .... The technique improves Arabic-to-English translation qualities significantly when applied to IBM Model 1 and Phrase Translation Models trained on the training corpus size ranging from 3,500 to 3.3 million sentence pairs.

  13. Precision axial translator with high stability.

    Science.gov (United States)

    Bösch, M A

    1979-08-01

    We describe a new type of translator which is inherently stable against torsion and twisting. This concentric translator is also ideally suited for precise axial motion with clearance of the center line.

  14. Translator/Revisor | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    On request, performs quality control of texts translated or written by clients or ... of the Official Languages Act, the IDRC Translation Unit provides service for the ... Resources and Communications documents for the purposes of internal and ...

  15. Serum Antibody Biomarkers for ASD

    Science.gov (United States)

    2015-10-01

    typically developing control. US, unaffected sibling control. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a...typically developing (TD) children (e.g., Warren et al., 1990; Singh, 2009). The goal of this study is to identify a serum antibody biomarker for ASD using...50% less IgG1 antibody in ASD boys vs . TD boys (p=0.0096). The level of ASD1 binding to the AM group was the same as to the ASD boys. These data

  16. The Translation of Chinese Dish Names

    Institute of Scientific and Technical Information of China (English)

    龚佳文

    2015-01-01

    The traditional food of a nation reflects its historical and cultural characteristics This thesis begins with an introduction to the translation situation of Chinese dish names and its existing problem nowadays, and proceeds to the translation principles and tactics for English translation of the names of Chinese dishes, based on Eugene A. Nida’ s Functional Equivalence, with an aim to improve translation efficiency and promote cross-cultural communication, and promoting Chinese food culture throughout the globe.

  17. Preserved Network Metrics across Translated Texts

    Science.gov (United States)

    Cabatbat, Josephine Jill T.; Monsanto, Jica P.; Tapang, Giovanni A.

    2014-09-01

    Co-occurrence language networks based on Bible translations and the Universal Declaration of Human Rights (UDHR) translations in different languages were constructed and compared with random text networks. Among the considered network metrics, the network size, N, the normalized betweenness centrality (BC), and the average k-nearest neighbors, knn, were found to be the most preserved across translations. Moreover, similar frequency distributions of co-occurring network motifs were observed for translated texts networks.

  18. Single acting translational/rotational brake

    Science.gov (United States)

    Allred, Johnny W. (Inventor); Fleck, Jr., Vincent J. (Inventor)

    1996-01-01

    A brake system is provided that applies braking forces on surfaces in both the translational and rotational directions using a single acting self-contained actuator that travels with the translational mechanism. The brake engages a mechanical lock and creates a frictional force on the translational structure preventing translation while simultaneously creating a frictional torque that prevents rotation of the vertical support. The system may include serrations on the braking surfaces to provide increased braking forces.

  19. Common Marmosets: A Potential Translational Animal Model of Juvenile Depression

    Directory of Open Access Journals (Sweden)

    Nicole Leite Galvão-Coelho

    2017-09-01

    Full Text Available Major depression is a psychiatric disorder with high prevalence in the general population, with increasing expression in adolescence, about 14% in young people. Frequently, it presents as a chronic condition, showing no remission even after several pharmacological treatments and persisting in adult life. Therefore, distinct protocols and animal models have been developed to increase the understanding of this disease or search for new therapies. To this end, this study investigated the effects of chronic social isolation and the potential antidepressant action of nortriptyline in juvenile Callithrix jacchus males and females by monitoring fecal cortisol, body weight, and behavioral parameters and searching for biomarkers and a protocol for inducing depression. The purpose was to validate this species and protocol as a translational model of juvenile depression, addressing all domain criteria of validation: etiologic, face, functional, predictive, inter-relational, evolutionary, and population. In both sexes and both protocols (IDS and DPT, we observed a significant reduction in cortisol levels in the last phase of social isolation, concomitant with increases in autogrooming, stereotyped and anxiety behaviors, and the presence of anhedonia. The alterations induced by chronic social isolation are characteristic of the depressive state in non-human primates and/or in humans, and were reversed in large part by treatment with an antidepressant drug (nortriptyline. Therefore, these results indicate C. jacchus as a potential translational model of juvenile depression by addressing all criteria of validation.

  20. Professional Communication and Translation in Convergence

    DEFF Research Database (Denmark)

    Gnecci, Marusca; Maylath, Bruce; Mousten, Birthe

    2008-01-01

    As translation of technical documents becomes commonplace, and as translation becomes more automated, the roles of translator and technical communicator appear to be converging. This paper examines the trend revealed from recent surveys, and it suggests further research to determine if the trend...... is likely to continue. The  paper also provides recommendations for academic programs interested in adjusting to the trend....

  1. Evidence of Parallel Processing During Translation

    DEFF Research Database (Denmark)

    Balling, Laura Winther; Hvelplund, Kristian Tangsgaard; Sjørup, Annette Camilla

    2014-01-01

    conclude that translation is a parallel process and that literal translation is likely to be a universal initial default strategy in translation. This conclusion is strengthened by the fact that all three experiments were relatively naturalistic, due to the combination of remote eye tracking and mixed...

  2. Difficulties in translation of personality scales

    DEFF Research Database (Denmark)

    Simonsen, Erik; Mortensen, Erik Lykke

    1990-01-01

    This paper discusses translations of tests and questionnaires from a psychological perspective: A distinction is drawn between linguistic and psychometric considerations, and procedures from both areas are briefly described. Back-translations and simple psychometric procedures are used to illustr...... to illustrate problems in the translation of Millon's Clinical Multiaxial Inventory into Danish....

  3. Machine Translation in Post-Contemporary Era

    Science.gov (United States)

    Lin, Grace Hui Chin

    2010-01-01

    This article focusing on translating techniques via personal computer or laptop reports updated artificial intelligence progresses before 2010. Based on interpretations and information for field of MT [Machine Translation] by Yorick Wilks' book, "Machine Translation, Its scope and limits," this paper displays understandable theoretical frameworks…

  4. Professional Communication and Translation in Convergence

    DEFF Research Database (Denmark)

    Gnecci, Marusca; Maylath, Bruce; Mousten, Birthe

    2008-01-01

    As translation of technical documents becomes commonplace, and as translation becomes more automated, the roles of translator and technical communicator appear to be converging. This paper examines the trend revealed from recent surveys, and it suggests further research to determine if the trend...

  5. The Role of Translation in EFL Writing

    Directory of Open Access Journals (Sweden)

    congmin zhao

    2017-12-01

    Full Text Available This paper explores the problem “thinking in the first language then translating into the target language” by examining the process of writing. It is suggested that it is natural to think in the first language and/or to translate and the first language to foreign language translation indirectly enhances the writing ability.

  6. The Role of Translation in EFL Writing

    OpenAIRE

    congmin zhao

    2017-01-01

    This paper explores the problem “thinking in the first language then translating into the target language” by examining the process of writing. It is suggested that it is natural to think in the first language and/or to translate and the first language to foreign language translation indirectly enhances the writing ability.

  7. Traveling Chaucer: Comparative Translation and Cosmopolitan Humanism

    Science.gov (United States)

    Barrington, Candace

    2014-01-01

    Through the comparative study of non-Anglophone translations of Geoffrey Chaucer's "The Canterbury Tales," we can achieve the progressive goals of Emily Apter's "translational transnationalism" and Edward Said's "cosmopolitan humanism." Both translation and humanism were intrinsic to Chaucer's…

  8. Inhibiting Translation One Protein at a Time.

    Science.gov (United States)

    Disney, Matthew D

    2017-06-01

    Historically, translational inhibitors have been confined to anti-bacterials that globally affect translation. Lintner et al. demonstrate that small molecules can specifically inhibit translation of a single disease-associated protein by stalling the ribosome's nascent chain [1], opening up a new therapeutic strategy for 'undruggable' proteins. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Development and Validation of a Translation Test.

    Science.gov (United States)

    Ghonsooly, Behzad

    1993-01-01

    Translation testing methodology has been criticized for its subjective character. No real strides have so far been made in developing an objective translation test. In this paper, certain detailed procedures including various phases of pretesting have been performed to achieve objectivity and scorability in translation testing methodology. In…

  10. Translation Factors Specify Cellular Metabolic State

    Directory of Open Access Journals (Sweden)

    Juan Mata

    2016-08-01

    Full Text Available In this issue of Cell Reports, Shah et al. present evidence that a subcomplex of the eIF3 translation initiation factor regulates translation of mRNAs encoding components of the mitochondrial electron transport chain and glycolytic enzymes, thus linking translational control with energy metabolism.

  11. High-Speed Maglev Trains; German Safety Requirements

    Science.gov (United States)

    1991-12-31

    This document is a translation of technology-specific safety requirements developed : for the German Transrapid Maglev technology. These requirements were developed by a : working group composed of representatives of German Federal Railways (DB), Tes...

  12. Translation and development of the BNWL-geosphere model

    International Nuclear Information System (INIS)

    Grundfelt, B.

    1977-02-01

    The report deals with the rate of radioactivity discharge from a repository for radioactive waste in a geologic formation to the biosphere. A BASIC language computer program called GETOUT has been developed in USA. It was obtained by the Swedish project Nuclear Fuel Safety and has thereafter been translated into FORTRAN. The main extension of the code, that was made during the translation, is a model for averaging the hydrodynamic and geochemical parameters for the case of non-uniform packing of the column (e.g. considering a repository in cracked rock with crack width, crack spacing etc. in different zones). The program has been outtested on an IBM model 360/75 computer. The migration is governed by three parameters i.e. the ground water velocity, the dispersion coefficient and the nuclide retentivities. (L.B.)

  13. [Current status and prospect of translational medicine in nanotechnology].

    Science.gov (United States)

    Gao, Guang-yu; Chen, Mei-ling; Li, Ming-yuan; Yang, Zhen-bo; Li, Zhi-ping; Mei, Xing-guo

    2015-08-01

    Nowadays, nanotechnologies have shown wide application foreground in the biomedical field of medicine laboratory tests, drug delivery, gene therapy and bioremediation. However, in recent years, nanomaterials have been labeled poisonous, because of the disputes and misunderstandings of mainstream views on their safety. Besides, for the barriers of technical issues in preparation like: (1) low efficacy (poor PK & PD and low drug loading), (2) high cost (irreproducibility and difficulty in scale up), little of that research has been successfully translated into commercial products. Currently, along with the new theory of "physical damage is the origin of nanotoxicity", biodegradability and biocompatibility of nanomaterials are listed as the basic principle of safe application of nanomaterials. Combining scientific design based on molecular level with precision control of process engineering will provide a new strategy to overcome the core technical challenges. New turning point of translational medicine in nanotechnology may emerge.

  14. Measuring Difficulty in English-Chinese Translation: Towards a General Model of Translation Difficulty

    Science.gov (United States)

    Sun, Sanjun

    2012-01-01

    Accurate assessment of a text's level of translation difficulty is critical for translator training and accreditation, translation research, and the language industry as well. Traditionally, people rely on their general impression to gauge a text's translation difficulty level. If the evaluation process is to be more effective and the…

  15. How Do English Translation Majors Use Translation Strategies? A Survey of the Iranian EFL Context

    Science.gov (United States)

    Asgarian, Amir; Vefali, Gülsen Musayeva

    2015-01-01

    Translation language learning strategies, especially in relation to translation students, have not received adequate attention in the research to date. Therefore, the present study attempted to explore Iranian translation students' use of translation strategies, related beliefs, and academic achievement. It was a survey study involving…

  16. Translating Proper Nouns: A Case Study on English Translation of Hafez's Lyrics

    Science.gov (United States)

    Shirinzadeh, Seyed Alireza; Mahadi, Tengku Sepora Tengku

    2014-01-01

    Proper nouns are regarded so simple that they might be taken for granted in translation explorations. Some may believe that they should not be translated in transmitting source texts to target texts. But, it is not the case; if one looks at present translations, he will notice that different strategies might be applied for translating proper…

  17. Vaccine Safety

    Science.gov (United States)

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  18. SAFETY FIRST

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Ensuring safety while peacefully utilizing nuclear energy is a top priority for China A fter a recent earthquake in Japan caused radioactive leaks at a nuclear power plant in Tokyo, the safety of nuclear energy has again aroused public attention.

  19. ITER safety

    International Nuclear Information System (INIS)

    Raeder, J.; Piet, S.; Buende, R.

    1991-01-01

    As part of the series of publications by the IAEA that summarize the results of the Conceptual Design Activities for the ITER project, this document describes the ITER safety analyses. It contains an assessment of normal operation effluents, accident scenarios, plasma chamber safety, tritium system safety, magnet system safety, external loss of coolant and coolant flow problems, and a waste management assessment, while it describes the implementation of the safety approach for ITER. The document ends with a list of major conclusions, a set of topical remarks on technical safety issues, and recommendations for the Engineering Design Activities, safety considerations for siting ITER, and recommendations with regard to the safety issues for the R and D for ITER. Refs, figs and tabs

  20. Water Safety

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Water Safety KidsHealth / For Parents / Water Safety What's in ... remains your best measure of protection. Making Kids Water Wise It's important to teach your kids proper ...