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Sample records for combining multiple diagnostic

  1. Measuring and combining multiple diagnostic and prognostic sepsis biomarkers

    DEFF Research Database (Denmark)

    Kofoed, Kristian

    2008-01-01

    of findings from other studies. The results showed that CRP and PCT had acceptable, sTREM-1 and MIF limited, and suPAR no use in diagnostic bacterial infection in this group of patients. However, in regard to the prognostic capability the opposite was found; suPAR showed promising results for the prediction...... of mortality during the first 30 days post admission, while no difference was found in admission levels of either CRP or PCT between survivors or non-survivors. By combining the single measurements we constructed a 6-marker test. This test was significantly better than any of the single markers in diagnosing...... bacterial infection. In conclusion, a biomarker profile, containing multiple markers for risk assessment and diagnosis in patients with suspected sepsis, could be a future way to improve sepsis outcome....

  2. Diagnostic challenges in combined multiple sclerosis and centronuclear myopathy

    DEFF Research Database (Denmark)

    Olsen, D.B.; Langkilde, Annika Reynberg; Schmalbruch, H

    2000-01-01

    The first case of combined centronuclear myopathy and multiple sclerosis is reported. The difficulties of diagnosing multiple sclerosis in patients with muscular disorders associated with the central nervous system involvement are discussed...

  3. Diagnostic challenges in combined multiple sclerosis and centronuclear myopathy

    DEFF Research Database (Denmark)

    Olsen, D.B.; Langkilde, Annika Reynberg; Schmalbruch, H

    2000-01-01

    The first case of combined centronuclear myopathy and multiple sclerosis is reported. The difficulties of diagnosing multiple sclerosis in patients with muscular disorders associated with the central nervous system involvement are discussed......The first case of combined centronuclear myopathy and multiple sclerosis is reported. The difficulties of diagnosing multiple sclerosis in patients with muscular disorders associated with the central nervous system involvement are discussed...

  4. A simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification

    Directory of Open Access Journals (Sweden)

    Amin Manik A

    2006-10-01

    Full Text Available Abstract Background In spite of the recognized diagnostic potential of biomarkers, the quest for squelching noise and wringing in information from a given set of biomarkers continues. Here, we suggest a statistical algorithm that – assuming each molecular biomarker to be a diagnostic test – enriches the diagnostic performance of an optimized set of independent biomarkers employing established statistical techniques. We validated the proposed algorithm using several simulation datasets in addition to four publicly available real datasets that compared i subjects having cancer with those without; ii subjects with two different cancers; iii subjects with two different types of one cancer; and iv subjects with same cancer resulting in differential time to metastasis. Results Our algorithm comprises of three steps: estimating the area under the receiver operating characteristic curve for each biomarker, identifying a subset of biomarkers using linear regression and combining the chosen biomarkers using linear discriminant function analysis. Combining these established statistical methods that are available in most statistical packages, we observed that the diagnostic accuracy of our approach was 100%, 99.94%, 96.67% and 93.92% for the real datasets used in the study. These estimates were comparable to or better than the ones previously reported using alternative methods. In a synthetic dataset, we also observed that all the biomarkers chosen by our algorithm were indeed truly differentially expressed. Conclusion The proposed algorithm can be used for accurate diagnosis in the setting of dichotomous classification of disease states.

  5. Multiple sclerosis - etiology and diagnostic potential.

    Science.gov (United States)

    Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

    2017-06-30

    Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

  6. Reproducibility of 24-hour combined multiple intraluminal impedance (MII) and pH measurements in infants and children. Evaluation of a diagnostic procedure for gastroesophageal reflux disease

    DEFF Research Database (Denmark)

    Dalby, Kasper; Nielsen, Rasmus G; Markoew, Simone

    2007-01-01

    Gastroesophageal reflux disease (GERD) is a common disease in infants and children. Prolonged (24-hr) pH monitoring in the esophagus for determination of increased acid exposure has, together with endoscopy, been the only routinely implemented method for GERD diagnosis. The recently introduced...... multiple intraluminal impedance (MII) provides additional information about the number of both acid and nonacid episodes of retrograde bolus movement in the esophagus. The aim of this study was to investigate the day-to-day reproducibility and the interobserver variability of 24-hr combined MII (number...... of nonacid and acidic reflux episodes) and pH in the esophagus in infants and children. Upper endoscopy followed by 2 x 24-hr consecutive combined MII and pH monitoring was performed in 33 infants and children referred to a tertiary center for evaluation of GERD. The study was performed in a hospital setting...

  7. Multiple sclerosis - etiology and diagnostic potential

    Directory of Open Access Journals (Sweden)

    Joanna Kamińska

    2017-06-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS, secondary progressive multiple sclerosis (SPSM, primary progressive multiple sclerosis (PPMS, and progressive-relapsing multiple sclerosis (RPMS. Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald’s diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI, cerebrospinal fluid (CSF analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of differentdiagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

  8. Multiple diagnostic approaches to palpable breast mass

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Soo Yil; Kim, Kie Hwan; Moon, Nan Mo; Kim, Yong Kyu; Jang, Ja June [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1985-12-15

    The combination of the various diagnostic methods of palpable breast mass has improved the diagnostic accuracy. From September 1983 to August 1985 pathologically proven 85 patients with palpable breast masses examined with x-ray mammography, ultrasonography, penumomammography and aspiration cytology at Korea Cancer Center Hospital were analyzed. The diagnostic accuracies of each methods were 77.6% of mammogram, 74.1% of ultrasonogram, 90.5% of penumomammogram and 92.4% of aspiration cytology. Pneumomammograms was accomplished without difficulty or complication and depicted more clearly delineated mass with various pathognomonic findings; air-ductal pattern in fibroadenoma (90.4%) and cystosarcoma phylloides (100%), air-halo in fibrocystic disease (14.2%), fibroadenoma (100%), cystosarcoma phylloides (100%), air-cystogram in cystic type of fibrocystic disease (100%) and vaculoar pattern or irregular air collection without retained peripheral gas in carcinoma.

  9. Multiple Symmetric Lipomatosis: A Diagnostic Dilemma

    Directory of Open Access Journals (Sweden)

    Mladen Mimica

    2013-01-01

    Full Text Available Introduction. Multiple symmetric lipomatosis, or Madelung's disease, is a rare condition which is characterized with large symmetrical accumulation of noncapsulated fat tissue in upper arms, neck, and shoulder areas. The disease etiology is unknown, with the highest incidence in the Mediterranean region. Case Presentation. Here, we present the case of Madelung's disease with symmetric fat distribution throughout the neck and history of alcoholism. The patient was treated from several diseases associated with alcoholism and hospitalized several times, but the diagnosis of Madelung's disease was omitted. The thyroid gland disease was excluded, while enlargement of the neck adipose tissue was attributed to obesity. Conclusions. This study points out possible diagnostic mistakes when a physician is not aware of a differentiation diagnosis of symmetrically enlarged neck masses, especially in geographic regions with high incidence of this disease.

  10. Tumefactive multiple sclerosis: an uncommon diagnostic challenge.

    Science.gov (United States)

    Kaeser, Martha A; Scali, Frank; Lanzisera, Frank P; Bub, Glenn A; Kettner, Norman W

    2011-03-01

    This case report describes a rare presentation of multiple sclerosis (MS) that was initially diagnosed as a peripheral nerve lesion in the emergency department. A 30-year-old woman presented to a chiropractic teaching clinic with a complaint of a sudden right foot drop. Magnetic resonance imaging of the brain revealed a large mass in the left parietal lobe with additional white matter lesions. The mass and smaller lesions were consistent with a rare presentation of demyelinating disease, tumefactive MS. The patient was referred to a neurologist for further evaluation and treatment. Her short-term clinical course was punctuated by recurrent myospasms and neurologic deficits. Tumefactive MS may mimic the clinical and magnetic resonance imaging characteristics of glioma or a cerebral abscess. The clinical presentation, pathophysiology, differential diagnosis, role of diagnostic imaging, and treatment options of MS are described. This case report illustrates that the timely diagnosis and optimal treatment of MS require recognition of its varied, sometimes atypical, and often nonspecific clinical and imaging manifestations. Copyright © 2011 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

  11. Determination of hormonal combination for increased multiplication ...

    African Journals Online (AJOL)

    ACSS

    In Uganda, the use of tissue culture is a new technique in seed potato production, therefore, appropriate media composition for rapid multiplication of potato tissue culture plantlets has not been optimised. Thus, the objective of this study was to optimize hormonal combinations for increased multiplication of tissue culture.

  12. Bayesian modelling of multiple diagnostics at Wendelstein 7-X using the Minerva framework

    Science.gov (United States)

    Kwak, Sehyun; Svensson, Jakob; Bozhenkov, Sergey; Trimino Mora, Humberto; Hoefel, Udo; Pavone, Andrea; Krychowiak, Maciej; Langenberg, Andreas; Ghim, Young-Chul; W7-X Team Team

    2017-10-01

    Wendelstein 7-X (W7-X) is a large scale optimised stellarator designed for steady-state operation with fusion reactor relevant conditions. Consistent inference of physics parameters and their associated uncertainties requires the capability to handle the complexity of the entire system, including physics models of multiple diagnostics. A Bayesian model has been developed in the Minerva framework to infer electron temperature and density profiles from multiple diagnostics in a consistent way. Here, the physics models predict the data of multiple diagnostics in a joint Bayesian analysis. The electron temperature and density profiles are modelled by Gaussian processes with hyperparameters. Markov chain Monte Carlo methods explore the full posterior of electron temperature and density profiles as well as possible combinations of hyperparameters and calibration factors. This results in a profile inference with proper uncertainties reflecting both statistical error and the automatic calibration for diagnostics.

  13. [Diagnostics and surgery of combined lung echinococcosis].

    Science.gov (United States)

    Vafin, A Z; Diad'kov, A V; Aĭdemirov, A N; Malanka, M I; Abdokov, A D

    2013-01-01

    An analysis of surgical treatment of 162 patients with lung echinococcosis was made. The main group consisted of 74 patients with combined forms of echinococcosis of the lung and other organs. They were treated in clinic in the period of time since 1982 till 2011 years. The control group included of 88 patients with echinococcosis of lung and the patients were followed-up in the period of time since 1991 till 2000. Plasma technology was applied in all patients of control group. The patients from main group (25) were operated by using the conventional methods and 49 patients - with the application of plasma technology. An analysis shows a reliable reduction of the rate of postoperative complications after application of plasma technology in 4 times. The lethality significantly decreased in this group of patients.

  14. Ductal carcinoma in a multiple fibroadenoma: Diagnostic inaccuracies

    Directory of Open Access Journals (Sweden)

    Rao Shalinee

    2010-01-01

    Full Text Available We present the diagnostic inaccuracies encountered in a case of multiple fibroadenoma with malignant transformation. A 30-year-old lady presented with lump in the right breast of one month duration which on clinical examination, X-ray mammogram, sonomammogram were suggestive of multiple fibroadenomas. Fine needle aspiration cytology of the largest lump revealed features of malignancy and a core biopsy showed pleomorphic cells that could not be categorized. Due to the clinical, radiological and pathological diagnostic ambiguity, lumpectomy was performed and frozen section showed features of only conventional fibroadenoma. Representative bits on routine processing showed only features of fibroadenoma. Hence, complete submission of all lumps was done, which revealed fibroadenoma with invasive ductal carcinoma in one. Patient underwent modified radical mastectomy which showed multiple fibroadenomas, focal fibrocystic disease with a focus of residual invasive tumor and metastatic deposit in one axillary lymph node. This case report highlights the diagnostic challenges in detecting malignancy in fibroadenoma and a need for extensive tissue sampling in multiple fibroadenomas to detect the rare occurrence of carcinoma.

  15. Interobserver agreement for diagnostic MRI criteria in suspected multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Barkhof, F.; Waesberghe, J.H.T.M. van [Department of Radiology, Academic Hospital of the Vrije Universiteit, Amsterdam (Netherlands); Filippi, M.; Campi, A. [MS Biosignal Analysis Centre, Department of Neurology, Scientific Institute H San Raffaele, University of Milan (Italy); Miller, D.H. [NMR Research Group, Institute of Neurology, Queen Square, London (United Kingdom); Ader, H.J. [Department of Epidemiology and Biostatistics, Vrije Universiteit, Amsterdam (Netherlands)

    1999-05-01

    MRI is the paraclinical test most widely used to support the diagnosis of multiple sclerosis (MS). We evaluated interobserver agreement in applying diagnostic criteria to MRI obtained at first presentation. Five experienced observers scored 25 sets of images consisting of unenhanced T2- and gadolinium-enhanced T1-weighted images (approximately half the sets were normal). We scored frontal, parietal, temporal, occipital, infratentorial and basal ganglia lesions and the total number of lesions on T2-weighted images; periventricular, callosal, juxtacortical and ovoid lesions and those > 5 mm in maximum diameter; contrast-enhancing and hypointense lesions. Based on a combination of imaging findings patients were classified as compatible or not compatible with MS according to composite criteria. Observer concordance was characterised by weighted kappa values ({kappa}) and mean average difference to the median (MADM) scores. Using the raw scores, there was poor agreement for the total number of lesions on T2-weighted images, and for occipital, oval, juxtacortical and hypointense lesions. Moderate agreement was found for frontal, callosal, basal ganglia and large lesions on T2 weighting. Good agreement was attained for parietal, temporal, infratentorial and periventricular lesions. After dichotomisation according to accepted cut-off values, most criteria performed better, especially the number of lesions on T2-weighted images (P < 0.05). Good agreement was found for the criteria of Paty and Fazekas and moderate agreement for those of Barkhof. While experienced observers may not agree on the total number of lesions, they show quite good agreement for commonly used cut-off points and elements in the composite criteria. This validates the use of MRI in the diagnosis of MS, and the use of dichotomised and composite criteria. (orig.) With 2 tabs., 13 refs.

  16. Nonparametric predictive inference for combining diagnostic tests with parametric copula

    Science.gov (United States)

    Muhammad, Noryanti; Coolen, F. P. A.; Coolen-Maturi, T.

    2017-09-01

    Measuring the accuracy of diagnostic tests is crucial in many application areas including medicine and health care. The Receiver Operating Characteristic (ROC) curve is a popular statistical tool for describing the performance of diagnostic tests. The area under the ROC curve (AUC) is often used as a measure of the overall performance of the diagnostic test. In this paper, we interest in developing strategies for combining test results in order to increase the diagnostic accuracy. We introduce nonparametric predictive inference (NPI) for combining two diagnostic test results with considering dependence structure using parametric copula. NPI is a frequentist statistical framework for inference on a future observation based on past data observations. NPI uses lower and upper probabilities to quantify uncertainty and is based on only a few modelling assumptions. While copula is a well-known statistical concept for modelling dependence of random variables. A copula is a joint distribution function whose marginals are all uniformly distributed and it can be used to model the dependence separately from the marginal distributions. In this research, we estimate the copula density using a parametric method which is maximum likelihood estimator (MLE). We investigate the performance of this proposed method via data sets from the literature and discuss results to show how our method performs for different family of copulas. Finally, we briefly outline related challenges and opportunities for future research.

  17. DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF INTRATHECAL SYNTHESIS OF IMMUNOGLOBULIN FREE LIGHT CHAINS IN MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    V. D. Nazarov

    2015-01-01

    Full Text Available Increased intrathecal synthesis and oligoclonal banding of immunoglobulins (Ig in cerebrospinal fluid (CSF are major immunological findings in multiple sclerosis. Free light chains are fragments of Ig molecules that are produced in parallel to oligoclonal Ig, and their production reflects total Ig synthesis within central nervous system. Assessment of intrathecal kappaand lambda free light chain production within CNS compartment will help to improve diagnosis and prediction of outcomes in multiple sclerosis. Concentrations of kappa and lambda free light chains and clonality of immunoglobulin pattern synthesis were studied in paired CSF and serum samples of 151 patients, including 92 patients with multiple sclerosis, and 33 patients with clinically isolated syndrome which later was transformed into the definite multiple sclerosis. A control group consisted of 26 patients with other inflammatory diseases of central nervous system. Several Ig parameters have been determined in the patients, i.e., Ig clonality in CSF; concentrations of free light chains (both kappaand lambda- in CSF; as well as their indexes and ratios. It was established that synthesis of kappa free light chains were significantly elevated in patients with multiple sclerosis. Moreover, the amounts of free light Ig chains in patients with positive oligoclonality test were significantly higher than in cases without intrathecal oligoclonal synthesis. With respect to diagnostic significance, the kappa quotient proved the best available option for diagnosis of multiple sclerosis. Its combination with Ig oligoclonality assays caused a decrease in false-negative diagnostics by 42%. Diagnostic benefit of the kappa quotient could be also confirmed by the data of ROC analysis. Also concentration of lambda free light chains in cerebrospinal fluid showed a negative correlation with conversion terms of clinically isolated syndrome to evident multiple sclerosis. Therefore, the indexes of free Ig

  18. Multiple exostotic hypochondroplasia: Syndrome of combined hypochondroplasia and multiple exostoses

    Energy Technology Data Exchange (ETDEWEB)

    Dominguez, R.; Young, L.W.; Girdany, B.R.; Steele, M.W.

    1984-07-01

    This is a report of a family with major focus on the daughter who had short stature. The mother had hypochondroplasia and the father had multiple exostoses. The daughter's skeletal roentgenograms show features of both hypochondroplasia and multiple exostoses. The roentgenographic, clinical and genetic aspects of these skeletal dysplasias are reviewed and hypochrondroplasia is contrasted with achondroplasia. The genetic and counseling implications of the association of hypochondroplasia and multiple exostoses are discussed.

  19. Combining multiple classifiers for age classification

    CSIR Research Space (South Africa)

    Van Heerden, C

    2009-11-01

    Full Text Available The authors compare several different classifier combination methods on a single task, namely speaker age classification. This task is well suited to combination strategies, since significantly different feature classes are employed. Support vector...

  20. Determination of hormonal combination for increased multiplication ...

    African Journals Online (AJOL)

    Eight hormonal combinations were formulated and tested using a completely randomized design with three replicates in the tissue culture laboratory. Ten shoot tips from in-vitro raised plantlets were excised and transferred to each of these hormonal combinations. The effect of hormonal combinations was variety dependant ...

  1. Combined sensing platform for advanced diagnostics in exhaled mouse breath

    Science.gov (United States)

    Fortes, Paula R.; Wilk, Andreas; Seichter, Felicia; Cajlakovic, Merima; Koestler, Stefan; Ribitsch, Volker; Wachter, Ulrich; Vogt, Josef; Radermacher, Peter; Carter, Chance; Raimundo, Ivo M.; Mizaikoff, Boris

    2013-03-01

    Breath analysis is an attractive non-invasive strategy for early disease recognition or diagnosis, and for therapeutic progression monitoring, as quantitative compositional analysis of breath can be related to biomarker panels provided by a specific physiological condition invoked by e.g., pulmonary diseases, lung cancer, breast cancer, and others. As exhaled breath contains comprehensive information on e.g., the metabolic state, and since in particular volatile organic constituents (VOCs) in exhaled breath may be indicative of certain disease states, analytical techniques for advanced breath diagnostics should be capable of sufficient molecular discrimination and quantification of constituents at ppm-ppb - or even lower - concentration levels. While individual analytical techniques such as e.g., mid-infrared spectroscopy may provide access to a range of relevant molecules, some IR-inactive constituents require the combination of IR sensing schemes with orthogonal analytical tools for extended molecular coverage. Combining mid-infrared hollow waveguides (HWGs) with luminescence sensors (LS) appears particularly attractive, as these complementary analytical techniques allow to simultaneously analyze total CO2 (via luminescence), the 12CO2/13CO2 tracer-to-tracee (TTR) ratio (via IR), selected VOCs (via IR) and O2 (via luminescence) in exhaled breath, yet, establishing a single diagnostic platform as both sensors simultaneously interact with the same breath sample volume. In the present study, we take advantage of a particularly compact (shoebox-size) FTIR spectrometer combined with novel substrate-integrated hollow waveguide (iHWG) recently developed by our research team, and miniaturized fiberoptic luminescence sensors for establishing a multi-constituent breath analysis tool that is ideally compatible with mouse intensive care stations (MICU). Given the low tidal volume and flow of exhaled mouse breath, the TTR is usually determined after sample collection via gas

  2. DNA Diagnostics of Hereditary Hearing Loss: A Targeted Resequencing Approach Combined with a Mutation Classification System.

    Science.gov (United States)

    Sommen, Manou; Schrauwen, Isabelle; Vandeweyer, Geert; Boeckx, Nele; Corneveaux, Jason J; van den Ende, Jenneke; Boudewyns, An; De Leenheer, Els; Janssens, Sandra; Claes, Kathleen; Verstreken, Margriet; Strenzke, Nicola; Predöhl, Friederike; Wuyts, Wim; Mortier, Geert; Bitner-Glindzicz, Maria; Moser, Tobias; Coucke, Paul; Huentelman, Matthew J; Van Camp, Guy

    2016-08-01

    Although there are nearly 100 different causative genes identified for nonsyndromic hearing loss (NSHL), Sanger sequencing-based DNA diagnostics usually only analyses three, namely, GJB2, SLC26A4, and OTOF. As this is seen as inadequate, there is a need for high-throughput diagnostic methods to detect disease-causing variations, including single-nucleotide variations (SNVs), insertions/deletions (Indels), and copy-number variations (CNVs). In this study, a targeted resequencing panel for hearing loss was developed including 79 genes for NSHL and selected forms of syndromic hearing loss. One-hundred thirty one presumed autosomal-recessive NSHL (arNSHL) patients of Western-European ethnicity were analyzed for SNVs, Indels, and CNVs. In addition, we established a straightforward variant classification system to deal with the large number of variants encountered. We estimate that combining prescreening of GJB2 with our panel leads to a diagnosis in 25%-30% of patients. Our data show that after GJB2, the most commonly mutated genes in a Western-European population are TMC1, MYO15A, and MYO7A (3.1%). CNV analysis resulted in the identification of causative variants in two patients in OTOA and STRC. One of the major challenges for diagnostic gene panels is assigning pathogenicity for variants. A collaborative database collecting all identified variants from multiple centers could be a valuable resource for hearing loss diagnostics. © 2016 WILEY PERIODICALS, INC.

  3. Measuring and combining multiple diagnostic and prognostic sepsis biomarkers

    DEFF Research Database (Denmark)

    Kofoed, Kristian

    2008-01-01

    of sepsis is of great importance for choice of treatment, level of monitoring and prognosis. In this biomarkers could be a significant aid, and thus the search for and application of "new" sepsis biomarkers is of great importance. The thesis reviews the definitions and the epidemiology, and gives...... an overview of the immunology of sepsis with emphasis on the suggested roles of the soluble fractions of triggering receptor expressed on myeloide cells-1 (sTREM-1), urokinase-type plasminogen activator receptor (suPAR), and the cytokine macrophage migration inhibitory factor (MIF). The Luminex technology...... is described, it is explained how a multiplex assay is developed and validated, and based on our experience and on the literature the advantages and shortcomings of the method are discussed. In the last part the results of the two clinical studies on 161 patients suspected of sepsis are put into the context...

  4. Measuring and combining multiple diagnostic and prognostic sepsis biomarkers

    DEFF Research Database (Denmark)

    Kofoed, Kristian

    2008-01-01

    of sepsis is of great importance for choice of treatment, level of monitoring and prognosis. In this biomarkers could be a significant aid, and thus the search for and application of "new" sepsis biomarkers is of great importance. The thesis reviews the definitions and the epidemiology, and gives...... an overview of the immunology of sepsis with emphasis on the suggested roles of the soluble fractions of triggering receptor expressed on myeloide cells-1 (sTREM-1), urokinase-type plasminogen activator receptor (suPAR), and the cytokine macrophage migration inhibitory factor (MIF). The Luminex technology...

  5. Combining the IADPSG criteria with the WHO diagnostic criteria for ...

    African Journals Online (AJOL)

    Background: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes, yet there are no universally accepted ... and World Health Organization's (WHO) diagnostic criteria are commonly used criteria, although clinical outcome data .... GDM, hypertensive disorder, maternal age, maternal obesity,.

  6. DIAGNOSTICS OF INDUCTION MOTOR ROTOR COMBINED DEFECTS WITH AN INDUCTION METHOD

    Directory of Open Access Journals (Sweden)

    Y.N. Vas’kovsky

    2013-06-01

    Full Text Available A diagnostics methodology for combined defects of induction motor rotors is introduced, the defects considered being simultaneous damage of rods, cage rings, and the rotor active steel. Diagnostic features and recommendations on the rotor combined defects identification are formulated.

  7. Combining the IADPSG criteria with the WHO diagnostic criteria for ...

    African Journals Online (AJOL)

    Odds ratio (OR) =13.1, 95% confidence interval (CI) = 3.4–50.6] compared to the GDMIADPSG women (OR = 5.3, 95% CI 1.5–18.9). Macrosomia or at least one adverse outcome were more likely in GDM patients who met the diagnostic criteria by ...

  8. Diagnostic accuracy for major depression in multiple sclerosis using self-report questionnaires

    OpenAIRE

    Fischer, Anja; Fischer, Marcus; Nicholls, Robert A; Lau, Stephanie; Poettgen, Jana; Patas, Kostas; Heesen, Christoph; Gold, Stefan M

    2015-01-01

    Objective Multiple sclerosis and major depressive disorder frequently co-occur but depression often remains undiagnosed in this population. Self-rated depression questionnaires are a good option where clinician-based standardized diagnostics are not feasible. However, there is a paucity of data on diagnostic accuracy of self-report measures for depression in multiple sclerosis (MS). Moreover, head-to-head comparisons of common questionnaires are largely lacking. This could be particularly rel...

  9. Diagnostic Peptide Discovery: Prioritization of Pathogen Diagnostic Markers Using Multiple Features

    Science.gov (United States)

    Carmona, Santiago J.; Sartor, Paula A.; Leguizamón, María S.; Campetella, Oscar E.; Agüero, Fernán

    2012-01-01

    The availability of complete pathogen genomes has renewed interest in the development of diagnostics for infectious diseases. Synthetic peptide microarrays provide a rapid, high-throughput platform for immunological testing of potential B-cell epitopes. However, their current capacity prevent the experimental screening of complete “peptidomes”. Therefore, computational approaches for prediction and/or prioritization of diagnostically relevant peptides are required. In this work we describe a computational method to assess a defined set of molecular properties for each potential diagnostic target in a reference genome. Properties such as sub-cellular localization or expression level were evaluated for the whole protein. At a higher resolution (short peptides), we assessed a set of local properties, such as repetitive motifs, disorder (structured vs natively unstructured regions), trans-membrane spans, genetic polymorphisms (conserved vs. divergent regions), predicted B-cell epitopes, and sequence similarity against human proteins and other potential cross-reacting species (e.g. other pathogens endemic in overlapping geographical locations). A scoring function based on these different features was developed, and used to rank all peptides from a large eukaryotic pathogen proteome. We applied this method to the identification of candidate diagnostic peptides in the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. We measured the performance of the method by analyzing the enrichment of validated antigens in the high-scoring top of the ranking. Based on this measure, our integrative method outperformed alternative prioritizations based on individual properties (such as B-cell epitope predictors alone). Using this method we ranked 10 million 12-mer overlapping peptides derived from the complete T. cruzi proteome. Experimental screening of 190 high-scoring peptides allowed the identification of 37 novel epitopes with diagnostic potential, while none

  10. Diagnostic peptide discovery: prioritization of pathogen diagnostic markers using multiple features.

    Directory of Open Access Journals (Sweden)

    Santiago J Carmona

    Full Text Available The availability of complete pathogen genomes has renewed interest in the development of diagnostics for infectious diseases. Synthetic peptide microarrays provide a rapid, high-throughput platform for immunological testing of potential B-cell epitopes. However, their current capacity prevent the experimental screening of complete "peptidomes". Therefore, computational approaches for prediction and/or prioritization of diagnostically relevant peptides are required. In this work we describe a computational method to assess a defined set of molecular properties for each potential diagnostic target in a reference genome. Properties such as sub-cellular localization or expression level were evaluated for the whole protein. At a higher resolution (short peptides, we assessed a set of local properties, such as repetitive motifs, disorder (structured vs natively unstructured regions, trans-membrane spans, genetic polymorphisms (conserved vs. divergent regions, predicted B-cell epitopes, and sequence similarity against human proteins and other potential cross-reacting species (e.g. other pathogens endemic in overlapping geographical locations. A scoring function based on these different features was developed, and used to rank all peptides from a large eukaryotic pathogen proteome. We applied this method to the identification of candidate diagnostic peptides in the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. We measured the performance of the method by analyzing the enrichment of validated antigens in the high-scoring top of the ranking. Based on this measure, our integrative method outperformed alternative prioritizations based on individual properties (such as B-cell epitope predictors alone. Using this method we ranked [Formula: see text]10 million 12-mer overlapping peptides derived from the complete T. cruzi proteome. Experimental screening of 190 high-scoring peptides allowed the identification of 37 novel epitopes with

  11. Combining Scores in Multiple-Criteria Assessment Systems: The Impact of Combination Rule

    Science.gov (United States)

    McBee, Matthew T.; Peters, Scott J.; Waterman, Craig

    2014-01-01

    Best practice in gifted and talented identification procedures involves making decisions on the basis of multiple measures. However, very little research has investigated the impact of different methods of combining multiple measures. This article examines the consequences of the conjunctive ("and"), disjunctive/complementary…

  12. Combining multiple influence strategies to increase consumer compliance

    NARCIS (Netherlands)

    Kaptein, M.C.; Duplinsky, S.

    2013-01-01

    In this paper, we investigate the effects and implications of utilising multiple social influence strategies simultaneously to endorse a single product or call to action. In three, studies we show that combinations of social influence strategies do not increase compliance - this is contrary to

  13. [Significant changes in diagnostic and therapeutic procedures in smoldering multiple myeloma].

    Science.gov (United States)

    Jurczyszyn, Artur; Olszewska-Szopa, Magdalena; Skotnicki, Aleksander B

    2015-01-01

    Smoldering multiple myeloma (SMM) is a precursor disease of multiple myeloma (MM) with an average annual risk of progression to MM of 10%. Several prognostic factors have been identified and combined in models to discriminate patient groups with different outcomes. These factors include size of the M-protein, plasma cell (PC) infiltration in the bone marrow (BM), serum free light-chain ratio, immunoparesis and percentage of aberrant BMPCs on flow cytometry or the presence of focal lesions on magnetic resonance imaging. The current standard of care has been to initiate treatment with progression to symptomatic MM. Current approaches aim at identifying patients with an ultra-high risk of progression (≥ 80% within the first 2 years) who are considered as 'early myeloma' patients requiring therapy. A recent trial on high-risk SMM patients, comparing early treatment with lenalidomide plus dexamethasone (Rd) versus observation, reported a benefit with respect to time to progression and survival for Rd-treated patients. Therefore, in 2014, the International Myeloma Working Group (IMWG) revised the diagnostic criteria and proposed to treat patients with ultra-high risk SMM as symptomatic MM. Promising markers for further studies may be high levels of circulating and high proliferative rate of PCs, abnormal PC phenotype with > 95% plus immunoparesis, evolving SMM, specific cytogenetic subtypes, genomic and additional biomarkers; all being acknowledged by the IMWG be added to the diagnostic criteria in the future, if any proves to be associated with a risk of progression of SMM to MM of at least 80% within 2 years.

  14. The combination of psoriasis and secondary syphilis. Role of dermatoscopy in differential diagnostics

    Directory of Open Access Journals (Sweden)

    Sherstobitova K.Yu.

    2015-09-01

    Full Text Available A clinical case of the combination of psoriasis and secondary syphilis is presented. The problem of differential diagnostics of the clinical manifestations of syphilis and psoriasis, including the dermatoscopy usage are considered.

  15. Using Combined Diagnostic Test Results to Hindcast Trends of Infection from Cross-Sectional Data.

    Directory of Open Access Journals (Sweden)

    Gustaf Rydevik

    2016-07-01

    Full Text Available Infectious disease surveillance is key to limiting the consequences from infectious pathogens and maintaining animal and public health. Following the detection of a disease outbreak, a response in proportion to the severity of the outbreak is required. It is thus critical to obtain accurate information concerning the origin of the outbreak and its forward trajectory. However, there is often a lack of situational awareness that may lead to over- or under-reaction. There is a widening range of tests available for detecting pathogens, with typically different temporal characteristics, e.g. in terms of when peak test response occurs relative to time of exposure. We have developed a statistical framework that combines response level data from multiple diagnostic tests and is able to 'hindcast' (infer the historical trend of an infectious disease epidemic. Assuming diagnostic test data from a cross-sectional sample of individuals infected with a pathogen during an outbreak, we use a Bayesian Markov Chain Monte Carlo (MCMC approach to estimate time of exposure, and the overall epidemic trend in the population prior to the time of sampling. We evaluate the performance of this statistical framework on simulated data from epidemic trend curves and show that we can recover the parameter values of those trends. We also apply the framework to epidemic trend curves taken from two historical outbreaks: a bluetongue outbreak in cattle, and a whooping cough outbreak in humans. Together, these results show that hindcasting can estimate the time since infection for individuals and provide accurate estimates of epidemic trends, and can be used to distinguish whether an outbreak is increasing or past its peak. We conclude that if temporal characteristics of diagnostics are known, it is possible to recover epidemic trends of both human and animal pathogens from cross-sectional data collected at a single point in time.

  16. Familial combined hyperlipidemia : metabolic features and new diagnostic criteria

    NARCIS (Netherlands)

    Veerkamp, M.J.

    2004-01-01

    Familial Combined Hyperlipidemia (FCH) is the most common inherited hyperlipidemia in humans with an increased risk of cardiovascular disease (CVD). Therefore, it is of great importance to identify and treat subjects with FCH appropriately. The exact pathophysiology of FCH is still unknown, also the

  17. Credibility of the combined test in prenatal diagnostics

    Directory of Open Access Journals (Sweden)

    Lončar Dragan

    2011-01-01

    Full Text Available Congenital anomalies are the cause of perinatal death in 20-25% of the cases, while 3% of children are born with malformation of varying size. The objective of this study was to examine the predictive value and define the credibility ratio of the combined test results. Of 317 examined pregnant women, we had sixteen (5.05% with the result of pathological karyotype after amniocentesis including: nine (2.84% with fetal numerical aberrations and seven (2.21% with fetal structural aberrations. While determining the ultrasonographic parameters of the combined test we used the standards of the Fetal Medicine Foundation. We carried out the quantitative settings of free β-HCG and PAPP-A from vein blood of patients by applying commercial tests of firm DPC-USA. Tests were based on the analytical immunochemiluminescence assay and were realized by using the automated analyzer IMMULITE 2000. Manufacturer of the analyzer is also the firm DPC-USA. Sensitivity of the test is 94%, and specificity is 99%. Positive likelihood ratio [likelihood ratio test (LR+] is 94.00, a negative likelihood ratio is [likelihood ratio test (LR-] 12:06. Pretest probability that pregnant women carries fetus with chromosomal abnormality is 1:250 or 0004. Posttest odds after the combined test to discover this abnormality is 0.3760, and probability of the same case is 0.2732 if it happens that the test result is positive. The result of our study confirms the justification of combined test usage in routine clinical practice, since the posttest odds rate in the case of a positive screening increases several times over (almost 90 times, the probability of detecting a chromosomal abnormality was about 70 times. Combined screening test if used methodologically correct, has a high predictive value in detecting fetal congenital anomalies.

  18. Radiological diagnostics of multiple myeloma; Radiologische Diagnostik des multiplen Myeloms

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    D' Anastasi, M.; Grandl, S.; Reiser, M.F.; Baur-Melnyk, A. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany)

    2014-06-15

    Robust and reliable imaging methods are required to estimate the skeletal tumor load in multiple myeloma, as well as for the diagnosis of extraskeletal manifestations. Imaging also plays an essential role in the assessment of fracture risk and of vertebral fractures. The conventional skeletal survey has been the gold standard in the imaging of multiple myeloma for many years. Other modalities which have been investigated and are in use are whole-body computed tomography (WBCT), 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET-CT) and whole-body magnetic resonance imaging (WBMRI). These techniques are able to depict both mineralized bone and the bone marrow with a high sensitivity for myeloma lesions. Several studies have shown that cross-sectional imaging is superior to the skeletal survey in the detection of myeloma lesions and WBMRI has been shown to be significantly more sensitive than WBCT for the detection of focal myeloma lesions as well as for diffuse infiltration. The FDG PET-CT technique has a sensitivity comparable to WBMRI. Due to the higher sensitivity in the detection of myeloma lesions WBCT and WBMRI should replace the skeletal survey. A WBCT should be performed if there is suspicion of multiple myeloma. If no focal lesions are found WBMRI or at least MRI of the spine and pelvis should be additionally performed if available. If WBMRI has been initially performed and focal lesions are present, an additional WBCT may be performed to assess the extent of bone destruction and fracture risk. In cases of monoclonal gammopathy of undetermined significance (MGUS), solitary and smoldering myeloma, a WBMRI, if available, should be performed in addition to WBCT. (orig.) [German] Die Aufgabe der bildgebenden Diagnostik beim multiplen Myelom (MM) ist die zuverlaessige Erfassung der Tumorlast im Skelett sowie auch der extraskelettalen Manifestationen und der assoziierten Komplikationen (z. B. Wirbelkoerperfrakturen, Frakturgefahr

  19. Diagnostic potential of plasma carboxymethyllysine and carboxyethyllysine in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Weinstock-Guttmann Bianca

    2010-10-01

    Full Text Available Abstract Background This study compared the level of advanced glycation end products (AGEs, N-(Carboxymethyllysine (CML and N-(Carboxyethyllysine (CEL, in patients with multiple sclerosis (MS and healthy controls (HCs, correlating these markers with clinical indicators of MS disease severity. Methods CML and CEL plasma levels were analyzed in 99 MS patients and 43 HCs by tandem mass spectrometry (LC/MS/MS. Patients were stratified based on drug modifying therapies (DMTs including interferon beta, glatiramer acetate and natalizumab. Results The level of plasma CEL, but not CML, was significantly higher in DMT-naïve MS patients when compared to HCs (P Conclusion Our results suggest that AGEs in general and CEL in particular could be useful biomarkers in MS clinical practice. Longitudinal studies are warranted to determine any causal relationship between changes in plasma level of AGEs and MS disease pathology. These studies will pave the way for use of AGE inhibitors and AGE-breaking agents as new therapeutic modalities in MS.

  20. Combining results of multiple search engines in proteomics.

    Science.gov (United States)

    Shteynberg, David; Nesvizhskii, Alexey I; Moritz, Robert L; Deutsch, Eric W

    2013-09-01

    A crucial component of the analysis of shotgun proteomics datasets is the search engine, an algorithm that attempts to identify the peptide sequence from the parent molecular ion that produced each fragment ion spectrum in the dataset. There are many different search engines, both commercial and open source, each employing a somewhat different technique for spectrum identification. The set of high-scoring peptide-spectrum matches for a defined set of input spectra differs markedly among the various search engine results; individual engines each provide unique correct identifications among a core set of correlative identifications. This has led to the approach of combining the results from multiple search engines to achieve improved analysis of each dataset. Here we review the techniques and available software for combining the results of multiple search engines and briefly compare the relative performance of these techniques.

  1. Combining Results of Multiple Search Engines in Proteomics*

    Science.gov (United States)

    Shteynberg, David; Nesvizhskii, Alexey I.; Moritz, Robert L.; Deutsch, Eric W.

    2013-01-01

    A crucial component of the analysis of shotgun proteomics datasets is the search engine, an algorithm that attempts to identify the peptide sequence from the parent molecular ion that produced each fragment ion spectrum in the dataset. There are many different search engines, both commercial and open source, each employing a somewhat different technique for spectrum identification. The set of high-scoring peptide-spectrum matches for a defined set of input spectra differs markedly among the various search engine results; individual engines each provide unique correct identifications among a core set of correlative identifications. This has led to the approach of combining the results from multiple search engines to achieve improved analysis of each dataset. Here we review the techniques and available software for combining the results of multiple search engines and briefly compare the relative performance of these techniques. PMID:23720762

  2. Combined pulse-oximeter-NIRS system for biotissue diagnostics

    Science.gov (United States)

    Hovhannisyan, Vladimir A.

    2005-08-01

    Multi-wavelength (670, 805, 848 and 905 nm), multi-detector device for non-invasive measurement of biochemical components concentration in human or animal tissues, combining the methods of conventional pulse-oximetry and near infrared spectroscopy, is developed. The portable and clinically applicable system allows to measure heart pulse rate, oxygen saturation of arterial hemoglobin (pulse-oximetry method) and local absolute concentration of oxyhemoglobin, deoxyhemoglobin and oxidized cytochrome aa3 or other IR absorbed compounds (NIRS method). The system can be applied in monitoring of oxygen availability and utilization by the brain in neonatal and adults, neuro- traumatology, intensive care medicine, transplantation and plastic surgery, in sport, high-altitude and aviation medicine.

  3. An approach for combining multiple descriptors for image classification

    Science.gov (United States)

    Tran, Duc Toan; Jansen, Bart; Deklerck, Rudi; Debeir, Olivier

    2015-02-01

    Recently, efficient image descriptors have shown promise for image classification tasks. Moreover, methods based on the combination of multiple image features provide better performance compared to methods based on a single feature. This work presents a simple and efficient approach for combining multiple image descriptors. We first employ a Naive-Bayes Nearest-Neighbor scheme to evaluate four widely used descriptors. For all features, "Image-to-Class" distances are directly computed without descriptor quantization. Since distances measured by different metrics can be of different nature and they may not be on the same numerical scale, a normalization step is essential to transform these distances into a common domain prior to combining them. Our experiments conducted on a challenging database indicate that z-score normalization followed by a simple sum of distances fusion technique can significantly improve the performance compared to applications in which individual features are used. It was also observed that our experimental results on the Caltech 101 dataset outperform other previous results.

  4. The assessment of changes in multiple cystic encephalomalacia with diagnostic ultrasound.

    Science.gov (United States)

    Stannard, M W; Jimenez, J F

    1983-01-01

    Multiple cystic encephalomalacia causes irregular cavities in both hemispheres which often enlarge causing shift of midline structures and increase in head size. Diagnostic ultrasound is the ideal method assessing the size of cysts, the need for cyst shunts and the response to treatment.

  5. Automatic plankton image classification combining multiple view features via multiple kernel learning.

    Science.gov (United States)

    Zheng, Haiyong; Wang, Ruchen; Yu, Zhibin; Wang, Nan; Gu, Zhaorui; Zheng, Bing

    2017-12-28

    Plankton, including phytoplankton and zooplankton, are the main source of food for organisms in the ocean and form the base of marine food chain. As the fundamental components of marine ecosystems, plankton is very sensitive to environment changes, and the study of plankton abundance and distribution is crucial, in order to understand environment changes and protect marine ecosystems. This study was carried out to develop an extensive applicable plankton classification system with high accuracy for the increasing number of various imaging devices. Literature shows that most plankton image classification systems were limited to only one specific imaging device and a relatively narrow taxonomic scope. The real practical system for automatic plankton classification is even non-existent and this study is partly to fill this gap. Inspired by the analysis of literature and development of technology, we focused on the requirements of practical application and proposed an automatic system for plankton image classification combining multiple view features via multiple kernel learning (MKL). For one thing, in order to describe the biomorphic characteristics of plankton more completely and comprehensively, we combined general features with robust features, especially by adding features like Inner-Distance Shape Context for morphological representation. For another, we divided all the features into different types from multiple views and feed them to multiple classifiers instead of only one by combining different kernel matrices computed from different types of features optimally via multiple kernel learning. Moreover, we also applied feature selection method to choose the optimal feature subsets from redundant features for satisfying different datasets from different imaging devices. We implemented our proposed classification system on three different datasets across more than 20 categories from phytoplankton to zooplankton. The experimental results validated that our system

  6. Combining Results From Multiple Evaluations of the Same Measurand.

    Science.gov (United States)

    Kessel, Rüdiger; Kacker, Raghu N; Sommer, Klaus-Dieter

    2011-01-01

    According to the Guide to the Expression of Uncertainty in Measurement (GUM), a result of measurement consists of a measured value together with its associated standard uncertainty. The measured value and the standard uncertainty are interpreted as the expected value and the standard deviation of a state-of-knowledge probability distribution attributed to the measurand. We discuss the term metrological compatibility introduced by the International Vocabulary of Metrology, third edition (VIM3) for lack of significant differences between two or more results of measurement for the same measurand. Sometimes a combined result of measurement from multiple evaluations of the same measurand is needed. We propose an approach for determining a combined result which is metrologically compatible with the contributing results.

  7. Tuning Cell and Tissue Development by Combining Multiple Mechanical Signals.

    Science.gov (United States)

    Sinha, Ravi; Verdonschot, Nico; Koopman, Bart; Rouwkema, Jeroen

    2017-10-01

    Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.

  8. 78 FR 21128 - Molecular Diagnostic Instruments With Combined Functions; Draft Guidance for Industry and Food...

    Science.gov (United States)

    2013-04-09

    ... HUMAN SERVICES Food and Drug Administration Molecular Diagnostic Instruments With Combined Functions; Draft Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the...

  9. The Added Value of the Combined Use of the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule: Diagnostic Validity in a Clinical Swedish Sample of Toddlers and Young Preschoolers

    Science.gov (United States)

    Zander, Eric; Sturm, Harald; Bölte, Sven

    2015-01-01

    The diagnostic validity of the new research algorithms of the Autism Diagnostic Interview-Revised and the revised algorithms of the Autism Diagnostic Observation Schedule was examined in a clinical sample of children aged 18-47 months. Validity was determined for each instrument separately and their combination against a clinical consensus…

  10. The Differential Diagnosis of Multiple Sclerosis Using Convex Combination of Infinite Kernels.

    Science.gov (United States)

    Karaca, Yeliz; Zhang, Yu-Dong; Cattani, Carlo; Ayan, Ugur

    2017-01-01

    Our purpose is to develop a clinical decision support system to classify the patients' diagnostics based on features gathered from Magnetic Resonance Imaging (MRI) and Expanded Disability Status Scale (EDSS). We studied 120 patients and 19 healthy individuals (not afflicted with MS) have been studied for this study. Healthy individuals in the control group do not have any complaint or drug use history. For the kernel trick, efficient performance in non-linear classification, the Convex Combination of Infinite Kernels model was developed to measure the health status of patients based on features gathered from MRI and EDSS. Our calculations show that our proposed model classifies the multiple sclerosis (MS) diagnosis level with better accuracy than single kernel, artificial neural network and other machine learning methods, and it can also be used as a decision support system for identifying MS health status of patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Diagnostic delay in narcolepsy type 1: combining the patients' and the doctors' perspectives.

    Science.gov (United States)

    Taddei, Raquel N; Werth, Esther; Poryazova, Rositsa; Baumann, Christian R; Valko, Philipp O

    2016-12-01

    Narcolepsy type 1 is a neurological disorder characterized by a unique syndrome, including the pathognomonic symptom of cataplexy. The diagnosis can be confirmed by objective measures, such as typical findings in the multiple sleep latency test, reduced or undetectable levels of orexin (hypocretin) in the cerebrospinal fluid, and linkage to a specific HLA haplotype. Nevertheless, the mean time that elapses from symptom onset to the correct diagnosis ranges between 10 and 20 years, and the causes and correlates of this delay are poorly understood. Diagnostic delay was assessed on 52 well-defined patients with narcolepsy type 1, evaluating clinical, electrophysiological and neurochemical parameters and the results of a 41-item questionnaire developed to obtain the patients' perspective on various aspects of the diagnostic process. The mean time gap between disease onset and first medical consultation was 3.2 ± 5.1 years; the mean diagnostic delay was 8.9 ± 11.0 years. Prior to correct diagnosis, patients received a wide variety of misdiagnoses. The self-ratings of the patients revealed that the undiagnosed symptoms caused high levels of anxiety and unjustified criticism by family, friends and employers. Multiple regression analysis identified higher cerebrospinal fluid orexin levels (β = 0.311, P = 0.01), and a longer interval between the onset of excessive daytime sleepiness and cataplexy (β = 0.368, P = 0.002) as independent associates of longer diagnostic delay. The diagnostic delay decreased over the last decades (β = -0.672, P narcolepsy type 1 is very common, associated with many adverse consequences, and requires educational efforts to improve awareness on narcolepsy among healthcare providers and the general population. © 2016 European Sleep Research Society.

  12. Magnetic Resonance Imaging of Intracranial Hypotension: Diagnostic Value of Combined Qualitative Signs and Quantitative Metrics.

    Science.gov (United States)

    Aslan, Kerim; Gunbey, Hediye Pinar; Tomak, Leman; Ozmen, Zafer; Incesu, Lutfi

    2017-07-13

    The aim of this study was to investigate whether the use of combination quantitative metrics (mamillopontine distance [MPD], pontomesencephalic angle, and mesencephalon anterior-posterior/medial-lateral diameter ratios) with qualitative signs (dural enhancement, subdural collections/hematoma, venous engorgement, pituitary gland enlargements, and tonsillar herniations) provides a more accurate diagnosis of intracranial hypotension (IH). The quantitative metrics and qualitative signs of 34 patients and 34 control subjects were assessed by 2 independent observers. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of quantitative metrics and qualitative signs, and for the diagnosis of IH, optimum cutoff values of quantitative metrics were found with ROC analysis. Combined ROC curve was measured for the quantitative metrics, and qualitative signs combinations in determining diagnostic accuracy and sensitivity, specificity, and positive and negative predictive values were found, and the best model combination was formed. Whereas MPD and pontomesencephalic angle were significantly lower in patients with IH when compared with the control group (P signs, the highest individual distinctive power was dural enhancement with area under the ROC curve (AUC) of 0.838. For quantitative metrics, the highest individual distinctive power was MPD with AUC of 0.947. The best accuracy in the diagnosis of IH was obtained by combination of dural enhancement, venous engorgement, and MPD with an AUC of 1.00. This study showed that the combined use of dural enhancement, venous engorgement, and MPD had diagnostic accuracy of 100 % for the diagnosis of IH. Therefore, a more accurate IH diagnosis can be provided with combination of quantitative metrics with qualitative signs.

  13. Combination of interferometry and thermography data for cultural heritage structural diagnostic research

    Science.gov (United States)

    Tornari, Vivi; Andrianakis, Michalis; Hatzigiannakis, Kostas; Kosma, Kiki; Detalle, Vincent; Giovanacci, David

    2017-07-01

    The demand for non destructive and non invasive structural diagnostic techniques able to perform on field remote structural evaluation of historical structures and works of art it faces an increased demand. The techniques must have some basic important characteristics The non destructivity, accuracy, repeatability, non physical contact, portability, resolution, broad range of applicability depending on the type of artwork and the question at hand, are all among the important requirements underlying the requirement for on-field structural diagnostics. In this respect there are two known techniques that have been developed at full to provide a suited structural diagnostic application in artwork conservation. The systems presented here but discussed in detail elsewhere are stimulated infrared thermography (SIRT) and digital holographic speckle pattern interferometry (DHSPI) the prior can be found n market at commercial devise level while the latter is at laboratory prototype level. The two systems are being exploited for their complimentary advantages and in this paper are used in combined testing on art related targets according to the above criteria to confirm the enhanced diagnostic information that their complimentary use provides. Results confirm the effectiveness of each technique alone and the combination of data of both techniques in the conservation field. Each system is first briefly described and examples are given with the aim to present the suitability and appropriateness for use in structural documentation analysis and reports. The experimental work is in laboratory work-in-progress focusing on the hybriding of data synthesis.

  14. Diagnostic Value of the Methylation of Multiple Gene Promoters in Serum in Hepatitis B Virus-Related Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Xueyan Dong

    2017-01-01

    Full Text Available This study sought to evaluate the diagnostic value of the methylation of multiple gene promoters in serum in hepatitis B virus- (HBV- related hepatocellular carcinoma (HCC. A total of 343 participants were enrolled, including 98 patients with HCC, 75 patients with liver cirrhosis (LC, 90 patients with chronic hepatitis B (CHB, and 80 healthy individuals. RASSF1A, APC, BVES, TIMP3, GSTP1, and HOXA9 were selected as the candidate genes. The MethyLight method was used to assay promoter methylation statuses. The diagnostic performances of markers were assessed by constructing receiver operating characteristic (ROC curves. The prevalences of methylation for RASSF1A, APC, BVES, HOXA9, GSTP1, and TIMP3 were 52.04%, 36.73%, 29.59%, 20.41%, 17.35%, and 11.22%, respectively. APC methylation completely overlapped with RASSF1A methylation. The area under the curve (AUC for RASSF1A methylation (0.718 was better than the corresponding AUC for AFP (0.609 in distinguishing HCC from CHB. When RASSF1A, BVES, HOXA9, and AFP were combined, the AUC was 0.852 (95% CI = 0.796–0.908, P=0.028, and the sensitivity and specificity were 83.7% and 78.9%, respectively. In conclusion, an assay that combines methylation of the RASSF1A, BVES, and HOXA9 gene promoters in serum and AFP could significantly improve HBV-related HCC diagnoses.

  15. Diagnostic accuracy for major depression in multiple sclerosis using self-report questionnaires.

    Science.gov (United States)

    Fischer, Anja; Fischer, Marcus; Nicholls, Robert A; Lau, Stephanie; Poettgen, Jana; Patas, Kostas; Heesen, Christoph; Gold, Stefan M

    2015-09-01

    Multiple sclerosis and major depressive disorder frequently co-occur but depression often remains undiagnosed in this population. Self-rated depression questionnaires are a good option where clinician-based standardized diagnostics are not feasible. However, there is a paucity of data on diagnostic accuracy of self-report measures for depression in multiple sclerosis (MS). Moreover, head-to-head comparisons of common questionnaires are largely lacking. This could be particularly relevant for high-risk patients with depressive symptoms. Here, we compare the diagnostic accuracy of the Beck Depression Inventory (BDI) and 30-item version of the Inventory of Depressive Symptomatology Self-Rated (IDS-SR30) for major depressive disorder (MSS) against diagnosis by a structured clinical interview. Patients reporting depressive symptoms completed the BDI, the IDS-SR30 and underwent diagnostic assessment (Mini International Neuropsychiatric Interview, M.I.N.I.). Receiver-Operating Characteristic analyses were performed, providing error estimates and false-positive/negative rates of suggested thresholds. Data from n = 31 MS patients were available. BDI and IDS-SR30 total score were significantly correlated (r = 0.82). The IDS-SR30total score, cognitive subscore, and BDI showed excellent to good accuracy (area under the curve (AUC) 0.86, 0.91, and 0.85, respectively). Both the IDS-SR30 and the BDI are useful to quantify depressive symptoms showing good sensitivity and specificity. The IDS-SR30 cognitive subscale may be useful as a screening tool and to quantify affective/cognitive depressive symptomatology.

  16. Synergy Effect of Combining Fluorescence and Mid Infrared Fiber Spectroscopy for Kidney Tumor Diagnostics

    Directory of Open Access Journals (Sweden)

    Andrey Bogomolov

    2017-11-01

    Full Text Available Matching pairs of tumor and non-tumor kidney tissue samples of four patients were investigated ex vivo using a combination of two methods, attenuated total reflection mid infrared spectroscopy and fluorescence spectroscopy, through respectively prepared and adjusted fiber probes. In order to increase the data information content, the measurements on tissue samples in both methods were performed in the same 31 preselected positions. Multivariate data analysis revealed a synergic effect of combining the two methods for the diagnostics of kidney tumor compared to individual techniques.

  17. Survey of diagnostic and treatment practices for multiple sclerosis in Europe

    DEFF Research Database (Denmark)

    Fernández, O; Delvecchio, M; Edan, G

    2017-01-01

    BACKGROUND AND PURPOSE: Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice....... METHODS: A steering committee of MS neurologists used a modified Delphi process to develop case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case-based questions were developed for radiologically isolated syndrome (RIS), clinically isolated...

  18. Diagnostic performance of combined cardiac MRI for detection of coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Andrade Fernandes de Mello, Ricardo, E-mail: ricardoafmello@gmail.com [Hospital de Clinicas de Niteroi - HCN, Niteroi, RJ (Brazil); Radiology Department, Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ (Brazil); Universidade Federal do Espirito Santo - UFES, Vitroria, ES (Brazil); Nacif, Marcelo Souto, E-mail: msnacif@gmail.com [Hospital de Clinicas de Niteroi - HCN, Niteroi, RJ (Brazil); Radiology Department, Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ (Brazil); Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, MD (United States); Radiology Department, Universidade Federal Fluminense - UFF, Niteroi, RJ (Brazil); Sarmet dos Santos, Alair Augusto Sarmet, E-mail: alairsarmet@globo.com [Hospital de Clinicas de Niteroi - HCN, Niteroi, RJ (Brazil); Radiology Department, Universidade Federal Fluminense - UFF, Niteroi, RJ (Brazil); Cury, Ricardo Caldeira, E-mail: RCury@baptisthealth.net [Baptist Cardiac and Vascular Institute, Miami, FL (United States); Rochitte, Carlos Eduardo, E-mail: rochitte@incor.usp.br [Department of Cardiovascular MRI and CT InCor - HCFMUSP, SP (Brazil); Marchiori, Edson, E-mail: edmarchiori@gmail.com [Radiology Department, Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ (Brazil); Radiology Department, Universidade Federal Fluminense - UFF, Niteroi, RJ (Brazil)

    2012-08-15

    Highlights: Black-Right-Pointing-Pointer In this study, we evaluated the accuracy of a Combined CMR protocol in the detection of significant CAD. Black-Right-Pointing-Pointer The invasive coronary angiography was the reference standard. Black-Right-Pointing-Pointer Results obtained in our study indicate that combination of perfusion and cine-MR during stress/rest, associated to delayed enhancement in the same protocol improves CMRI diagnostic accuracy and sensitivity for patients with significant coronary stenosis. Black-Right-Pointing-Pointer The Combined CMR protocol may therefore be helpful for risk stratification and defining treatment strategies. -- Abstract: Objective: To evaluate the diagnostic performance of stress perfusion cardiac MR (CMR) for detecting significant CAD ({>=}70% narrowing) in comparison with invasive coronary angiography (ICA) as a reference standard. Methods: Examinations of 54 patients who underwent both stress perfusion CMR and ICA for investigation of CAD between 2007 and 2009 were evaluated. The CMR protocol included dipyridamole stress and rest perfusion, stress and rest cine MRI for assessment of ventricular function and delayed gadolinium enhancement for assessment of myocardial viability and detection of infarction. CMR interpretation was performed by 2 observers blinded to the results of ICA and the clinical history. Results: From a total of 54 patients, 37 (68.5%) showed significant CAD in 71 coronary territories. A perfusion defect was detected in 35 patients and in 69 coronary territories. Individual stress perfusion CMR evaluation showed the highest accuracy (83%) of the CMR techniques. The combined analysis using all sequences increased the overall accuracy of CMR to 87%. Conclusion: Combination of perfusion and cine-MR during stress/rest, associated to delayed enhancement in the same protocol improves CMRI diagnostic accuracy and sensitivity for patients with significant coronary stenosis, and may therefore be helpful for

  19. Evaluation of Diagnostic Value in Using a Panel of Multiple Tumor-Associated Antigens for Immunodiagnosis of Cancer

    Directory of Open Access Journals (Sweden)

    Peng Wang

    2014-01-01

    Full Text Available To determine whether a panel of multiple tumor-associated antigens (TAAs would enhance antibody detection, the diagnostic value of autoantibodies to a panel of multiple TAAs in cancer has been evaluated. The TAAs used in this study was composed of eight TAAs including Imp1, p62, Koc, p53, C-myc, Cyclin B1, Survivin, and p16 full-length recombinant proteins. Enzyme-linked immunosorbent assay and immunoblotting were used to detect antibodies in 304 cancer sera and also 58 sera from normal individuals. The antibody frequency to any individual TAA in cancer was variable but rarely exceeded 20%. With the successive addition of TAAs to a final combination of total of eight antigens, there was a stepwise increase of positive antibody reactions reaching a sensitivity of 63.5% and a specificity of 86.2% in the combined cancer group. In different types of cancer, the ranges of positive and negative likelihood ratio were 4.07–4.76 and 0.39–0.51, respectively, and the ranges of positive and negative predictive values were 74.2–88.7% and 58.8–75.8%, respectively. Agreement rate and Kappa value were 67.1% and 0.51, respectively. These results further support our previous hypothesis that detection of anti-TAAs autoantibodies for diagnosis of certain type of cancer can be enhanced by using a miniarray of several TAAs.

  20. Diagnostic value of multiple café-au-lait macules for neurofibromatosis 1 in Chinese children.

    Science.gov (United States)

    Yao, Ruen; Wang, Lili; Yu, Yongguo; Wang, Jian; Shen, Yiping

    2016-05-01

    Neurofibromatosis 1 (NF1) is a common autosomal dominant condition caused by mutations in the NF1 gene. The appearance of multiple café-au-lait macules is an early sign of the condition, which often alert physicians to follow up and further examine the patient for the possibility of NF1. In order to determine the predictive value of multiple café-au-lait macules at early age for NF1 in Chinese patients, we recruited 19 children who shared the common sign of multiple café-au-lait macules from a general pediatric clinic in Shanghai. All the patients were clinically evaluated following the National Institutes of Health criteria for NF1 and molecular tested for sequence variants and copy number changes. Nine children met the clinical diagnostic criteria of NF1, and molecular tests confirmed all nine patients with pathogenic variants including two genomic deletions, two novel frame-shift variants, four novel nonsense and a splicing variants. In addition, four children who did not meet the diagnostic criteria were also found to carry pathogenic NF1 variants. Overall, 68.4% (13/19) of children with café-au-lait macules and various other clinical presentations were molecularly confirmed with NF1. This study demonstrated that the majority of Chinese children with multiple café-au-lait macules who came to seek for medical attention had NF1. Molecular testing is necessary to be used as an adjunct and sometimes as the main tool for confirming and diagnosing children of NF1 at early age. © 2015 Japanese Dermatological Association.

  1. Development of a multiple wavelength extinction diagnostic for measuring ejecta particle size distributions.

    Science.gov (United States)

    Steele, Paul; Compton, Steve; Jacoby, Barry; Filip, Catalin; Frank, Matthias; Phillips, Danial; Sinibaldi, Jose O.

    2017-06-01

    Mie's solution of Maxwell's equations for the interaction of light with spherical particles shows that particle diameter has a dramatic impact on the amount of light scattered or absorbed by a particle. The ratio of particle size to wavelength is particularly important. By measuring the transmission through a sheet of ejecta at multiple wavelengths and making certain assumptions, it is possible to estimate the ejecta particle size distribution. The Multiple Wavelength Extinction (MWE) diagnostic is being developed at Lawrence Livermore National Laboratory (LLNL) to do just that. Various potential system configurations were initially evaluated using a computer model developed in MATLAB. Inexpensive hardware (MWE Beta) was acquired for a basic proof-of-concept experiment using calibrated test particles. Encouraging results enabled procurement of better hardware. Characterization and testing of this MWE 1.0 system is ongoing. MWE 2.0 is now being designed. Ejecta experiments require a high explosive drive, an array of ejecta diagnostics and containment vessels, all of which are readily available at LLNL's High Explosives Application Facility. LLNL-ABS-723858. Prepared by LLNL under Contract DE-AC52-07NA27344.

  2. Smoldering multiple myeloma: pathophysiologic insights, novel diagnostics, clinical risk models, and treatment strategies.

    Science.gov (United States)

    Kazandjian, Dickran; Mailankody, Sham; Korde, Neha; Landgren, Ola

    2014-09-01

    Smoldering multiple myeloma (SMM) is a plasma cell disorder first described in 1980 when 6 patients were observed to meet the diagnostic criteria of multiple myeloma, defined as bone marrow plasmacytosis of 10% or greater or M protein level of 3 g/dL or greater, but did not have end-organ damage. Subsequent studies showed that the cumulative risk of SMM progression to symptomatic myeloma in 15 years was 73%. Since this time, advances have been made in understanding the biology of progression; namely, the contribution of branching evolution and microenvironment models to clonal heterogeneity. In parallel to this, clinical risk models using standard platforms of serum, bone marrow, and fluorescence in situ hybridization markers along with newer technologies of flow cytometry, gene expression profiling, and magnetic resonance imaging have been developed for prognostic stratification. Treatment has extended to the early myeloma category owing to more sensitive diagnostic approaches. The development of novel treatments will have to take into consideration our current knowledge of biological transformation. While it may be attractive to initiate early treatment in light of recent studies for high-risk SMM patients, clinical trial evidence of efficacy vs toxicity is still in its infancy. In our opinion, high-risk SMM patients should be strongly encouraged to enroll in treatment clinical trials, but treatment with unapproved agents or indications is not supported outside of trials.

  3. Development of a diagnostic test based on multiple continuous biomarkers with an imperfect reference test.

    Science.gov (United States)

    García Barrado, Leandro; Coart, Els; Burzykowski, Tomasz

    2016-02-20

    Ignoring the fact that the reference test used to establish the discriminative properties of a combination of diagnostic biomarkers is imperfect can lead to a biased estimate of the diagnostic accuracy of the combination. In this paper, we propose a Bayesian latent-class mixture model to select a combination of biomarkers that maximizes the area under the ROC curve (AUC), while taking into account the imperfect nature of the reference test. In particular, a method for specification of the prior for the mixture component parameters is developed that allows controlling the amount of prior information provided for the AUC. The properties of the model are evaluated by using a simulation study and an application to real data from Alzheimer's disease research. In the simulation study, 100 data sets are simulated for sample sizes ranging from 100 to 600 observations, with a varying correlation between biomarkers. The inclusion of an informative as well as a flat prior for the diagnostic accuracy of the reference test is investigated. In the real-data application, the proposed model was compared with the generally used logistic-regression model that ignores the imperfectness of the reference test. Conditional on the selected sample size and prior distributions, the simulation study results indicate satisfactory performance of the model-based estimates. In particular, the obtained average estimates for all parameters are close to the true values. For the real-data application, AUC estimates for the proposed model are substantially higher than those from the 'traditional' logistic-regression model. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Depression and multiple sclerosis: Review of a lethal combination

    National Research Council Canada - National Science Library

    Wallin, Mitchell T; Wilken, Jeffrey A; Turner, Aaron P; Williams, Rhonda M; Kane, Robert

    2006-01-01

    Depression is the most frequent psychiatric disorder in multiple sclerosis (MS) patients. The etiology of depression is multifactorial and likely associated with psychosocial stress, focal demyelinating lesions, and immune dysfunction...

  5. Individual and Combined Responses of Stream Ecosystems to Multiple Stressors

    National Research Council Canada - National Science Library

    Colin R. Townsend; S. Sebastian Uhlmann; Christoph D. Matthaei

    2008-01-01

    1. Managers must understand the effects of stressors on ecosystems in order to identify thresholds of harm but, to be meaningful, thresholds will usually need to be defined for situations where multiple...

  6. Quality of Diagnosis and Treatment Plans After Using the 'Diagnostic Guideline for Anxiety and Challenging Behaviours' in People with Intellectual Disabilities: A Comparative Multiple Case Study Design.

    Science.gov (United States)

    Pruijssers, Addy; van Meijel, Berno; Maaskant, Marian; Keeman, Noortje; van Achterberg, Theo

    2016-07-01

    People with intellectual disabilities often have a multitude of concurrent problems due to the combination of cognitive impairments, psychiatric disorders (particularly anxiety) and related challenging behaviours. Diagnoses in people with intellectual disabilities are complicated. This study evaluates the quality of the diagnoses and treatment plans after using a guideline that was developed to support professionals in their diagnostic tasks. A comparative multiple case study with an experimental and control condition, applying deductive analyses of diagnoses and treatment plans. The analyses revealed that the number of diagnostic statements and planned treatment actions in the experimental group was significantly larger and more differentiated than in the control condition. In the control group, consequential harm and protective factors were hardly mentioned in diagnoses and treatment plans. Working with the 'Diagnostic Guideline for Anxiety and CB' leads to improved diagnoses and treatment plans compared with care as usual. © 2015 John Wiley & Sons Ltd.

  7. Diagnostic value of combined static-excretory MR Urography in children with hydronephrosis

    OpenAIRE

    Emad-Eldin, Sally; Abdelaziz, Omar; El-Diasty, Tarek A.

    2014-01-01

    The aim of this study was to determine the feasibility, accuracy and diagnostic potential of combined static-excretory MR Urography in children with sonographically detected hydronephrosis. We prospectively evaluated 28 children (11 girls and 17 boys), mean age 8.3 years (range 2 months–16 years). Static-excretory MR Urography was performed in all cases. The results of MR Urography were compared with the results of other imaging modalities, cystoscopy and surgery. In 28 children, 61 renal uni...

  8. The cultural formulation: A model to combine nosology and patients' life context in psychiatric diagnostic practice.

    Science.gov (United States)

    Bäärnhielm, Sofie; Scarpinati Rosso, Marco

    2009-09-01

    This article discusses the experience of adapting and applying the Outline for a Cultural Formulation in DSM-IV to the Swedish context. Findings from a research project on the Cultural Formulation highlight the value of combining psychiatric nosological categorization with an understanding of patients' cultural life context in order to increase the validity of categorization and to formulate individualized treatment plans. In clinical care practitioners need models and tools that help them take into account patients' cultural backgrounds, needs, and resources in psychiatric diagnostic practice. We present a summary of a Swedish manual for conducting a Cultural Formulation interview. The need for further development of the Cultural Formulation is also discussed.

  9. Combining item response theory and diagnostic classification models: a psychometric model for scaling ability and diagnosing misconceptions.

    Science.gov (United States)

    Bradshaw, Laine; Templin, Jonathan

    2014-07-01

    Traditional testing procedures typically utilize unidimensional item response theory (IRT) models to provide a single, continuous estimate of a student's overall ability. Advances in psychometrics have focused on measuring multiple dimensions of ability to provide more detailed feedback for students, teachers, and other stakeholders. Diagnostic classification models (DCMs) provide multidimensional feedback by using categorical latent variables that represent distinct skills underlying a test that students may or may not have mastered. The Scaling Individuals and Classifying Misconceptions (SICM) model is presented as a combination of a unidimensional IRT model and a DCM where the categorical latent variables represent misconceptions instead of skills. In addition to an estimate of ability along a latent continuum, the SICM model provides multidimensional, diagnostic feedback in the form of statistical estimates of probabilities that students have certain misconceptions. Through an empirical data analysis, we show how this additional feedback can be used by stakeholders to tailor instruction for students' needs. We also provide results from a simulation study that demonstrate that the SICM MCMC estimation algorithm yields reasonably accurate estimates under large-scale testing conditions.

  10. What is the added value of combined core biopsy and fine needle aspiration in the diagnostic process of renal tumours?

    NARCIS (Netherlands)

    Barwari, K.; Kummerlin, I. P.; ten Kate, F. J.; Algaba, F.; Trias, I.; Wijkstra, H.; de la Rosette, J. J.; Laguna, P.

    2013-01-01

    Non-diagnostic results still hinder the routine use of core biopsy (CB) and fine needle aspiration (FNA) in the diagnostic process of renal tumours. Furthermore, substantial interobserver variability has been reported. We assessed the added value of combining the results of CB and FNA by five

  11. Validation and analysis of the coupled multiple response Colorado upper-division electrostatics diagnostic

    Directory of Open Access Journals (Sweden)

    Bethany R. Wilcox

    2015-11-01

    Full Text Available Standardized conceptual assessment represents a widely used tool for educational researchers interested in student learning within the standard undergraduate physics curriculum. For example, these assessments are often used to measure student learning across educational contexts and instructional strategies. However, to support the large-scale implementation often required for cross-institutional testing, it is necessary for these instruments to have question formats that facilitate easy grading. Previously, we created a multiple-response version of an existing, validated, upper-division electrostatics diagnostic with the goal of increasing the instrument’s potential for large-scale implementation. Here, we report on the validity and reliability of this new version as an independent instrument. These findings establish the validity of the multiple-response version as measured by multiple test statistics including item difficulty, item discrimination, and internal consistency. Moreover, we demonstrate that the majority of student responses to the new version are internally consistent even when they are incorrect and provide an example of how the new format can be used to gain insight into student difficulties with specific content in electrostatics.

  12. Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests

    DEFF Research Database (Denmark)

    Ndyomugyenyi, Richard; Magnussen, Pascal; Lal, Sham

    2016-01-01

    OBJECTIVE: To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children artemisinin-based combination therapy (ACT), vs. presumptive treatment. METHODS: Cluster...

  13. Multiple sclerosis: imaging, diagnostic criteria and differential diagnosis; Bildgebung, Diagnosekriterien und Differenzialdiagnose der Multiplen Sklerose

    Energy Technology Data Exchange (ETDEWEB)

    Harting, I.; Sartor, K. [Abt. Neuroradiologie, Neurologische Klinik, Universitaetsklinikum Heidelberg (Germany); Sellner, J.; Meyding-Lamade, U. [Abt. Neurologie, Neurologische Klinik, Universitaetsklinikum Heidelberg (Germany)

    2003-05-01

    Multiple sclerosis (MS) is the most common demyelinating inflammatory disease of the central nervous system (CNS), presenting with multifocal, disseminated inflammatory lesions referred to as plaques. Magnetic resonance imaging (MRI) typically depicts multiple, round to oval, circumscript lesions predominantly involving periventricular and subcortical white matter, brainstem and cerebellum. More recent investigations have demonstrated that the macroscopically visible plaques only present the tip of the iceberg: Already early in its course, MS causes neuroaxonal damage and diffusely involves the entire brain parenchyma including normal appearing white matter. These changes are reflected by strongly T{sub 1}w hypointense lesions and atrophy of early onset, by reduction of the neuronal Marker N-acetylaspartate (NAA) on spectroscopy, by a decrease of the magnetization transfer ratio (MTR), by an increased in diffusibility and decreased anisotropy on diffusion-weighted imaging (DWI). MRI imaging is an important tool in the diagnosis of MS by revealing the characteristic spatial and temporal dissemination of the cerebral and spinal manifestations of this disease. Diagnostic criteria increase the diagnostic specificity and allow better differentiation from other diseases with multifocal white matter abnormalities. (orig.) [German] Die multiple sklerose (MS) ist die haeufigste entzuendliche, demyelinisierende Erkrankung des zentralen Nervensystems (ZNS) Sie ist durch multifokale, disseminierte Entzuendungsherde, sogenannte Plaques, in den myelinhaltigen Strukturen des ZNS charakterisiert. In der Magnetresonanztomographie (MRT) sind multiple umschriebene, rundlich-ovale Laesionen der weissen Substanz charakteristisch, die bevorzugt im periventrikulaeren Marklager, an der Mark-Rindengrenze, im Hirnstamm und im Kleinhirn lokalisiert sind. Neuere Untersuchungen zeigen, dass die sichtbaren Entmarkungsherde nur die Spitze des Eisbergs sind: Bereits fruehzeitig verursacht die MS

  14. Noise characterization of weighting schemes for combination of multiple exposures

    DEFF Research Database (Denmark)

    Kirk, Kristian; Andersen, Hans Jørgen

    2006-01-01

    A method for capturing high intensity dynamic range scenes with a low dynamic range camera consists in taking a series of images with different exposure settings and combining these into a single high dynamic range image. The combined image values are found by weighted averaging of values from...... the differently exposed images on a per-pixel basis. This paper reviews existing weighting schemes and considers their noise properties. Furthermore, a minimum-variance solution is introduced which exploits a camera noise model. Special emphasis is on the case when the camera is linear. A method is given...

  15. Multiple-instance learning as a classifier combining problem

    DEFF Research Database (Denmark)

    Li, Yan; Tax, David M. J.; Duin, Robert P. W.

    2013-01-01

    posteriors. Given the instance labels, the label of a bag can be obtained as a classifier combining problem. An optimal decision rule is derived that determines the threshold on the fraction of instances in a bag that is assigned to the concept class. We provide estimators for the two parameters in the model...... with the assumption that instances are drawn from a mixture distribution of the concept and the non-concept, which leads to a convenient way to solve MIL as a classifier combining problem. It is shown that instances can be classified with any standard supervised classifier by re-weighting the classification...

  16. Facile integration of multiple magnetite nanoparticles for theranostics combining efficient MRI and thermal therapy

    Science.gov (United States)

    Huang, Guoming; Zhu, Xianglong; Li, Hui; Wang, Lirong; Chi, Xiaoqin; Chen, Jiahe; Wang, Xiaomin; Chen, Zhong; Gao, Jinhao

    2015-01-01

    Multifunctional nanostructures with both diagnostic and therapeutic capabilities have attracted considerable attention in biomedical research because they can offer great advantages in disease management and prognosis. In this work, a facile way to transfer the hydrophobic iron oxide (IO) nanoparticles into aqueous media by employing carboxylic graphene oxide (GO-COOH) as the transferring agent has been reported. In this one-step process, IO nanoparticles adhere to GO-COOH and form water-dispersible clusters via hydrophobic interactions between the hydrophobic ligands of IO nanoparticles and the basal plane of GO-COOH. The multiple IO nanoparticles on GO-COOH sheets (IO/GO-COOH) present a significant increase in T2 contrast enhancement. Moreover, the IO/GO-COOH nanoclusters also display a high photothermal conversion efficiency and can effectively inhibit tumor growth through the photothermal effects. It is envisioned that such IO/GO-COOH nanocomposites combining efficient MRI and photothermal therapy hold great promise in theranostic applications.Multifunctional nanostructures with both diagnostic and therapeutic capabilities have attracted considerable attention in biomedical research because they can offer great advantages in disease management and prognosis. In this work, a facile way to transfer the hydrophobic iron oxide (IO) nanoparticles into aqueous media by employing carboxylic graphene oxide (GO-COOH) as the transferring agent has been reported. In this one-step process, IO nanoparticles adhere to GO-COOH and form water-dispersible clusters via hydrophobic interactions between the hydrophobic ligands of IO nanoparticles and the basal plane of GO-COOH. The multiple IO nanoparticles on GO-COOH sheets (IO/GO-COOH) present a significant increase in T2 contrast enhancement. Moreover, the IO/GO-COOH nanoclusters also display a high photothermal conversion efficiency and can effectively inhibit tumor growth through the photothermal effects. It is envisioned

  17. Convex Combination of Multiple Statistical Models with Application to VAD

    DEFF Research Database (Denmark)

    Petsatodis, Theodoros; Boukis, Christos; Talantzis, Fotios

    2011-01-01

    statistical distributions - a Gaussian, a Laplacian, and a two-sided Gamma - to effectively model captured speech. This scheme shows increased ability to adapt to dynamic acoustic environments. The contribution of each distribution to this convex combination is automatically adjusted based on the statistical...

  18. Learning Combinations of Multiple Feature Representations for Music Emotion Prediction

    DEFF Research Database (Denmark)

    Madsen, Jens; Jensen, Bjørn Sand; Larsen, Jan

    2015-01-01

    Music consists of several structures and patterns evolving through time which greatly influences the human decoding of higher-level cognitive aspects of music like the emotions expressed in music. For tasks, such as genre, tag and emotion recognition, these structures have often been identified...... and used as individual and non-temporal features and representations. In this work, we address the hypothesis whether using multiple temporal and non-temporal representations of different features is beneficial for modeling music structure with the aim to predict the emotions expressed in music. We test...

  19. Combined functional and anatomical diagnostic endpoints for assessing arteriovenous fistula dysfunction.

    Science.gov (United States)

    Rajabi-Jaghargh, Ehsan; Banerjee, Rupak K

    2015-02-06

    diagnostic endpoints that can combine the effects of pressure and flow. These new hemodynamic diagnostic endpoints have shown to be better predictors of functional severity of lesions as compared to either flow or pressure based counterparts. In this review article, we discussed the advantages and limitations of current functional and anatomical diagnostic endpoints in AVFs.

  20. Using Robust Standard Errors to Combine Multiple Regression Estimates with Meta-Analysis

    Science.gov (United States)

    Williams, Ryan T.

    2012-01-01

    Combining multiple regression estimates with meta-analysis has continued to be a difficult task. A variety of methods have been proposed and used to combine multiple regression slope estimates with meta-analysis, however, most of these methods have serious methodological and practical limitations. The purpose of this study was to explore the use…

  1. Survey of diagnostic and treatment practices for multiple sclerosis in Europe.

    Science.gov (United States)

    Fernández, O; Delvecchio, M; Edan, G; Fredrikson, S; Gionvannoni, G; Hartung, H-P; Havrdova, E; Kappos, L; Pozzilli, C; Soerensen, P S; Tackenberg, B; Vermersch, P; Comi, G

    2017-03-01

    Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice. A steering committee of MS neurologists used a modified Delphi process to develop case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case-based questions were developed for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and RRMS with breakthrough disease. Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe. © 2017 EAN.

  2. Combined adaptive multiple subtraction based on optimized event tracing and extended wiener filtering

    Science.gov (United States)

    Tan, Jun; Song, Peng; Li, Jinshan; Wang, Lei; Zhong, Mengxuan; Zhang, Xiaobo

    2017-06-01

    The surface-related multiple elimination (SRME) method is based on feedback formulation and has become one of the most preferred multiple suppression methods used. However, some differences are apparent between the predicted multiples and those in the source seismic records, which may result in conventional adaptive multiple subtraction methods being barely able to effectively suppress multiples in actual production. This paper introduces a combined adaptive multiple attenuation method based on the optimized event tracing technique and extended Wiener filtering. The method firstly uses multiple records predicted by SRME to generate a multiple velocity spectrum, then separates the original record to an approximate primary record and an approximate multiple record by applying the optimized event tracing method and short-time window FK filtering method. After applying the extended Wiener filtering method, residual multiples in the approximate primary record can then be eliminated and the damaged primary can be restored from the approximate multiple record. This method combines the advantages of multiple elimination based on the optimized event tracing method and the extended Wiener filtering technique. It is an ideal method for suppressing typical hyperbolic and other types of multiples, with the advantage of minimizing damage of the primary. Synthetic and field data tests show that this method produces better multiple elimination results than the traditional multi-channel Wiener filter method and is more suitable for multiple elimination in complicated geological areas.

  3. Incremental diagnostic value of combined quantitative and qualitative parameters of magnetocardiography to detect coronary artery disease.

    Science.gov (United States)

    Shin, Eun-Seok; Lam, Yat-Yin; Her, Ae-Young; Brachmann, Johannes; Jung, Friedrich; Park, Jai-Wun

    2017-02-01

    Magnetocardiography (MCG) has been proposed as a non-invasive and functional technique with high accuracy for diagnosis of myocardial ischemia. This study sought to investigate the incremental diagnostic value of combined quantitative and qualitative parameters of MCG to detect coronary artery disease (CAD). Ninety six patients with suspected CAD who underwent coronary angiography were enrolled in the analysis to test the diagnostic accuracy of 2 MCG parameters (a quantitative parameter of the percent change of ST-segment fluctuation score and a qualitative parameter of non-dipole phenomenon). The best cut-off value for the percent change of ST-segment fluctuation score was -51.0%. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 78.1, 73.9, 82.0, 79.1, and 77.4, in the percent change of ST-segment fluctuation score and 86.5, 84.8, 88.0, 86.7, and 86.3 in non-dipole phenomenon. The area under the curve of receiver-operating characteristics was 0.79 for the percent change of ST-segment fluctuation score and 0.86 for non-dipole phenomenon (pquantitative parameter of percent change of ST-segment fluctuation score in the detection of significant CAD. Furthermore, this study found that the incorporation of non-dipole phenomenon into the percent change of ST-segment fluctuation score significantly improved the diagnostic performance of CAD detection. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. GENERAL: A combined statistical model for multiple motifs search

    Science.gov (United States)

    Gao, Li-Feng; Liu, Xin; Guan, Shan

    2008-12-01

    Transcription factor binding sites (TFBS) play key roles in genebior 6.8 wavelet expression and regulation. They are short sequence segments with definite structure and can be recognized by the corresponding transcription factors correctly. From the viewpoint of statistics, the candidates of TFBS should be quite different from the segments that are randomly combined together by nucleotide. This paper proposes a combined statistical model for finding over-represented short sequence segments in different kinds of data set. While the over-represented short sequence segment is described by position weight matrix, the nucleotide distribution at most sites of the segment should be far from the background nucleotide distribution. The central idea of this approach is to search for such kind of signals. This algorithm is tested on 3 data sets, including binding sites data set of cyclic AMP receptor protein in E.coli, PlantProm DB which is a non-redundant collection of proximal promoter sequences from different species, collection of the intergenic sequences of the whole genome of E.Coli. Even though the complexity of these three data sets is quite different, the results show that this model is rather general and sensible.

  5. Diagnostic value of combined static-excretory MR Urography in children with hydroneph

    Directory of Open Access Journals (Sweden)

    Sally Emad-Eldin

    2015-03-01

    Full Text Available The aim of this study was to determine the feasibility, accuracy and diagnostic potential of combined static-excretory MR Urography in children with sonographically detected hydronephrosis. We prospectively evaluated 28 children (11 girls and 17 boys, mean age 8.3 years (range 2 months–16 years. Static-excretory MR Urography was performed in all cases. The results of MR Urography were compared with the results of other imaging modalities, cystoscopy and surgery. In 28 children, 61 renal units were evaluated by MR Urography (the renal unit is the kidney and its draining ureter. The final diagnoses included: normal renal units (n = 23; uretropelvic junction obstruction (n = 14; megaureter (n = 8; midureteric stricture (n = 1, complicated duplicated systems (n = 5, post ESWL non-obstructive dilation (n = 2, extrarenal pelvis (n = 4, dysplastic kidney (n = 4. Complex pathology and more than one disease entity in were found in 7 children. The MRI diagnosis correlated with the final diagnosis in 57 units, with diagnostic accuracy 93.4%. In conclusions static and excretory MRU give both morphological and functional information in a single examination without exposure to ionizing radiation and iodinated contrast agent. It is a valuable imaging technique for children with upper urinary tract dilatation; especially in cases of complex congenital pathologies and severely hydronephrotic kidney.

  6. Diagnostic value of combined static-excretory MR Urography in children with hydronephrosis.

    Science.gov (United States)

    Emad-Eldin, Sally; Abdelaziz, Omar; El-Diasty, Tarek A

    2015-03-01

    The aim of this study was to determine the feasibility, accuracy and diagnostic potential of combined static-excretory MR Urography in children with sonographically detected hydronephrosis. We prospectively evaluated 28 children (11 girls and 17 boys), mean age 8.3 years (range 2 months-16 years). Static-excretory MR Urography was performed in all cases. The results of MR Urography were compared with the results of other imaging modalities, cystoscopy and surgery. In 28 children, 61 renal units were evaluated by MR Urography (the renal unit is the kidney and its draining ureter). The final diagnoses included: normal renal units (n = 23); uretropelvic junction obstruction (n = 14); megaureter (n = 8); midureteric stricture (n = 1), complicated duplicated systems (n = 5), post ESWL non-obstructive dilation (n = 2), extrarenal pelvis (n = 4), dysplastic kidney (n = 4). Complex pathology and more than one disease entity in were found in 7 children. The MRI diagnosis correlated with the final diagnosis in 57 units, with diagnostic accuracy 93.4%. In conclusions static and excretory MRU give both morphological and functional information in a single examination without exposure to ionizing radiation and iodinated contrast agent. It is a valuable imaging technique for children with upper urinary tract dilatation; especially in cases of complex congenital pathologies and severely hydronephrotic kidney.

  7. Diagnostic Value of Dual-Source Computerized Tomography Combined with Perfusion Imaging for Peripheral Pulmonary Embolism

    Science.gov (United States)

    Mao, Xijin; Wang, Shanshan; Jiang, Xingyue; Zhang, Lin; Xu, Wenjian

    2016-01-01

    Background Pulmonary embolism has become the third most common cardiovascular disease, which can seriously harm human health. Objectives To investigate the diagnostic value of dual-source computerized tomography (CT) and perfusion imaging for peripheral pulmonary embolism. Patients and Methods Thirty-two patients with suspected pulmonary embolism underwent dual-source CT exams. To compare the ability of pulmonary embolism detection software (PED) with CT pulmonary angiography (CTPA) in determining the presence, numbers, and locations of pulmonary emboli, the subsequent images were reviewed by two radiologists using both imaging modalities. Also, the diagnostic consistency between PED and CTPA images and dual-energy pulmonary perfusion imaging (DEPI) for segmental pulmonary embolism was compared. Results CTPA images revealed 50 (7.81%) segmental and 56 (4.38%) sub-segmental pulmonary embolisms, while the PED images showed 68 (10.63%) segmental and 94 (7.34%) sub-segmental pulmonary embolisms. Thus, the detection rate on PED images for peripheral pulmonary embolism was significantly higher than that of the CTPA images (P pulmonary embolism between PED and CTPA and DEPI (kappa = 0.85). The sensitivity and specificity of DEPI images for the diagnosis of pulmonary embolism were 91.7% and 97.5%, respectively. Conclusion PED software of dual-source CT combined with perfusion imaging can significantly improve the detection rate of peripheral pulmonary embolism. PMID:27703656

  8. Combination of interferon and dexamethasone in refractory multiple myeloma.

    Science.gov (United States)

    San Miguel, J F; Moro, M; Bladé, J; Guerras, L; Hernandez, J; Jimenez-Galindo, R; Ortega, F; Gonzalez, M

    1990-01-01

    The present pilot study was designed to analyse the efficacy and toxicity of the association of interferon (IFN) and dexamethasone (Dx) in 32 resistant and relapsed myeloma patients. Among the evaluable cases, 15 (68 per cent) responded to treatment (32 per cent achieved an objective response--OR--and 36 per cent a partial response--PR--), the 'remission' status lasting for more than one year in six of them. Moreover, four out of the seven OR patients showed a reduction in B.M. plasma cells to less than 5 per cent. Five out of 11 patients that were previously refractory to VBAD, that includes high dose dexamethasone (Dx), responded to IFN-Dx. The protocol was generally well tolerated with only four patients discontinuing therapy due to adverse effects. The present results show that the combination IFN + Dx is a promising therapeutic approach for patients with refractory myeloma.

  9. Predicting Lung Volume Reduction after Endobronchial Valve Therapy Is Maximized Using a Combination of Diagnostic Tools.

    Science.gov (United States)

    Koster, T David; van Rikxoort, Eva M; Huebner, Ralf-Harto; Doellinger, Felix; Klooster, Karin; Charbonnier, Jean-Paul; Radhakrishnan, Sri; Herth, Felix J F; Slebos, Dirk-Jan

    2016-01-01

    Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) has been proven to be effective in patients with severe emphysema. However, the selection of patients without collateral ventilation prior to treatment is critical for procedural success. Collateral ventilation can be assessed directly with the Chartis system or indirectly using computed tomography (CT) fissure analysis. We retrospectively evaluated the diagnostic value of a combination of the quantitative CT interlobar fissure completeness score (FCS) and Chartis in predicting responders to EBV therapy. CT data from four prospective studies were pooled and analyzed using semiautomated software to quantify the completeness of interlobar fissures. These FCSs were compared to a reference standard of achieving ≥350 ml of target lobe volume reduction after EBV treatment. Using a receiver operating characteristic curve, optimal thresholds predictive of complete fissures (responders) and incomplete fissures (non-responders) were determined. A subgroup of patients with partially complete fissures was identified, where software had lower accuracy. The complementary value of Chartis was investigated in this group. A fissure was defined as complete (FCS >95%), incomplete (FCS <80%), or partially complete (80% < FCS < 95%). The positive predictive value (PPV) of complete fissures is 88.1%, and the negative predictive value (NPV) is 92.9%, with an overall accuracy of 89.2%. Chartis was utilized in patients with partially complete fissures, with a PPV of 82.3%, an NPV of 84.6%, and an accuracy of 83.3%. Combining diagnostic tools could reduce the burden on patients and the healthcare system while providing clinicians with a better means for patient selection for EBV therapy. © 2016 S. Karger AG, Basel.

  10. Combining a thermal-imaging diagnostic with an existing imaging VISAR diagnostic at the National Ignition Facility (NIF)

    Energy Technology Data Exchange (ETDEWEB)

    Robert M. Malone; John R. Celesteb; Peter M. Celliers; Brent C. Froggeta; Robert L. Guyton; Morris I. Kaufman; Tony L. Lee; Brian J. MacGowan; Edmund W. Ng; Imants P. Reinbachs; Ronald B. Robinson; Lynn G. Seppala; Tom W. Tunnell; Phillip W. Watts

    2005-01-01

    Optical diagnostics are currently being designed to analyze high-energy density physics experiments at the National Ignition Facility (NIF). Two independent line-imaging Velocity Interferometer System for Any Reflector (VISAR) interferometers have been fielded to measure shock velocities, breakout times, and emission of targets having sizes of 1–5 mm. An 8-inch-diameter, fused silica triplet lens collects light at f/3 inside the 30-foot-diameter NIF vacuum chamber. VISAR recordings use a 659.5-nm probe laser. By adding a specially coated beam splitter to the interferometer table, light at wavelengths from 540 to 645 nm is spilt into a thermal-imaging diagnostic. Because fused silica lenses are used in the first triplet relay, the intermediate image planes for different wavelengths separate by considerable distances. A corrector lens on the interferometer table reunites these separated wavelength planes to provide a good image. Thermal imaging collects light at f/5 from a 2-mm object placed at Target Chamber Center (TCC). Streak cameras perform VISAR and thermal-imaging recording. All optical lenses are on kinematic mounts so that pointing accuracy of the optical axis may be checked. Counter-propagating laser beams (orange and red) are used to align both diagnostics. The red alignment laser is selected to be at the 50 percent reflection point of the beam splitter. This alignment laser is introduced at the recording streak cameras for both diagnostics and passes through this special beam splitter on its way into the NIF vacuum chamber.

  11. Combining a thermal-imaging diagnostic with an existing imaging VISAR diagnostic at the National Ignition Facility (NIF)

    Energy Technology Data Exchange (ETDEWEB)

    Malone, R; Celeste, J; Celliers, P; Frogget, B; Guyton, R L; Kaufman, M; Lee, T; MacGowan, B; Ng, E W; Reinbachs, I P; Robinson, R B; Seppala, L; Tunnell, T W; Watts, P

    2005-07-07

    Optical diagnostics are currently being designed to analyze high-energy density physics experiments at the National Ignition Facility (NIF). Two independent line-imaging Velocity Interferometer System for Any Reflector (VISAR) interferometers have been fielded to measure shock velocities, breakout times, and emission of targets having sizes of 1-5 mm. An 8-inch-diameter, fused silica triplet lens collects light at f/3 inside the 30-foot-diameter NIF vacuum chamber. VISAR recordings use a 659.5-nm probe laser. By adding a specially coated beam splitter to the interferometer table, light at wavelengths from 540 to 645 nm is spilt into a thermal-imaging diagnostic. Because fused silica lenses are used in the first triplet relay, the intermediate image planes for different wavelengths separate by considerable distances. A corrector lens on the interferometer table reunites these separated wavelength planes to provide a good image. Thermal imaging collects light at f/5 from a 2-mm object placed at Target Chamber Center (TCC). Streak cameras perform VISAR and thermal-imaging recording. All optical lenses are on kinematic mounts so that pointing accuracy of the optical axis may be checked. Counter-propagating laser beams (orange and red) are used to align both diagnostics. The red alignment laser is selected to be at the 50 percent reflection point of the beam splitter. This alignment laser is introduced at the recording streak cameras for both diagnostics and passes through this special beam splitter on its way into the NIF vacuum chamber.

  12. Diagnostic value of PET/CT for giant cell arteritis combined with pulmonary embolism presenting

    Science.gov (United States)

    Shu, Xiaoming; Xu, Xiaoxiang; Peng, Qinglin; Lu, Xin; Ma, Li; Mi, Na; Wang, Guochun

    2017-01-01

    Abstract Rationale: Giant cell arteritis (GCA) combined with concomitant pulmonary embolism (PE) is extremely difficult to diagnose because of its low incidence and atypical clinical presentations. Patient concerns: A 62-year-old male developed fever of unknown origin. Diagnoses: Positron emission tomography/computed tomography (PET/CT) revealed increased glucose metabolism in the vascular walls of the ascending and descending aorta and pulmonary artery, leading to a diagnosis of GCA combined with PE. Interventions: The patient did not respond to regular antiviral and antibacterial treatment but was remised after steroid treatment. Outcomes: No specific autoantibodies were positive for this patient, and the patient did not respond to regular antiviral and antibacterial treatment. After diagnosed by PET/CT, the patient responded well to steroid treatment. Literature review found 16 cases of GCA diagnosed by PET/CT. Their median age was 68.5 (range, 21–87) years and 13 cases were female. PET/CT showed significantly increased metabolism in the ascending and descending aorta, abdominal aorta, and carotid artery. In 4 cases (including our own case), the mean maximum standardized uptake value was 4.2 ± 1.7 (range, 2.5–7.2). Six cases of GCA also had PE and 5 (6/7, 85.7%) cases were females, and the current case is the first male case of GCA combined with PE. Steroid therapy was initiated in all 5 cases. Complete remission was achieved in 4 cases and 2 patients died and the outcome of 1 patient was unknown. Lessons: Our case and the review highlight the value of PET/CT in diagnosing GCA combined with PE, suggesting that PET/CT is the preferred diagnostic tool for atypical patients presenting with fever or muscle pain. PMID:28767581

  13. [Primary progressive forms of multiple sclerosis: application of the new diagnostic criteria in French].

    Science.gov (United States)

    De Seze, J; Mackowiak, A; Stojkovic, T; Ferriby, D; Hautecoeur, P; Vermersch, P

    2002-03-01

    Approximately 15 p.100 of all cases of multiple sclerosis (MS) are primary progressive multiple sclerosis (PPMS). Diagnosis is however frequently delayed due to the lack of relapse. The commonly used Poser criteria established in 1983 are not directly applicable to this subgroup of MS patients. In 2000, Thompson et al proposed new diagnostic criteria for PPMS. The aim of our study was to apply retrospectively these new criteria to a cohort of patients from northern France (G-SEP cohort). The cohort included 184 patients (94 women and 90 men, sex ratio=1.04). Mean age at disease onset was 40.3 years (18-67 years) and mean follow-up was 9.9 (1-39 years). Only one patient was older than 65 years but 13 patients (7.1 p.100) were younger than 25 years. Patients were classed as having definite, probable or possible PPMS on the basis of clinical, MRI, cerebrospinal fluid and visual evoked potential (VEP) data. Most of the patients (61.4 p.100) had one symptom at onset; spastic paraparesis was frequent (79 p.100). Mean delay to diagnosis was 4.4 years. Ten patients (5.4 p.100) were surgically treated for cervic arthrosic myelopathy. Mean EDSS score at the end of follow-up was 5.8 (3-10). MRI was positive in 87.3 p.100 of the patients. Oligoclonal bands were found in 78.2 p.100. VEPs ware abnormal in 79.9 p.100 of the patients. Applying the Thompson criteria, 57.7 p.100 of the patients had definite PPMS, 38.7 p.100 probable PPMS. Our results are very similar to previous studies and confirm the usefulness of the new proposed criteria, which however should be prospectively tested to determine sensitivity and specificity in a new cohort of patients.

  14. Diagnoses and clinical outcomes associated with surgically amputated feline digits submitted to multiple veterinary diagnostic laboratories.

    Science.gov (United States)

    Wobeser, B K; Kidney, B A; Powers, B E; Withrow, S J; Mayer, M N; Spinato, M T; Allen, A L

    2007-05-01

    Amputation is commonly performed in an attempt to both treat and diagnose conditions affecting the digits of cats. The records of multiple veterinary diagnostic laboratories were searched to identify submissions of amputated digits from cats. Eighty-five separate submissions were reviewed for diagnosis, age, sex, limb of origin, and digits affected; and the original submitting clinics were surveyed to determine clinical outcome. The Kaplan-Meier product-limit method was used to determine the disease-free interval and survival time. Neoplastic disease was identified in 63 of 85 submissions, with exclusively inflammatory lesions composing the other 22 cases. In 60 (95.2%) of the neoplastic cases, a malignant tumor was identified. Squamous cell carcinoma was the most commonly identified malignant tumor (n = 15; 23.8%) and was associated with a median survival time of 73 days. Other diagnoses included fibrosarcoma (n = 14; 22.2%); adenocarcinoma, likely metastases of a primary pulmonary neoplasm (n = 13; 20.6%); osteosarcoma (n = 5; 7.9%); mast cell tumor (n = 4; 6.3%); hemangiosarcoma (n = 5; 7.9%); malignant fibrous histiocytoma (n = 2; 3.2%); giant cell tumor of bone (n = 2; 3.2%); and hemangioma (n = 2; 3.2%). Giant cell tumor of bone has not been previously described in the digits of cats. Various neoplasms can occur in the digits of cats, and submission of the amputated digit for histopathologic diagnosis is essential to determine the histogenesis and predict the clinical outcome.

  15. Detecting Renibacterium salmoninarum in wild brown trout by use of multiple organ samples and diagnostic methods

    Science.gov (United States)

    Guomundsdottir, S.; Applegate, Lynn M.; Arnason, I.O.; Kristmundsson, A.; Purcell, Maureen K.; Elliott, Diane G.

    2017-01-01

    Renibacterium salmoninarum, the causative agent of salmonid bacterial kidney disease (BKD), is endemic in many wild trout species in northerly regions. The aim of the present study was to determine the optimal R. salmoninarum sampling/testing strategy for wild brown trout (Salmo trutta L.) populations in Iceland. Fish were netted in a lake and multiple organs—kidney, spleen, gills, oesophagus and mid-gut—were sampled and subjected to five detection tests i.e. culture, polyclonal enzyme-linked immunosorbent assay (pELISA) and 3 three different PCR tests. The results showed that each fish had encountered R. salmoninarum but there were marked differences between results obtained depending on organ and test. The bacterium was not cultured from any kidney sample while all kidney samples were positive by pELISA. At least one organ from 92.9% of the fish tested positive by PCR. The results demonstrated that the choice of tissue and diagnostic method can dramatically influence the outcome of R. salmoninarum surveys.

  16. Development of Pathological Diagnostics of Human Kidney Cancer by Multiple Staining Using New Fluorescent Fluolid Dyes

    Directory of Open Access Journals (Sweden)

    Dilibaier Wuxiuer

    2014-01-01

    Full Text Available New fluorescent Fluolid dyes have advantages over others such as stability against heat, dryness, and excess light. Here, we performed simultaneous immunostaining of renal tumors, clear cell renal cell carcinoma (RCC, papillary RCC, chromophobe RCC, acquired cystic disease-associated RCC (ACD-RCC, and renal angiomyolipoma (AML, with primary antibodies against Kank1, cytokeratin 7 (CK7, and CD10, which were detected with secondary antibodies labeled with Fluolid-Orange, Fluolid-Green, and Alexa Fluor 647, respectively. Kank1 was stained in normal renal tubules, papillary RCC, and ACD-RCC, and weakly or negatively in all other tumors. CK7 was positive in normal renal tubules, papillary RCC, and ACD-RCC. In contrast, CD10 was expressed in renal tubules and clear cell RCC, papillary RCC, AML, and AC-RCC, and weakly in chromophobe RCC. These results may contribute to differentiating renal tumors and subtypes of RCCs. We also examined the stability of fluorescence and found that fluorescent images of Fluolid dyes were identical between a tissue section and the same section after it was stored for almost three years at room temperature. This indicates that tissue sections can be stored at room temperature for a relatively long time after they are stained with multiple fluorescent markers, which could open a door for pathological diagnostics.

  17. Detecting Renibacterium salmoninarum in wild brown trout by use of multiple organ samples and diagnostic methods

    Science.gov (United States)

    Guomundsdottir, S.; Applegate, Lynn M.; Arnason, I.O.; Kristmundsson, A.; Purcell, Maureen K.; Elliott, Diane G.

    2017-01-01

    Renibacterium salmoninarum, the causative agent of salmonid bacterial kidney disease (BKD), is endemic in many wild trout species in northerly regions. The aim of the present study was to determine the optimal R. salmoninarum sampling/testing strategy for wild brown trout (Salmo trutta L.) populations in Iceland. Fish were netted in a lake and multiple organs—kidney, spleen, gills, oesophagus and mid-gut—were sampled and subjected to five detection tests i.e. culture, polyclonal enzyme-linked immunosorbent assay (pELISA) and three different PCR tests. The results showed that each fish had encountered R. salmoninarum but there were marked differences between results obtained depending on organ and test. The bacterium was not cultured from any kidney sample while all kidney samples were positive by pELISA. At least one organ from 92.9% of the fish tested positive by PCR. The results demonstrated that the choice of tissue and diagnostic method can dramatically influence the outcome of R. salmoninarum surveys.

  18. Smoldering (Asymptomatic) Multiple Myeloma: Current Diagnostic Criteria, New Predictors of Outcome, and Follow-Up Recommendations

    Science.gov (United States)

    Bladé, Joan; Dimopoulos, Meletios; Rosiñol, Laura; Rajkumar, S. Vincent; Kyle, Robert A.

    2010-01-01

    Purpose To provide an overview on smoldering (asymptomatic) multiple myeloma (SMM) including current diagnostic criteria, predictors of progression, pattern of progression, and outcome. Design A comprehensive review of the literature on risk factors for progression, treatment attempts to delay progression and outcome in patients with SMM. Results The risk factors for progression of SMM include: plasma cell mass including M-protein size and percentage of bone marrow clonal plasma cells (BMPC), abnormal free light chain ratio, proportion of phenotypically abnormal BMPC, immunoparesis, evolution pattern (evolving v nonevolving), and pattern of magnetic resonance imaging abnormalities. Most patients with SMM progress with anemia and/or skeletal involvement. Immediate therapy with cytotoxic agents, such as melphalan/prednisone has not resulted in improved outcome. Patients should not be treated until progressive disease with end-organ damage occurs. Increasing anemia is the most reliable indicator of progression. Conclusion These recently recognized predictors of outcome may be helpful for better disease monitoring and for investigation of new treatment approaches. Thus, recommendations for follow-up every to 3 to 6 months depending on the risk of progression are suggested, and clinical trials with new noncytotoxic biologically derived agents to delay progression, particularly in high-risk patients, are ongoing. PMID:20026810

  19. Teaching Multidigit Multiplication: Combining Multiple Frameworks to Analyse a Class Episode

    Science.gov (United States)

    Clivaz, Stéphane

    2017-01-01

    This paper provides an analysis of a teaching episode of the multidigit algorithm for multiplication, with a focus on the influence of the teacher's mathematical knowledge on their teaching. The theoretical framework uses Mathematical Knowledge for Teaching, mathematical pertinence of the teacher and structuration of the milieu in a descending and…

  20. Combined analysis of BRAF-gene mutation and galectin-3 expression in preoperative diagnostics of thyroid cancer

    Directory of Open Access Journals (Sweden)

    D Yu Semenov

    2011-06-01

    Full Text Available To assess the utility of combined detection BRAF gene mutation and Gal-3 expression from FNAB specimens in preoperative diagnostic of thyroid gland cancer. 41 patients with thyroid gland nodules were included in the study. By cytological conclusions of evaluated FNA specimens 20 patients had papillar thyroid cancer (PTC, 17 – follicular neoplasia, and 4 – nodular colloid goiter. Gal-3 expression were evaluated by flow cytometry method; BRAF gene mutation were evaluated by PCR. In our study the sensitivity of combined detection BRAF gene mutation and Gal-3 expression was 95%, specificity – 95%, diagnostic accuracy – 95%. Combined detection of BRAF gene mutation by PCR and Gal-3 expression by flow cytometry could be used in preoperative diagnostic of thyroid glad cancer.

  1. What is the added value of combined core biopsy and fine needle aspiration in the diagnostic process of renal tumours?

    Science.gov (United States)

    Barwari, K; Kummerlin, I P; ten Kate, F J; Algaba, F; Trias, I; Wijkstra, H; De la Rosette, J J; Laguna, P

    2013-08-01

    Non-diagnostic results still hinder the routine use of core biopsy (CB) and fine needle aspiration (FNA) in the diagnostic process of renal tumours. Furthermore, substantial interobserver variability has been reported. We assessed the added value of combining the results of CB and FNA by five pathologists in the ex vivo diagnosis of renal mass. Two ex vivo core biopsies were taken followed by two FNA passes from extirpated tumours. All samples were evaluated by five blinded pathologists. A consensus diagnosis of the surgical specimen was the index for comparison. For each pathologist, the number of non-diagnostic (non-conclusive or undetermined biology and failed biopsies), correct and incorrect scored cases of each technique was assessed. When a non-diagnostic CB or FNA had a correct diagnostic counterpart, this was considered as of added value. Of the 57 assessed tumours, 53 were malignant. CB was non-diagnostic in 4-10 cases (7-17.5%). FNA established the correct diagnosis in 1-7 of these cases. FNA was non-diagnostic in 2-6 cases (3.5-10.5%), and the counterpart CB established the correct diagnosis in 1-6 of these cases. For the 5 pathologists, accuracy of CB and FNA varied between 82.5-93% and 89.5-96.5%, respectively. Combination of both types of biopsy resulted in 55-57 correct results (accuracy 96.5-100%), i.e., an increase in accuracy of 3.5-14%. Combining the result of CB and FNA in renal mass biopsy leads to a higher diagnostic accuracy. Recommendations on which technique used should be adapted to local expertise and logistic possibilities.

  2. Multiple SNPs Detection Based on Lateral Flow Assay for Phenylketonuria Diagnostic.

    Science.gov (United States)

    Liu, Xiaonan; Zhang, Chao; Liu, Kewu; Wang, Han; Lu, Chaoxia; Li, Hang; Hua, Kai; Zhu, Juanli; Hui, Wenli; Cui, Yali; Zhang, Xue

    2018-02-16

    Single nucleotide polymorphisms (SNPs) are closely related to genetic diseases, but current SNP detection methods, such as DNA microarrays that include tedious procedures and expensive, sophisticated instruments, are unable to perform rapid SNPs detection in clinical practice, especially for those multiple SNPs related to genetic diseases. In this study, we report a sensitive, low cost, and easy-to-use point-of-care testing (POCT) system formed by combining amplification refractory mutation system (ARMS) polymerase chain reaction with gold magnetic nanoparticles (GMNPs) and lateral flow assay (LFA) noted as the ARMS-LFA system, which allow us to use a uniform condition for multiple SNPs detection simultaneously. The genotyping results can be explained by a magnetic reader automatically or through visual interpretation according to the captured GMNPs probes on the test and control lines of the LFA device. The high sensitivity (the detection limit of 0.04 pg/μL with plasmid) and specificity of this testing system were found through genotyping seven pathogenic SNPs in phenylalanine hydroxylase gene (PAH, the etiological factor of phenylketonuria). This system can also be applied in DNA quantification with a linear range from 0.02 to 2 pg/μL of plasmid. Furthermore, this ARMS-LFA system was applied to clinical trials for screening the seven pathogenic SNPs in PAH of 23 families including 69 individuals. The concordance rate of the genotyping results detected by the ARMS-LFA system was up to 97.8% compared with the DNA sequencing results. This method is a very promising POCT in the detection of multiple SNPs caused by genetic diseases.

  3. Combined Acquisition Technique (CAT) for Neuroimaging of Multiple Sclerosis at Low Specific Absorption Rates (SAR)

    Science.gov (United States)

    Biller, Armin; Choli, Morwan; Blaimer, Martin; Breuer, Felix A.; Jakob, Peter M.; Bartsch, Andreas J.

    2014-01-01

    Purpose To compare a novel combined acquisition technique (CAT) of turbo-spin-echo (TSE) and echo-planar-imaging (EPI) with conventional TSE. CAT reduces the electromagnetic energy load transmitted for spin excitation. This radiofrequency (RF) burden is limited by the specific absorption rate (SAR) for patient safety. SAR limits restrict high-field MRI applications, in particular. Material and Methods The study was approved by the local Medical Ethics Committee. Written informed consent was obtained from all participants. T2- and PD-weighted brain images of n = 40 Multiple Sclerosis (MS) patients were acquired by CAT and TSE at 3 Tesla. Lesions were recorded by two blinded, board-certificated neuroradiologists. Diagnostic equivalence of CAT and TSE to detect MS lesions was evaluated along with their SAR, sound pressure level (SPL) and sensations of acoustic noise, heating, vibration and peripheral nerve stimulation. Results Every MS lesion revealed on TSE was detected by CAT according to both raters (Cohen’s kappa of within-rater/across-CAT/TSE lesion detection κCAT = 1.00, at an inter-rater lesion detection agreement of κLES = 0.82). CAT reduced the SAR burden significantly compared to TSE (pCAT were 29.0 (±5.7) % for the T2-contrast and 32.7 (±21.9) % for the PD-contrast (expressed as percentages of the effective SAR limit of 3.2 W/kg for head examinations). Average SPL of CAT was no louder than during TSE. Sensations of CAT- vs. TSE-induced heating, noise and scanning vibrations did not differ. Conclusion T2−/PD-CAT is diagnostically equivalent to TSE for MS lesion detection yet substantially reduces the RF exposure. Such SAR reduction facilitates high-field MRI applications at 3 Tesla or above and corresponding protocol standardizations but CAT can also be used to scan faster, at higher resolution or with more slices. According to our data, CAT is no more uncomfortable than TSE scanning. PMID:24608106

  4. An effective combination of sanger and next generation sequencing in diagnostics of primary ciliary dyskinesia.

    Science.gov (United States)

    Djakow, Jana; Kramná, Lenka; Dušátková, Lenka; Uhlík, Jiří; Pursiheimo, Juha-Pekka; Svobodová, Tamara; Pohunek, Petr; Cinek, Ondřej

    2016-05-01

    Primary ciliary dyskinesia (PCD) is a multigenic autosomal recessive condition affecting respiratory tract and other organs where ciliary motility is required. The extent of its genetic heterogeneity is remarkable. The aim of the study was to develop a cost-effective pipeline for genetic diagnostics using a combination of Sanger and next generation sequencing (NGS). Data and samples of 33 families with 38 affected subjects with PCD diagnosed in childhood were collected over the territory of the Czech Republic. A panel of 18 PCD causative or candidate genes was implemented into an Illumina TruSeq Custom Amplicon NGS assay, and three ancestral mutations in SPAG1 were screened by conventional Sanger sequencing, which was also used for the confirmation of the NGS results and for the analysis of familial segregation. The causative gene was DNAH5 in 11/33 (33%) probands, SPAG1 in 8/33 (24%), and DNAI1, CCDC40, LRRC6 in one family each. If the high proportion of subjects with bi-allelic ancestral mutations in SPAG1 is corroborated in other Caucasian populations, a simple Sanger sequencing test for these three mutations may serve as an effective pre-screening step, being followed by an NGS panel for other, much larger, PCD genes. We present a combination of Sanger sequencing with an NGS panel for known and candidate PCD genes, implemented in a moderate-size national collection of patients. This strategy has proven to be cost-effective, rapid and reliable, and was able to detect the causative gene in two thirds of our PCD patients. © 2015 Wiley Periodicals, Inc.

  5. Using Robust Variance Estimation to Combine Multiple Regression Estimates with Meta-Analysis

    Science.gov (United States)

    Williams, Ryan

    2013-01-01

    The purpose of this study was to explore the use of robust variance estimation for combining commonly specified multiple regression models and for combining sample-dependent focal slope estimates from diversely specified models. The proposed estimator obviates traditionally required information about the covariance structure of the dependent…

  6. Enhancing Diagnostic Accuracy of aMCI in the Elderly: Combination of Olfactory Test, Pupillary Response Test, BDNF Plasma Level, and APOE Genotype

    Directory of Open Access Journals (Sweden)

    Yuda Turana

    2014-01-01

    Full Text Available Background. Amnestic Mild Cognitive Impairment (aMCI often progresses to Alzheimer’s disease. There are clinical markers and biomarkers to identify the degenerative process in the brain. Objectives. To obtain the diagnostic values of olfactory test, pupillary response to tropicamide 0.01%, BDNF plasma level, and APOE ε4 in diagnosing aMCI. Methods. Cross-sectional, comparative analysis. Results. There were 109 subjects enrolled (aMCI: 51, normal cognition: 58 with age 64 ± 5.54 years. For diagnosing aMCI, cut-off point for the olfactory score was 22% for pupil dilatation response. Low BDNF plasma level was related significantly with olfactory deficits and aMCI (P<0.05. Four of five subjects with homozygote e4 presented with multiple-domain aMCI. This group displayed the lowest means of olfactory score and the highest means of pupillary hypersensitivity response (P<0.0001. Combination of olfactory deficit and pupillary hypersensitivity response in detection of aMCI was beneficial with Sp 91% and PPV 87%. In conjunction with clinical markers, BDNF plasma level and presence of APOE e4+ improved Sp and PPV. Conclusions. Combination of olfactory test and pupillary response test was useful as diagnostic tool in aMCI. In conjunction with clinical markers, low level of BDNF plasma and presence of APOE e4 improved the diagnostic value.

  7. Diagnostic value of combined versus individual MRI parameters in distinguishing adenomatous from non-adenomatous adrenal lesions in cancer patients

    Directory of Open Access Journals (Sweden)

    Sally Emad-Eldin

    2014-09-01

    Conclusion: The most specific predictors for adrenal mass characterization were CSI signal drop and Gd-DTPA enhancement characteristics. Combining the MR parameters did not prove superior to those two individual parameters, however it yielded a valuable diagnostic protocol for distinguishing the adrenal masses, considering that size criterion should not be used as an individual discriminator.

  8. Diagnostic Importance of 3D CT Images in Klippel-Feil Syndrome with Multiple Skeletal Anomalies: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Yuksel, Murvet [Kahramanmaras Sutcu Imam University, Radiology Dept. (Turkey); Karabiber, Hamza [Kahramanmaras Sutcu Imam University Pediatrics Dept. (Turkey); Yuksel, K. Zafer [Kahramanmaras Sutcu Imam University Neuroradiology Dept (Turkey); Parmaksiz, Gonul [Kahramanmaras Sutcu Imam University Pediatrics Dept. (Turkey)

    2005-07-01

    We present here the case of a 12-year-old boy who had Klippel-Feil syndrome with renal, cardiac and multiple skeletal anomalies, and we show the relevent three-dimensional computed tomography images. Our patient had a triple renal pelvis, mitral valve prolapsus, multiple cervical vertebrae fusions, cervical ribs, hypoplasia of the right thumb, spina bifida of L5, lumbalization at the right side of S1 and a sacral curved defect. In this study, we discuss the atypical clinical features and the diagnostic value of three-dimensional CT for evaluating the skeletal anomalies of the Klippel-Feil syndrome cases.

  9. Combining data from multiple monitors in air pollution mortality time series studies

    Science.gov (United States)

    Roberts, Steven

    In community time series studies on the effect of particulate air pollution on mortality, particulate air pollution data are often available from multiple monitors. Published studies have combined the data from the multiple monitors using a simple or trimmed average. In this paper, I describe an alternative method for combining the particulate air pollution data available from multiple monitors. Using time series data from Cook County, Illinois the proposed method yields more meaningful biologically plausible particulate air pollution mortality effect estimates without loss of statistical accuracy and reduces the full set of monitors to a smaller set without loss of information. The proposed monitor combination may be more highly correlated with the average population exposure to particulate air pollution than a simple or trimmed average of the monitors.

  10. Fused Empirical Mode Decomposition and MUSIC Algorithms for Detecting Multiple Combined Faults in Induction Motors

    Directory of Open Access Journals (Sweden)

    D. Camarena-Martinez

    2015-02-01

    Full Text Available Detection of failures in induction motors is one of the most important concerns in industry. An unexpected fault in the induction motors can cause a loss of financial resources and waste of time that most companies cannot afford. The contribution of this paper is a fusion of the Empirical Mode Decomposition (EMD and Multiple Signal Classification (MUSIC methodologies for detection of multiple combined faults which provides an accurate and effective strategy for the motor condition diagnosis.

  11. The Combine Use of Semi-destructive and Non-destructive Methods for Tiled Floor Diagnostics

    Science.gov (United States)

    Štainbruch, Jakub; Bayer, Karol; Jiroušek, Tomáš; Červinka, Josef

    2017-04-01

    The combination of semi-destructive and non-destructive methods was used to asset the conditions of a tiled floor in the historical monument Minaret, situated in the park complex of the Chateau Lednice (South Moravia Region, Czech Republic), before its renovation. Another set of measurements is going to be performed after the conservation works are finished. (The comparison of the results collected during pre- and post-remediation measurements will be known and presented during the General Assembly meeting in Wien.) The diagnostic complex of methods consisted of photogrammetry, resistivity drilling and georadar. The survey was aimed to contour extends of air gaps beneath the tiles and the efficiency of filling gaps by means of injection, consolidation and gluing individual layers. The state chateau Lednice creates a part of the Lednice-Valtice precinct, a UNESCO landmark, and belongs among the greatest historic monuments in Southern Moravia. In the chateau park there is a romantic observation tower in the shape of a minaret built according to the plans of Josef Hardtmuth between 1798-1804. The Minaret has been extensively renovated for many decades including the restoration of mosaic floors from Venetian terazzo. During the static works of the Minaret building between 1999-2000, the mosaic floors in the rooms on the second floor were transferred and put back onto concrete slabs. Specifically, the floor was cut up to tiles and these were glued to square slabs which were then attached to the base plate. The transfer was not successful and the floor restoration was finalized between 2016-2017. The damage consisted in separating the original floor from the concrete plate which led to creating gaps. Furthermore, the layers of the floor were not compact. It was necessary to fill the gaps and consolidate and glue the layers. The existence of air gap between individual layers of the tiles and their degradation was detected using two different diagnostic methods: semi

  12. Combining multiple algorithms for road network tracking from multiple source remotely sensed imagery: a practical system and performance evaluation.

    Science.gov (United States)

    Lin, Xiangguo; Liu, Zhengjun; Zhang, Jixian; Shen, Jing

    2009-01-01

    In light of the increasing availability of commercial high-resolution imaging sensors, automatic interpretation tools are needed to extract road features. Currently, many approaches for road extraction are available, but it is acknowledged that there is no single method that would be successful in extracting all types of roads from any remotely sensed imagery. In this paper, a novel classification of roads is proposed, based on both the roads' geometrical, radiometric properties and the characteristics of the sensors. Subsequently, a general road tracking framework is proposed, and one or more suitable road trackers are designed or combined for each type of roads. Extensive experiments are performed to extract roads from aerial/satellite imagery, and the results show that a combination strategy can automatically extract more than 60% of the total roads from very high resolution imagery such as QuickBird and DMC images, with a time-saving of approximately 20%, and acceptable spatial accuracy. It is proven that a combination of multiple algorithms is more reliable, more efficient and more robust for extracting road networks from multiple-source remotely sensed imagery than the individual algorithms.

  13. Reducing the computational requirements for simulating tunnel fires by combining multiscale modelling and multiple processor calculation

    DEFF Research Database (Denmark)

    Vermesi, Izabella; Rein, Guillermo; Colella, Francesco

    2017-01-01

    in FDS version 6.0, a widely used fire-specific, open source CFD software. Furthermore, it compares the reduction in simulation time given by multiscale modelling with the one given by the use of multiple processor calculation. This was done using a 1200m long tunnel with a rectangular cross...... processor calculation (97% faster when using a single mesh and multiscale modelling; only 46% faster when using the full tunnel and multiple meshes). In summary, it was found that multiscale modelling with FDS v.6.0 is feasible, and the combination of multiple meshes and multiscale modelling was established...

  14. Robust Distant Speech Recognition by Combining Multiple Microphone-Array Processing with Position-Dependent CMN

    Directory of Open Access Journals (Sweden)

    Wang Longbiao

    2006-01-01

    Full Text Available We propose robust distant speech recognition by combining multiple microphone-array processing with position-dependent cepstral mean normalization (CMN. In the recognition stage, the system estimates the speaker position and adopts compensation parameters estimated a priori corresponding to the estimated position. Then the system applies CMN to the speech (i.e., position-dependent CMN and performs speech recognition for each channel. The features obtained from the multiple channels are integrated with the following two types of processings. The first method is to use the maximum vote or the maximum summation likelihood of recognition results from multiple channels to obtain the final result, which is called multiple-decoder processing. The second method is to calculate the output probability of each input at frame level, and a single decoder using these output probabilities is used to perform speech recognition. This is called single-decoder processing, resulting in lower computational cost. We combine the delay-and-sum beamforming with multiple-decoder processing or single-decoder processing, which is termed multiple microphone-array processing. We conducted the experiments of our proposed method using a limited vocabulary (100 words distant isolated word recognition in a real environment. The proposed multiple microphone-array processing using multiple decoders with position-dependent CMN achieved a 3.2% improvement (50% relative error reduction rate over the delay-and-sum beamforming with conventional CMN (i.e., the conventional method. The multiple microphone-array processing using a single decoder needs about one-third the computational time of that using multiple decoders without degrading speech recognition performance.

  15. A noninvasive multi-analyte diagnostic assay: combining protein and DNA markers to stratify bladder cancer patients

    Directory of Open Access Journals (Sweden)

    Shuber AP

    2012-03-01

    Full Text Available Cecilia A Fernandez1, John M Millholland1, Ellen C Zwarthoff2, Adam S Feldman3, R Jeffrey Karnes4, Anthony P Shuber11Predictive Biosciences, Inc, Lexington, MA, USA; 2Erasmus Medical Center, Rotterdam, The Netherlands; 3Massachusetts General Hospital, Boston, MA, 4Mayo Clinic, Rochester, MN, USAPurpose: The authors recently reported the development of a noninvasive diagnostic assay using urinary matrix metalloproteinases (MMPs as monitors of disease-free status and bladder cancer in high-risk populations. Using an approach called clinical intervention determining diagnostic (CIDD, they identified with high confidence those patients who could be excluded from additional intervention. To maximize performance, MMPs were combined with DNA-based markers and CIDD was applied to a population of patients undergoing monitoring for recurrence.Patients and methods: Urine samples were obtained from 323 patients, 48 of whom had a recurrence and 275 of whom did not have cancer upon cytoscopic evaluation. Twist1 and Nid2 methylation status was determined using methylation-specific polymerase chain reaction, FGFR3 mutational status by quantitative PCR, and MMP levels by enzyme-linked immunosorbent assay.Results: Using a combination of these DNA and protein markers, the authors identified with high confidence (97% negative predicted value those patients who do not have cancer. Cutoffs were adjusted such that at 92% sensitivity, 51% of disease-free patients might be triaged from receiving further tests.Conclusion: The multi-analyte diagnostic readout assay described here is the first to combine protein and DNA biomarkers into one assay for optimal clinical performance. Using this approach, the detection of FGFR3 mutations and Twist1 and Nid2 methylation in the urine of patients undergoing bladder cancer recurrence screening increase the sensitivity and negative predictive value at an established MMP protein cutoff. This noninvasive urinary diagnostic assay could

  16. Diagnostic accuracy of full-body linear X-ray scanning in multiple trauma patients in comparison to computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Joeres, A.P.W.; Heverhagen, J.T.; Bonel, H. [Inselspital - University Hospital Bern (Switzerland). Univ. Inst. of Diagnostic, Interventional and Pediatric Radiology; Exadaktylos, A. [Inselspital - University Hospital Bern (Switzerland). Dept. of Emergency Medicine; Klink, T. [Inselspital - University Hospital Bern (Switzerland). Univ. Inst. of Diagnostic, Interventional and Pediatric Radiology; Wuerzburg Univ. (Germany). Inst. of Diagnostic and Interventional Radiology

    2016-02-15

    The purpose of this study was to evaluate the diagnostic accuracy of full-body linear X-ray scanning (LS) in multiple trauma patients in comparison to 128-multislice computed tomography (MSCT). 106 multiple trauma patients (female: 33; male: 73) were retrospectively included in this study. All patients underwent LS of the whole body, including extremities, and MSCT covering the neck, thorax, abdomen, and pelvis. The diagnostic accuracy of LS for the detection of fractures of the truncal skeleton and pneumothoraces was evaluated in comparison to MSCT by two observers in consensus. Extremity fractures detected by LS were documented. The overall sensitivity of LS was 49.2%, the specificity was 93.3%, the positive predictive value was 91%, and the negative predictive value was 57.5%. The overall sensitivity for vertebral fractures was 16.7%, and the specificity was 100%. The sensitivity was 48.7% and the specificity 98.2% for all other fractures. Pneumothoraces were detected in 12 patients by CT, but not by LS.40 extremity fractures were detected by LS, of which 4 fractures were dislocated, and 2 were fully covered by MSCT. The diagnostic accuracy of LS is limited in the evaluation of acute trauma of the truncal skeleton. LS allows fast whole-body X-ray imaging, and may be valuable for detecting extremity fractures in trauma patients in addition to MSCT.

  17. Generalizability of Diagnostic-Prescriptive Teaching Strategies across Student Locus of Control and Multiple Instructional Units.

    Science.gov (United States)

    Benson, Jean S.; Yeany, Russell H.

    Reported is a study that explores the effect on student achievement of diagnostic-prescriptive instructional strategies on preservice elementary education majors (N=43) enrolled in an introductory biology course. Factors of pre-treatment achievement and locus of control were analyzed as well. Units on Mendelian genetics, modern genetics, and…

  18. The Diagnostic importance of clinical and radiologic features of the Multiple Cemento-osseous dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Han, M. R.; Kim, Y. H.; Kang, B. C. [College of Dentistry, Chonam National University, Kwangju (Korea, Republic of)

    1998-02-15

    This case was diagnosed as multiple cementoosseous dysplasia on the basis of clinical and radiological features but was diagnosed as ossifying fibroma on the basis of histopathological feature. The histopathologic features of the multiple cementoosseous dysplasia and cementoossifying fibroma have common features of cementum, fibrous network and bone. Multiple cementoosseous dysplasia is reactive lesion and shows restricted lesion size, occurred on anterior and posterior tooth of the mandible and needs no treatment except periodic follow up. But Cementoossifying fibroma is the true neoplasm and grows continuously and needs surgical removal. The final diagnosis of the multiple cementoosseous dysplasia requires good correlation of the clinical histopathological, and radiological features.

  19. The combined use of conventional MRI and MR spectroscopic imaging increases the diagnostic accuracy in amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cervo, Amedeo [Department of Advanced Biomedical Sciences, University “Federico II”, Naples (Italy); Cocozza, Sirio, E-mail: siriococozza@hotmail.it [Department of Advanced Biomedical Sciences, University “Federico II”, Naples (Italy); Saccà, Francesco [Department of Neurosciences, Reproductive Sciences and Odontostomatology, University “Federico II”, Naples (Italy); Giorgio, Sara M.d.A. [Department of Advanced Biomedical Sciences, University “Federico II”, Naples (Italy); Morra, Vincenzo Brescia [Department of Neurosciences, Reproductive Sciences and Odontostomatology, University “Federico II”, Naples (Italy); Tedeschi, Enrico [Department of Advanced Biomedical Sciences, University “Federico II”, Naples (Italy); Marsili, Angela; Vacca, Giovanni [Department of Neurosciences, Reproductive Sciences and Odontostomatology, University “Federico II”, Naples (Italy); Palma, Vincenzo [U.O.C. Neurofisiopatologia, PO S. Gennaro ASL Napoli 1, Naples (Italy); Brunetti, Arturo [Department of Advanced Biomedical Sciences, University “Federico II”, Naples (Italy); Quarantelli, Mario [Biostructure and Bioimaging Institute, National Research Council, Naples (Italy)

    2015-01-15

    Highlights: • We assessed in ALS the diagnostic accuracy of MRI signal and MRS data used alone and in combination. • We found that T2-hypointensity and NAA decrease in motor cortex are two independent phenomena. • These two variables taken alone do not provide acceptable diagnostic accuracy in ALS. • The same variables, when used in combination, improve the diagnostic accuracy of MRI in ALS. - Abstract: Purpose: We aimed to assess, in amyotrophic lateral sclerosis (ALS), the diagnostic accuracy of the combined use of conventional MRI signal changes (namely, hypointensity of the precentral cortex and hyperintensity of the corticospinal tracts on T2-weighted images), and N-Acetyl-Aspartate (NAA) reduction in the motor cortex at Magnetic Resonance Spectroscopy (MRS), which are affected by limited diagnostic accuracy when used separately. Methods: T2-hypointensity and NAA/(Choline + Creatine) ratio of the precentral gyrus and T2-hyperintensity of the corticospinal tracts were measured in 84 ALS patients and 28 healthy controls, using a Region-of-Interest approach. Sensitivity and specificity values were calculated using Fisher stepwise discriminant analysis, and cross-validated using the leave-one-out method. Results: Precentral gyrus T2 signal intensity (p < 10{sup −4}) and NAA peak (p < 10{sup −6}) were significantly reduced in patients, and their values did not correlate significantly to each other both in patients and controls, while no significant differences were obtained in terms of T2-hyperintensity of the corticospinal tract. Sensitivity and specificity of the two discriminant variables, taken alone, were 71.4% and 75.0%, for NAA peak, and 63.1% and 71.4% for T2-hypointensity, respectively. When using these two variables in combination, a significant increase in sensitivity (78.6%) and specificity (82.1%) was achieved. Conclusions: Precentral gyrus T2-hypointensity and NAA peak are not significantly correlated in ALS patients, suggesting that they

  20. Speckle-based hyperspectral imaging combining multiple scattering and compressive sensing in nanowire mats

    OpenAIRE

    Muskens, Otto; French, Rebecca; Gigan, Sylvain

    2017-01-01

    Dataset containing measurement and simulation results in ascii format, including matlab figures.Dataset supports: French, R., Gigan, S., & Muskens, O. L. (2017). Speckle-based hyperspectral imaging combining multiple scattering and compressive sensing in nanowire mats. Optics Letters, 42(9), 1820.

  1. Association analysis of multiple traits by an approach of combining P ...

    Indian Academy of Sciences (India)

    Administrator

    Association analysis of multiple traits by an approach of combining P-values. LILI CHEN1,2,*, YONG WANG1, YAJING ZHOU2. 1 Department of Mathematics, School of Sciences, Harbin Institute of Technology,Harbin. 150001,P. R. China;. 2 Department of Statistics, School of Mathematical Sciences, Heilongjiang University ...

  2. O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas.

    Science.gov (United States)

    Pauleit, Dirk; Floeth, Frank; Hamacher, Kurt; Riemenschneider, Markus J; Reifenberger, Guido; Müller, Hans-Wilhelm; Zilles, Karl; Coenen, Heinz H; Langen, Karl-Josef

    2005-03-01

    MRI is commonly used to determine the location and extent of cerebral gliomas. We investigated whether the diagnostic accuracy of MRI could be improved by the additional use of PET with the amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (FET). In a prospective study, PET with FET and MRI was performed in 31 patients with suspected cerebral gliomas. PET and MRIs were co-registered and 52 neuronavigated tissue biopsies were taken from lesions with both abnormal MRI signal and increased FET uptake (match), as well as from areas with abnormal MR signal but normal FET uptake or vice versa (mismatch). Biopsy sites were labelled by intracerebral titanium pellets. The diagnostic performance for the identification of cellular tumour tissue was analysed for either MRI alone or MRI combined with FET PET using alternative free response receiver operating characteristic curves (ROCs). Histologically, 26 biopsy samples corresponded to cellular glioma tissue and 26 to peritumoral brain tissue. The diagnostic performance, as determined by the area under the ROC curve (Az), was Az = 0.80 for MRI alone and Az = 0.98 for the combined MRI and FET PET approach (P < 0.001). MRI yielded a sensitivity of 96% for the detection of tumour tissue but a specificity of only 53%, and combined use of MRI and FET PET yielded a sensitivity of 93% and a specificity of 94%. Combined use of MRI and FET PET in patients with cerebral gliomas significantly improves the identification of cellular glioma tissue and allows definite histological tumour diagnosis. Thus, our findings may have considerable impact on target selection for diagnostic biopsies as well as therapy planning.

  3. A Diagnostic Study of Pre-Service Teachers' Competency in Multiple-Choice Item Development

    Science.gov (United States)

    Asim, Alice E.; Ekuri, Emmanuel E.; Eni, Eni I.

    2013-01-01

    Large class size is an issue in testing at all levels of Education. As a panacea to this, multiple choice test formats has become very popular. This case study was designed to diagnose pre-service teachers' competency in constructing questions (IQT); direct questions (DQT); and best answer (BAT) varieties of multiple choice items. Subjects were 88…

  4. Multiple shRNA combinations for near-complete coverage of all HIV-1 strains

    Directory of Open Access Journals (Sweden)

    Tran Anna

    2011-01-01

    Full Text Available Abstract Background Combinatorial RNA interference (co-RNAi approaches are needed to account for viral variability in treating HIV-1 with RNAi, as single short hairpin RNAs (shRNA are rapidly rendered ineffective by resistant strains. Current work suggests that 4 simultaneously expressed shRNAs may prevent the emergence of resistant strains. Results In this study we assembled combinations of highly-conserved shRNAs to target as many HIV-1 strains as possible. We analyzed intersecting conservations of 10 shRNAs to find combinations with 4+ matching the maximum number of strains using 1220+ HIV-1 sequences from the Los Alamos National Laboratory (LANL. We built 26 combinations of 2 to 7 shRNAs with up to 87% coverage for all known strains and 100% coverage of clade B subtypes, and characterized their intrinsic suppressive activities in transient expression assays. We found that all combinations had high combined suppressive activities, though there were also large changes in the individual activities of the component shRNAs in our multiple expression cassette configurations. Conclusion By considering the intersecting conservations of shRNA combinations we have shown that it is possible to assemble combinations of 6 and 7 highly active, highly conserved shRNAs such that there is always at least 4 shRNAs within each combination covering all currently known variants of entire HIV-1 subtypes. By extension, it may be possible to combine several combinations for complete global coverage of HIV-1 variants.

  5. Combination of fast-ion diagnostics in velocity-space tomographies

    DEFF Research Database (Denmark)

    Salewski, Mirko; Geiger, B.; Nielsen, Stefan Kragh

    2013-01-01

    Fast-ion Dα (FIDA) and collective Thomson scattering (CTS) diagnostics provide indirect measurements of fast-ion velocity distribution functions in magnetically confined plasmas. Here we present the first prescription for velocity-space tomographic inversion of CTS and FIDA measurements that can ...

  6. Combination of fast-ion diagnostics in velocity-space tomographies

    NARCIS (Netherlands)

    Salewski, M.; Geiger, B.; Nielsen, S.K.; Bindslev, H.; M. García-Muñoz,; Heidbrink, W. W.; Korsholm, S. B.; Leipold, F.; Madsen, J.; Meo, F.; Michelsen, P. K.; Moseev, D.; Stejner, M.; Tardini, G.; ASDEX Upgrade team,

    2013-01-01

    Fast-ion D α (FIDA) and collective Thomson scattering (CTS) diagnostics provide indirect measurements of fast-ion velocity distribution functions in magnetically confined plasmas. Here we present the first prescription for velocity-space tomographic inversion of CTS and FIDA measurements that can

  7. Two-Step Robust Diagnostic Method for Identification of Multiple High Leverage Points

    OpenAIRE

    Arezoo Bagheri; Habshah Midi; A. H.M.R. Imon

    2009-01-01

    Problem statement: High leverage points are extreme outliers in the X-direction. In regression analysis, the detection of these leverage points becomes important due to their arbitrary large effects on the estimations as well as multicollinearity problems. Mahalanobis Distance (MD) has been used as a diagnostic tool for identification of outliers in multivariate analysis where it finds the distance between normal and abnormal groups of the data. Since the computation of MD relies on non-robus...

  8. Interacting multiple-models, state augmented Particle Filtering for fault diagnostics

    OpenAIRE

    Compare, Michele; Baraldi, Piero; Turati, Pietro; Zio, Enrico

    2015-01-01

    International audience; Particle Filtering (PF) is a model-based, filtering technique, which has drawn the attention of the Prognostic and Health Management (PHM) community due to its applicability to nonlinear models with non-additive and non-Gaussian noise. When multiple physical models can describe the evolution of the degradation of a component, the PF approach can be based on Multiple Swarms (MS) of particles, each one evolving according to a different model, from which to select the mos...

  9. Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bortezomib and dexamethasone.

    Science.gov (United States)

    López-Iglesias, Ana-Alicia; González-Méndez, Lorena; San-Segundo, Laura; Herrero, Ana B; Hernández-García, Susana; Martín-Sánchez, Montserrat; Gutiérrez, Norma C; Paíno, Teresa; Avilés, Pablo; Mateos, María-Victoria; San-Miguel, Jesús F; Garayoa, Mercedes; Ocio, Enrique M

    2017-01-01

    Despite new advances in multiple myeloma treatment and the consequent improvement in overall survival, most patients relapse or become refractory to treatment. This suggests that new molecules and combinations that may further inhibit important survival pathways for these tumor cells are needed. In this context, zalypsis is a novel compound, derived from marine organisms, with a powerful preclinical anti-myeloma effect based on the sensitivity of malignant plasma cells to DNA-damage induction; and it has already been tested in a phase I/II clinical trial in multiple myeloma. We hypothesized that the addition of this compound to the combination of bortezomib plus dexamethasone may improve efficacy with acceptable toxicity. The triple combination demonstrated strong synergy and higher efficacy compared with double combinations; not only in vitro, but also ex vivo and, especially, in in vivo experiments. The triple combination triggers cell death, mainly through a synergistic induction of DNA damage and a decrease in the nuclear localization of nuclear factor kappa B. Our findings support the clinical evaluation of this combination for relapsed and refractory myeloma patients. Copyright© Ferrata Storti Foundation.

  10. [Rapid analysis on phenolic compounds in Rheum palmatum based on UPLC-Q-TOF/MSE combined with diagnostic ions filter].

    Science.gov (United States)

    Wang, Qing; Lu, Zhi-Wei; Liu, Yue-Hong; Wang, Ming-Ling; Fu, Shuang; Zhang, Qing-Qing; Zhao, Hui-Zhen; Zhang, Zhi-Xin; Xie, Zi-Ye; Huang, Zheng-Hai; Yu, Hong-Hong; Zhou, Wen-Juan; Gao, Xiao-Yan

    2017-05-01

    Diagnostic ions filter method was used to rapidly detect and identify the phenolic compounds in Rheum palmatum based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). The representative authentic standards of phenolic compounds, including gallic acid, (+)-catechin, (-)-epicatechin, (-)-epicatechin-3-O-gallate and procyanidin B2, were subjected to analysis by UPLC-Q-TOF/MSE system with negative ion mode. Fragmentation patterns of each standard were summarized based on assigned fragment ions. The prominent product ions were selected as diagnostic ions. Subsequently, diagnostic ions filter was employed to rapidly recognize analogous skeletons. Combined with retention time, accurate mass, characteristic fragments and previous literature data, the structures of the filtered compounds were identified or tentatively characterized. A total 63 phenolic compounds (36 phenolic acid derivatives, 8 flavonoid derivatives and 19 tennis derivatives) in R. palmatum were identified, including 6 potential new compounds. The method of diagnostic ions filter could rapidly detect and identify phenolic compounds in R. palmatum This study provides a method for rapid detection of phenolic compounds in R. palmatum and is expected to complete the material basis of rhubarb. Copyright© by the Chinese Pharmaceutical Association.

  11. THE SEARCH OF OPTIMAL COMBINATION OF ANTIGENS FOR SEROLOGICAL DIAGNOSTICS OF TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    E. V. Vasilyeva

    2013-01-01

    Full Text Available Abstract. The four chimeric recombinant antigens CBD-CFP10, CBD-ESAT6, ESAT6-CFP10 and CBD-P38 contained aminoacid sequences of full-size proteins ESAT6, CFP10 and matured protein P38 of M. tuberculosis, joined with aminoacid sequences of cellulose bind domain of endogluconase A (CBD from Cellumonas fimi have been obtained by gene engineering methods. Recombinant proteins were purified by affine chromatography in column with Ni-NTA-sepharose 6В-CL and as PPDN-3 were used for detection of their antigenic activity in indirect ELISA for TB serological diagnostics. The sera from patients with lung tuberculosis (n = 321, from persons who had professional contacts with TB patients (n = 42, from healthy blood donors (n = 366 and from patients with lung diseases of non-TB etiology were tested. It was detected that there was positive correlation between antibodies level for all studied antigens compared by pair. It has been demonstrated that although antigens were different by antigenic and immunobiological characteristics they add each other in the content of antigenic diagnostics compositions. Thus, all these antigens can be used in the test kits for serological diagnostics of TB. Using of these antigens will allow to detect persons infected by TB and patients with active tuberculosis. 

  12. [Diagnostic medical error as an overinterpretation of toxicology screening combined with inadequate clinical assessment].

    Science.gov (United States)

    Kłys, Małgorzata; Kowalski, Piotr

    2011-01-01

    Problems of patient safety within the system of health care are defined by prescriptive and ethical regulations; a breach of such regulations is associated with entering a complex category of situations covered by the term "medical error" or "appropriateness of medical management". In order to minimize the sources of diagnostic errors, with the knowledge on such errors largely originating from medico-legal practice, numerous initiatives emerge, according to which monitoring of adverse events and subjecting such events to a profound discussion is the most important element of prevention. The problem discussed in the paper is illustrated by the case of a 13-year old boy, in whom opioid poisoning was mistakenly diagnosed instead of a neurological condition in consequence of the physician disregarding significant symptoms of the disease and accepting his subjective suspicion of poisoning. The erroneous diagnosis was further compounded by lack of verification of the preliminary diagnosis and failure to perform further laboratory diagnostic management addressing the neurological status of the patient. The presented case supports data from publications found in the literature on the subject that describe a high risk of diagnostics errors in neurological conditions; such errors are often committed by emergency physicians other than neurologists.

  13. New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Cortinas, Inés Vidal, E-mail: invi@montevideo.com.uy; Beretta, Mario; Alonso, Omar; Mut, Fernando [Departamento de Medicina Nuclear do Hospital ‘Asociación Española’, Br. Artigas 1515, Montevideo (Uruguay)

    2015-08-15

    Myocardial perfusion scintigraphy (MPS) in patients not reaching 85% of the maximum predicted heart rate (MPHR) has reduced sensitivity. In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP) was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols. In patients not reaching a sufficient exercise (SE) test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection. Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR) and 67 underwent the dipyridamole alone test (DIP). They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43). For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35). Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001). The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP.

  14. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality

    DEFF Research Database (Denmark)

    Thormann, Anja; Sorensen, Per Soelberg; Koch-Henriksen, Nils

    2017-01-01

    OBJECTIVE: To investigate the effect of chronic comorbidity on the time of diagnosis of multiple sclerosis (MS) and on mortality in MS. METHODS: We conducted a population-based, nationwide cohort study including all incident MS cases in Denmark with first MS symptom between 1980 and 2005. To inve......OBJECTIVE: To investigate the effect of chronic comorbidity on the time of diagnosis of multiple sclerosis (MS) and on mortality in MS. METHODS: We conducted a population-based, nationwide cohort study including all incident MS cases in Denmark with first MS symptom between 1980 and 2005...

  15. Multiple testing procedures for identifying desirable dose combinations in bifactorial designs

    Directory of Open Access Journals (Sweden)

    Buchheister, Bettina

    2006-06-01

    Full Text Available Hung, Chi, and Lipicky proposed the AVE and MAX tests to analyse in a bifactorial design whether combinations of two drugs at several doses fulfil the desirable property of superiority to both their single drug components. These are global tests and do not identify the special combinations which are more effective than their respective single components. Here multiple testing procedures based on linear contrast tests and on the closed testing principle will be presented. They will be compared with simultaneous Min tests of Laska and Meisner. The performance of these approaches is investigated by simulation studies.

  16. Combination of diagnostic medial calcaneal nerve block followed by pulsed radiofrequency for plantar fascitis pain: A new modality.

    Science.gov (United States)

    Thapa, Deepak; Ahuja, Vanita

    2014-03-01

    Plantar fasciitis (PF) is the most common cause of chronic heel pain which may be bilateral in 20 to 30% of patients. It is a very painful and disabling condition which can affect the quality of life. The management includes both pharmacological and operative procedures with no single proven effective treatment modality. In the present case series, we managed three patients with PF (one with bilateral PF). Following a diagnostic medial calcaneal nerve (MCN) block at its origin, we observed reduction in verbal numerical rating scale (VNRS) in all the three patients. Two patients has relapse of PF pain which was managed with MCN block followed with pulsed radio frequency (PRF). All the patients were pain-free at the time of reporting. This case series highlights the possible role of combination of diagnostic MCN block near its origin followed with PRF as a new modality in management of patients with PF.

  17. Combination of diagnostic medial calcaneal nerve block followed by pulsed radiofrequency for plantar fascitis pain: A new modality

    Directory of Open Access Journals (Sweden)

    Deepak Thapa

    2014-01-01

    Full Text Available Plantar fasciitis (PF is the most common cause of chronic heel pain which may be bilateral in 20 to 30% of patients. It is a very painful and disabling condition which can affect the quality of life. The management includes both pharmacological and operative procedures with no single proven effective treatment modality. In the present case series, we managed three patients with PF (one with bilateral PF. Following a diagnostic medial calcaneal nerve (MCN block at its origin, we observed reduction in verbal numerical rating scale (VNRS in all the three patients. Two patients has relapse of PF pain which was managed with MCN block followed with pulsed radio frequency (PRF. All the patients were pain-free at the time of reporting. This case series highlights the possible role of combination of diagnostic MCN block near its origin followed with PRF as a new modality in management of patients with PF.

  18. Diagnostic Performance of Wells Score Combined With Point-of-care Lung and Venous Ultrasound in Suspected Pulmonary Embolism.

    Science.gov (United States)

    Nazerian, Peiman; Volpicelli, Giovanni; Gigli, Chiara; Becattini, Cecilia; Papa, Giuseppe Francesco Sferrazza; Grifoni, Stefano; Vanni, Simone

    2017-03-01

    Lung and venous ultrasound are bedside diagnostic tools increasingly used in the early diagnostic approach of suspected pulmonary embolism (PE). However, the possibility of improving the conventional prediction rule for PE by integrating ultrasound has never been investigated. We performed lung and venous ultrasound in consecutive patients suspected of PE in four emergency departments. Conventional Wells score (Ws) was adjudicated by the attending physician, and ultrasound was performed by one of 20 investigators. Signs of deep venous thrombosis (DVT) at venous ultrasound and signs of pulmonary infarcts or alternative diagnoses at lung ultrasound were considered to recalculate two items of the Ws: signs and symptoms of DVT and alternative diagnosis less likely than PE. The diagnostic performances of the ultrasound-enhanced Ws (USWs) and Ws were then compared after confirmation of the final diagnosis. A total of 446 patients were studied. PE was confirmed in 125 patients (28%). USWs performed significantly better than Ws, with a sensitivity of 69.6% versus 57.6% and a specificity of 88.2% versus 68.2%. In combination with D-dimer, USWs showed an optimal failure rate (0.8%) and a significantly superior efficiency than Ws (32.3% vs. 27.2%). A strategy based on lung and venous ultrasound combined with D-dimer would allow to avoid CT pulmonary angiography in 50.5% of patients with suspected PE, compared to 27.2% when the rule without ultrasound is applied. A pretest risk stratification enhanced by ultrasound of lung and venous performs better than Ws in the early diagnostic process of PE. © 2016 by the Society for Academic Emergency Medicine.

  19. A calderón multiplicative preconditioner for the combined field integral equation

    KAUST Repository

    Bagci, Hakan

    2009-10-01

    A Calderón multiplicative preconditioner (CMP) for the combined field integral equation (CFIE) is developed. Just like with previously proposed Caldern-preconditioned CFIEs, a localization procedure is employed to ensure that the equation is resonance-free. The iterative solution of the linear system of equations obtained via the CMP-based discretization of the CFIE converges rapidly regardless of the discretization density and the frequency of excitation. © 2009 IEEE.

  20. Use of combination therapy with immunomodulators and immunosuppressants in treating multiple sclerosis.

    Science.gov (United States)

    Jeffery, Douglas R

    2004-12-28

    Immunomodulating agents have beneficial effects in the treatment of multiple sclerosis (MS), decreasing the frequency of relapses, the progression of disability, and MRI measures of disease activity. Despite the efficacy of these agents, many patients continue to show progression of disability, breakthrough relapses, and active disease on MRI. Therefore, clinicians have employed a variety of combinations of agents in an attempt to decrease disease activity in those with active disease despite standard immunomodulatory therapy. Although a variety of combination therapies have been used in clinical practice, there is a paucity of data available to guide clinical decision-making. A major pitfall in using combination therapy in the absence of data demonstrating safety is the possibility that the agent added to the primary therapy may have no effect or, worse, may antagonize the effect of the primary agent. The combination of mitoxantrone and interferon beta (IFNbeta) appears safe in short-term studies from a toxicity standpoint and is associated with a reduction in relapse rates, a decrease in the frequency of enhancing lesions, and a decrease in T2 lesion burden. Other combinations that appear safe in preliminary studies include IFNbeta-1a and methotrexate, IFNbeta-1a and azathioprine, and mitoxantrone plus methylprednisolone. The decision to use combination therapy in patients with a suboptimal response to monotherapy should be considered early and not be delayed until disability becomes advanced. This review discusses the available data regarding the combination of standard immunomodulatory therapy with immunosuppressive agents.

  1. Combined Dynamic Time Warping with Multiple Sensors for 3D Gesture Recognition

    Science.gov (United States)

    2017-01-01

    Cyber-physical systems, which closely integrate physical systems and humans, can be applied to a wider range of applications through user movement analysis. In three-dimensional (3D) gesture recognition, multiple sensors are required to recognize various natural gestures. Several studies have been undertaken in the field of gesture recognition; however, gesture recognition was conducted based on data captured from various independent sensors, which rendered the capture and combination of real-time data complicated. In this study, a 3D gesture recognition method using combined information obtained from multiple sensors is proposed. The proposed method can robustly perform gesture recognition regardless of a user’s location and movement directions by providing viewpoint-weighted values and/or motion-weighted values. In the proposed method, the viewpoint-weighted dynamic time warping with multiple sensors has enhanced performance by preventing joint measurement errors and noise due to sensor measurement tolerance, which has resulted in the enhancement of recognition performance by comparing multiple joint sequences effectively. PMID:28817094

  2. Combined Dynamic Time Warping with Multiple Sensors for 3D Gesture Recognition.

    Science.gov (United States)

    Choi, Hyo-Rim; Kim, TaeYong

    2017-08-17

    Cyber-physical systems, which closely integrate physical systems and humans, can be applied to a wider range of applications through user movement analysis. In three-dimensional (3D) gesture recognition, multiple sensors are required to recognize various natural gestures. Several studies have been undertaken in the field of gesture recognition; however, gesture recognition was conducted based on data captured from various independent sensors, which rendered the capture and combination of real-time data complicated. In this study, a 3D gesture recognition method using combined information obtained from multiple sensors is proposed. The proposed method can robustly perform gesture recognition regardless of a user's location and movement directions by providing viewpoint-weighted values and/or motion-weighted values. In the proposed method, the viewpoint-weighted dynamic time warping with multiple sensors has enhanced performance by preventing joint measurement errors and noise due to sensor measurement tolerance, which has resulted in the enhancement of recognition performance by comparing multiple joint sequences effectively.

  3. Biatrial myxoma and multiple organ infarctions combined with Leriche syndrome in a female patient.

    Science.gov (United States)

    Min, Seung Yeon; Lim, Young-Hyo; Lee, Hyung Tak; Shin, Jinho; Kim, Kyung-Soo; Kim, Hyuck

    2014-12-05

    Multiple organ infarctions combined with Leriche syndrome due to embolic particles of myxoma are very rare. There is no definite guideline for immediate medical treatment. A 36-year-old married female was referred to the emergency department (ED) with severe pain of both lower extremities and gradual decreased mental status. Brain magnetic resonance imaging (MRI) and computed tomography angiography (CTA) revealed acute multiple organ infarctions including the brain, spleen, and bilateral kidneys combined with Leriche syndrome. To evaluate the embolic source, echocardiography was performed and it revealed biatrial myxoma. Because of the risk of progression in systemic embolic events, surgical excision and embolectomy were performed urgently. After the operation, renal function was recovered, and the pain of both limbs was relieved. However, the visual field defect due to the brain infarction remained. She was discharged uneventfully on the fourteenth postoperative day. This was an extremely rare case of multiple organ infarctions combined with Leriche syndrome as the initial presentation of biatrial myxoma. The treatment of choice for myxoma is surgical excision, but the optimal timing of operations is still controversial in patients who have had recent neurological insults. Echocardiography was useful to clarify the diagnosis and decide on the proper treatment modality: surgical treatment or thrombolysis.

  4. Generalizability of diagnostic-prescriptive teaching strategies across student locus of control and multiple instructional units

    Science.gov (United States)

    Benson, Jean S.; Yeany, Russell H.

    The influence of locus of control and diagnostic testing with prescribed remediation on immediate and retained science achievement was the focus of the study. To test the generalizability of the results across instructional units and to check on the existence of a treatment warm-up period, the experiment was conducted across three biology units. The results supported the existence of the warm-up period with no significant effects of diagnosis and remediation during the first unit. On later units and on the retention measure, the experimental subjects achieved significantly more than the control. No locus of control X treatment interactions were found; although, in one unit, the internal locus of control subjects achieved significantly higher than externals.

  5. A simple method for combining genetic mapping data from multiple crosses and experimental designs.

    Directory of Open Access Journals (Sweden)

    Jeremy L Peirce

    Full Text Available BACKGROUND: Over the past decade many linkage studies have defined chromosomal intervals containing polymorphisms that modulate a variety of traits. Many phenotypes are now associated with enough mapping data that meta-analysis could help refine locations of known QTLs and detect many novel QTLs. METHODOLOGY/PRINCIPAL FINDINGS: We describe a simple approach to combining QTL mapping results for multiple studies and demonstrate its utility using two hippocampus weight loci. Using data taken from two populations, a recombinant inbred strain set and an advanced intercross population we demonstrate considerable improvements in significance and resolution for both loci. 1-LOD support intervals were improved 51% for Hipp1a and 37% for Hipp9a. We first generate locus-wise permuted P-values for association with the phenotype from multiple maps, which can be done using a permutation method appropriate to each population. These results are then assigned to defined physical positions by interpolation between markers with known physical and genetic positions. We then use Fisher's combination test to combine position-by-position probabilities among experiments. Finally, we calculate genome-wide combined P-values by generating locus-specific P-values for each permuted map for each experiment. These permuted maps are then sampled with replacement and combined. The distribution of best locus-specific P-values for each combined map is the null distribution of genome-wide adjusted P-values. CONCLUSIONS/SIGNIFICANCE: Our approach is applicable to a wide variety of segregating and non-segregating mapping populations, facilitates rapid refinement of physical QTL position, is complementary to other QTL fine mapping methods, and provides an appropriate genome-wide criterion of significance for combined mapping results.

  6. Diesel combustion and emissions formation using multiple 2-D imaging diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Dec, J.E. [Sandia National Labs., Livermore, CA (United States)

    1997-12-31

    Understanding how emissions are formed during diesel combustion is central to developing new engines that can comply with increasingly stringent emission standards while maintaining or improving performance levels. Laser-based planar imaging diagnostics are uniquely capable of providing the temporally and spatially resolved information required for this understanding. Using an optically accessible research engine, a variety of two-dimensional (2-D) imaging diagnostics have been applied to investigators of direct-injection (DI) diesel combustion and emissions formation. These optical measurements have included the following laser-sheet imaging data: Mie scattering to determine liquid-phase fuel distributions, Rayleigh scattering for quantitative vapor-phase-fuel/air mixture images, laser induced incandescence (LII) for relative soot concentrations, simultaneous LII and Rayleigh scattering for relative soot particle-size distributions, planar laser-induced fluorescence (PLIF) to obtain early PAH (polyaromatic hydrocarbon) distributions, PLIF images of the OH radical that show the diffusion flame structure, and PLIF images of the NO radical showing the onset of NO{sub x} production. In addition, natural-emission chemiluminescence images were obtained to investigate autoignition. The experimental setup is described, and the image data showing the most relevant results are presented. Then the conceptual model of diesel combustion is summarized in a series of idealized schematics depicting the temporal and spatial evolution of a reacting diesel fuel jet during the time period investigated. Finally, recent PLIF images of the NO distribution are presented and shown to support the timing and location of NO formation hypothesized from the conceptual model.

  7. Combining Information from Multiple Sources for the Diagnosis of Autism Spectrum Disorders for Toddlers and Young Preschoolers from 12 to 47 Months of Age

    Science.gov (United States)

    Kim, So Hyun; Lord, Catherine

    2012-01-01

    Background: Purpose of this study was to systematically examine combined use of the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) for children under age 4 using newly developed and revised diagnostic algorithms. Methods: Single and combined use of the ADI-R and ADOS algorithms were compared to…

  8. Peripheral (Seventh Nerve Palsy and Multiple Sclerosis: A Diagnostic Dilemma - A Case Report

    Directory of Open Access Journals (Sweden)

    Christian Saleh

    2016-01-01

    Full Text Available During the last decades, only a few cases on the association between peripheral demyelinating diseases and multiple sclerosis (MS have been reported. We describe the case of a young man who was initially diagnosed with Bell's palsy, and only after performing a brain MRI was the diagnosis of MS made. We review the literature and discuss some pitfalls which may lead to missing the diagnosis of MS.

  9. Multiple mutations and mutation combinations in the sodium channel of permethrin resistant mosquitoes, Culex quinquefasciatus

    Science.gov (United States)

    Li, Ting; Zhang, Lee; Reid, William R.; Xu, Qiang; Dong, Ke; Liu, Nannan

    2012-10-01

    A previous study identified 3 nonsynonymous and 6 synonymous mutations in the entire mosquito sodium channel of Culex quinquefasciatus, the prevalence of which were strongly correlated with levels of resistance and increased dramatically following insecticide selection. However, it is unclear whether this is unique to this specific resistant population or is a common mechanism in field mosquito populations in response to insecticide pressure. The current study therefore further characterized these mutations and their combinations in other field and permethrin selected Culex mosquitoes, finding that the co-existence of all 9 mutations was indeed correlated with the high levels of permethrin resistance in mosquitoes. Comparison of mutation combinations revealed several common mutation combinations presented across different field and permethrin selected populations in response to high levels of insecticide resistance, demonstrating that the co-existence of multiple mutations is a common event in response to insecticide resistance across different Cx. quinquefasciatus mosquito populations.

  10. Antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns: diagnostic accuracy for primary biliary cirrhosis.

    Science.gov (United States)

    Granito, A; Muratori, P; Muratori, L; Pappas, G; Cassani, F; Worthington, J; Guidi, M; Ferri, S; DE Molo, C; Lenzi, M; Chapman, R W; Bianchi, F B

    2006-12-01

    Serum antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns are frequently detected by indirect immunofluorescence on HEp-2 cells in patients with primary biliary cirrhosis. To assess the accuracy of multiple nuclear dot and rim-like/membranous antinuclear antibodies for the diagnosis of primary biliary cirrhosis. Sera from 4371 consecutive patients referred to our laboratory were analysed under code for antinuclear antibodies testing by indirect immunofluorescence on HEp-2 cells. Review of the clinical records of the 4371 patients allowed identification of 101 patients with antimitochondrial antibody-positive primary biliary cirrhosis and 22 with antimitochondrial antibody-negative variant. Multiple nuclear dot and/or rim-like/membranous patterns were found in 59 (1.3%) of the 4371 patients: 31 antimitochondrial antibody-positive primary biliary cirrhosis, 17 antimitochondrial antibody-negative primary biliary cirrhosis and 11 non-primary biliary cirrhosis. The specificity for primary biliary cirrhosis of both the antinuclear antibodies pattern was 99%. Positive predictive value and likelihood ratio for a positive test were 86% (95% CI: 72.7-94) and 221 (95% CI: 91.7-544) for multiple nuclear dot, 79% (95% CI: 62.2-90.1) and 132 (95% CI: 56.8-312.7) for rim-like/membranous, respectively. Multiple nuclear dot and rim-like/membranous antinuclear antibodies are rare findings. Their positivity strongly suggests the diagnosis of primary biliary cirrhosis, irrespective of antimitochondrial antibody status. The high specificity for primary biliary cirrhosis makes them a useful diagnostic tool especially in antimitochondrial antibody-negative patients.

  11. Clinical application of a novel diagnostic scheme including pancreatic β‑cell dysfunction for traumatic multiple organ dysfunction syndrome.

    Science.gov (United States)

    Wang, Zhan-Ke; Chen, Rong-Jian; Wang, Shi-Liang; Li, Guang-Wei; Zhu, Zhong-Zhen; Huang, Qiang; Chen, Zi-Li; Chen, Fan-Chang; Deng, Lei; Lan, Xiao-Peng; Hu, Tian

    2017-10-26

    A novel diagnostic scheme that includes pancreatic β‑cell dysfunction analysis for the diagnosis of traumatic multiple organ dysfunction syndrome (MODS) was investigated to assist in the early diagnosis and detection of MODS. Early intervention and treatment of MODS has been associated with a reduced mortality rate. A total of 2,876 trauma patients (including patients post‑major surgery) were admitted to the intensive care unit of the authors' hospital between December 2010 and December 2015 and enrolled in the present study. There were 205 cases where the patient succumbed to their injuries. In addition to the conventional diagnostic scheme for traumatic MODS, indexes of pancreatic β‑cell dysfunction [fasting blood‑glucose (FBG), homeostatic model assessment‑β and (blood insulin concentration 30 min following glucose loading‑fasting insulin concentration)/(blood glucose concentration 30 min following glucose loading‑FBG concentration)] were included to establish an improved diagnostic scheme for traumatic MODS. The novel scheme was subsequently used in clinical practice alongside the conventional scheme and its effect was evaluated. The novel scheme had a significantly higher positive number of MODS diagnoses for all trauma patients compared with the conventional scheme (12.48 vs. 8.87%; Pscheme (86.34%). The novel scheme had a significantly higher positive number of MODS diagnoses for trauma‑associated mortality patients 3 days prior to patients succumbing to MODS compared with the conventional scheme (80.98 vs. 64.39%; Pscheme and the conventional scheme was 100%; however, out of the patients diagnosed as positive by novel scheme 71.03% were positive by the conventional scheme. The consensus between the final MODS diagnosis and the MODS diagnosis 3 days prior to patients succumbing to their injuries between the novel scheme and the conventional scheme was 100%; however, out of the patients diagnosed as positive by novel scheme 97.79 were

  12. Next-generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes.

    Science.gov (United States)

    Mucci, Juan; Carmona, Santiago J; Volcovich, Romina; Altcheh, Jaime; Bracamonte, Estefanía; Marco, Jorge D; Nielsen, Morten; Buscaglia, Carlos A; Agüero, Fernán

    2017-10-01

    Chagas Disease, caused by the protozoan Trypanosoma cruzi, is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available. Accurate diagnosis is essential for the early identification and follow up of vector-borne cases and to prevent transmission of the disease by way of blood transfusions and organ transplantation. Diagnosis is routinely performed using serological methods, some of which require the production of parasite lysates, parasite antigenic fractions or purified recombinant antigens. Although available serological tests give satisfactory results, the production of reliable reagents remains laborious and expensive. Short peptides spanning linear B-cell epitopes have proven ideal serodiagnostic reagents in a wide range of diseases. Recently, we have conducted a large-scale screening of T. cruzi linear B-cell epitopes using high-density peptide chips, leading to the identification of several hundred novel sequence signatures associated to chronic Chagas Disease. Here, we performed a serological assessment of 27 selected epitopes and of their use in a novel multipeptide-based diagnostic method. A combination of 7 of these peptides were finally evaluated in ELISA format against a panel of 199 sera samples (Chagas-positive and negative, including sera from Leishmaniasis-positive subjects). The multipeptide formulation displayed a high diagnostic performance, with a sensitivity of 96.3% and a specificity of 99.15%. Therefore, the use of synthetic peptides as diagnostic tools are an attractive alternative in Chagas' disease diagnosis.

  13. Combination of DKK1 and AFP improves diagnostic accuracy of hepatocellular carcinoma compared with either marker alone.

    Science.gov (United States)

    Erdal, Harun; Gül Utku, Özlem; Karatay, Eylem; Çelik, Bülent; Elbeg, Şehri; Doğan, İbrahim

    2016-07-01

    The Wnt/ß-catenin pathway plays a prominent role in hepatocellular carcinoma (HCC). The Dickkopf (DKK) proteins (DKK1-4) are known Wnt antagonists; the overexpression of DKK1 has been demonstrated in HCC, and increased DKK3 methylation in the HCC tissue is associated with worse prognosis. Thus, the aim of our study was to demonstrate the diagnostic accuracy of serum DKK1 and DKK3 in HCC in comparison with that of serum alpha-fetoprotein (AFP). We included consecutive 40 HCC patients, 54 cirrhosis patients, and 39 healthy controls. Serum DKK1 and DKK3 levels were measured by an enzyme-linked immunosorbent assay, and serum AFP levels were measured by a chemiluminescence assay. The AFP levels differed in each group and could help differentiate between groups (p AFP increased the diagnostic yield, with a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 92.3%, 92.1%, and 87.8%, respectively. Although AFP is superior to DKK1 and DKK3 in the diagnosis of HCC, the combination of DKK1 and AFP showed a better diagnostic yield than AFP alone.

  14. Multiple linear combination (MLC) regression tests for common variants adapted to linkage disequilibrium structure.

    Science.gov (United States)

    Yoo, Yun Joo; Sun, Lei; Poirier, Julia G; Paterson, Andrew D; Bull, Shelley B

    2017-02-01

    By jointly analyzing multiple variants within a gene, instead of one at a time, gene-based multiple regression can improve power, robustness, and interpretation in genetic association analysis. We investigate multiple linear combination (MLC) test statistics for analysis of common variants under realistic trait models with linkage disequilibrium (LD) based on HapMap Asian haplotypes. MLC is a directional test that exploits LD structure in a gene to construct clusters of closely correlated variants recoded such that the majority of pairwise correlations are positive. It combines variant effects within the same cluster linearly, and aggregates cluster-specific effects in a quadratic sum of squares and cross-products, producing a test statistic with reduced degrees of freedom (df) equal to the number of clusters. By simulation studies of 1000 genes from across the genome, we demonstrate that MLC is a well-powered and robust choice among existing methods across a broad range of gene structures. Compared to minimum P-value, variance-component, and principal-component methods, the mean power of MLC is never much lower than that of other methods, and can be higher, particularly with multiple causal variants. Moreover, the variation in gene-specific MLC test size and power across 1000 genes is less than that of other methods, suggesting it is a complementary approach for discovery in genome-wide analysis. The cluster construction of the MLC test statistics helps reveal within-gene LD structure, allowing interpretation of clustered variants as haplotypic effects, while multiple regression helps to distinguish direct and indirect associations. © 2016 The Authors Genetic Epidemiology Published by Wiley Periodicals, Inc.

  15. Modern approaches to diagnostics of combined degenerative hip and spine pathology

    Directory of Open Access Journals (Sweden)

    V. V. Khominets

    2014-01-01

    Full Text Available The results of standard radiographs of 90 patients with hip-spine syndrome associated with one unilateral or bilateral III stage hip osteoarthhrosis were analyzed with the aim to improve the diagnostics of pathological changes in the "hip joint-pelvis- spine" complex. 12 parameters of sagittal spinal-pelvic balance and 3 parameters of frontal one were studied and the degenerative changes in spinal motional segments were evaluated. The statistical processing of obtained data was made. It was stated that the most frequent variant of sagittal spinal-pelvic profile is hyperlordosic one, followed by formation of degenerative changes especially in dorsal regions of spine (р=0,076.The strategy of patient examination with hip-spine syndrome was established from clinical and radiographic positions.

  16. Modelling multiple thresholds in meta-analysis of diagnostic test accuracy studies

    Directory of Open Access Journals (Sweden)

    Susanne Steinhauser

    2016-08-01

    Full Text Available Abstract Background In meta-analyses of diagnostic test accuracy, routinely only one pair of sensitivity and specificity per study is used. However, for tests based on a biomarker or a questionnaire often more than one threshold and the corresponding values of true positives, true negatives, false positives and false negatives are known. Methods We present a new meta-analysis approach using this additional information. It is based on the idea of estimating the distribution functions of the underlying biomarker or questionnaire within the non-diseased and diseased individuals. Assuming a normal or logistic distribution, we estimate the distribution parameters in both groups applying a linear mixed effects model to the transformed data. The model accounts for across-study heterogeneity and dependence of sensitivity and specificity. In addition, a simulation study is presented. Results We obtain a summary receiver operating characteristic (SROC curve as well as the pooled sensitivity and specificity at every specific threshold. Furthermore, the determination of an optimal threshold across studies is possible through maximization of the Youden index. We demonstrate our approach using two meta-analyses of B type natriuretic peptide in heart failure and procalcitonin as a marker for sepsis. Conclusions Our approach uses all the available information and results in an estimation not only of the performance of the biomarker but also of the threshold at which the optimal performance can be expected.

  17. A diagnostic algorithm combining clinical and molecular data distinguishes Kawasaki disease from other febrile illnesses

    Directory of Open Access Journals (Sweden)

    Ling Xuefeng B

    2011-12-01

    Full Text Available Abstract Background Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment. Methods Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls. Results Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919 in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969. The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803 effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease. Conclusions A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.

  18. Multiple Large Tumefactive MS Plaques in a Young Man: A Diagnostic Enigma and Therapeutic Challenge

    Directory of Open Access Journals (Sweden)

    Hossein Kalanie

    2012-01-01

    Full Text Available Tumefactive demyelinating lesion is defined as large solitary demyelinating lesion with imaging characteristics mimicking neoplasm. These atypical features include size more than 2 cm, mass effect, edema, and/or ring enhancement. Distinguishing tumefactive lesions from other etiologies of intracranial space occupying lesions is essential to avoid inadvertent surgical or toxic chemotherapeutic intervention. Symptoms are generally atypical for multiple sclerosis (MS and usually related to the pressure of a focal mass lesion without a history of MS. The clinical presentation and MRI appearance of these lesions often lead to biopsy. Here, we present a young man with fulminating neurological symptoms and multiple large tumefactive lesions on either hemisphere. Since patient and parents were not agreed on brain biopsy, a course of steroid therapy was commenced which ended to considerable improvement and confirmed the diagnosis of tumefactive MS. Thirteen months later, he experienced another relapse when his treatment was continued by weekly intramuscular injection of interferon b1a (Avonex. Two further MRIs showed shrinkage of tumefactive plaques and resolution of edema in the periphery of lesions.

  19. Case of multiple sulfatase deficiency and ocular albinism: a diagnostic odyssey.

    Science.gov (United States)

    Prasad, Chitra; Rupar, C Anthony; Campbell, Craig; Napier, Melanie; Ramsay, David; Tay, K Y; Sharan, Sapna; Prasad, Asuri N

    2014-09-01

    Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of lysosomal metabolism. The clinical phenotypic spectrum encompasses overlapping features of variable severity and is suggestive of individual single sulfatase deficiencies (i.e., metachromatic leukodystrophy, mucopolysaccharidosis, and X-linked ichthyosis). We describe a 3-year-old male with severe hypotonia, developmental regression and progressive neurodegeneration, coarse facial features, nystagmus (from ocular albinism), and dysmyelinating motor sensory neuropathy. Ethics approval was obtained from the Western University Ontario. Extensive investigative work-up identified deficiencies of multiple sulfatases: heparan sulfate sulfamidase: 6.5 nmoles/mg/protein/17 hour (reference 25.0-75.0), iduronate-2-sulfate sulfatase: 9 nmol/mg/protein/4 hour (reference 31-110), and arylsulfatase A: 3.8 nmoles/hr/mg protein (reference 22-50). The identification of compound heterozygous pathogenic mutations in the SUMF1 gene c.836 C>T (p.A279V) and c.1045C>T (p.R349W) confirmed the diagnosis of MSD. The complex clinical manifestations of MSD and the unrelated coexistence of ocular albinism as in our case can delay diagnosis. Genetic counselling should be provided to all affected families.

  20. Development of diagnostic model of lung cancer based on multiple tumor markers and data mining.

    Science.gov (United States)

    Wang, Zhaoxian; Feng, Feifei; Zhou, Xiaoshan; Duan, Liju; Wang, Jing; Wu, Yongjun; Wang, Na

    2017-11-07

    To develop early intelligent discriminative model of lung cancer and evaluate the efficiency of diagnosis value. Based on the genetic polymorphism profile of CYP1A1-rs1048943, GSTM1, mEH-rs1051740, XRCC1-rs1799782 and XRCC1-rs25489 and the methylations of p16 and RASSF1A gene, and the length of telomere in the peripheral blood from 200 lung cancer patients and 200 health persons, the discriminative model was established through decision tree and ANN technique. ACU of the discriminative model based on multiple tumour markers increased by about 10%; The accuracy rate of decision tree model and ANN model for testing set were 93.00% and 89.62% respectively. The ROC analysis showed the decision tree model's AUC is 0.929 (0.894∼0.964), the ANN model's AUC is 0.894 (0.853∼0.935). However, the classify accuracy rate and AUC of Fisher discriminatory analysis model are all about 0.7. The early intelligent discriminative model of lung cancer based on multiple tumor markers and data mining techniques has a higher accuracy rate and might be useful for early diagnosis of lung cancer.

  1. A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo.

    Directory of Open Access Journals (Sweden)

    Joyoti Dey

    Full Text Available While advances in high-throughput screening have resulted in increased ability to identify synergistic anti-cancer drug combinations, validation of drug synergy in the in vivo setting and prioritization of combinations for clinical development remain low-throughput and resource intensive. Furthermore, there is currently no viable method for prospectively assessing drug synergy directly in human patients in order to potentially tailor therapies. To address these issues we have employed the previously described CIVO platform and developed a quantitative approach for investigating multiple combination hypotheses simultaneously in single living tumors. This platform provides a rapid, quantitative and cost effective approach to compare and prioritize drug combinations based on evidence of synergistic tumor cell killing in the live tumor context. Using a gemcitabine resistant model of pancreatic cancer, we efficiently investigated nine rationally selected Abraxane-based combinations employing only 19 xenografted mice. Among the drugs tested, the BCL2/BCLxL inhibitor ABT-263 was identified as the one agent that synergized with Abraxane® to enhance acute induction of localized apoptosis in this model of human pancreatic cancer. Importantly, results obtained with CIVO accurately predicted the outcome of systemic dosing studies in the same model where superior tumor regression induced by the Abraxane/ABT-263 combination was observed compared to that induced by either single agent. This supports expanded use of CIVO as an in vivo platform for expedited in vivo drug combination validation and sets the stage for performing toxicity-sparing drug combination studies directly in cancer patients with solid malignancies.

  2. Parallel point-multiplication architecture using combined group operations for high-speed cryptographic applications.

    Science.gov (United States)

    Hossain, Md Selim; Saeedi, Ehsan; Kong, Yinan

    2017-01-01

    In this paper, we propose a novel parallel architecture for fast hardware implementation of elliptic curve point multiplication (ECPM), which is the key operation of an elliptic curve cryptography processor. The point multiplication over binary fields is synthesized on both FPGA and ASIC technology by designing fast elliptic curve group operations in Jacobian projective coordinates. A novel combined point doubling and point addition (PDPA) architecture is proposed for group operations to achieve high speed and low hardware requirements for ECPM. It has been implemented over the binary field which is recommended by the National Institute of Standards and Technology (NIST). The proposed ECPM supports two Koblitz and random curves for the key sizes 233 and 163 bits. For group operations, a finite-field arithmetic operation, e.g. multiplication, is designed on a polynomial basis. The delay of a 233-bit point multiplication is only 3.05 and 3.56 μs, in a Xilinx Virtex-7 FPGA, for Koblitz and random curves, respectively, and 0.81 μs in an ASIC 65-nm technology, which are the fastest hardware implementation results reported in the literature to date. In addition, a 163-bit point multiplication is also implemented in FPGA and ASIC for fair comparison which takes around 0.33 and 0.46 μs, respectively. The area-time product of the proposed point multiplication is very low compared to similar designs. The performance ([Formula: see text]) and Area × Time × Energy (ATE) product of the proposed design are far better than the most significant studies found in the literature.

  3. Combined intra-articular glucocorticoid, bupivacaine and morphine reduces pain and convalescence after diagnostic knee arthroscopy

    DEFF Research Database (Denmark)

    Rasmussen, Sten; Lorentzen, Jan S; Larsen, Allan S

    2002-01-01

    the procedure. Pain during movement and walking, leg muscle force and joint effusion, use of crutches and duration of sick leave were assessed. A combination of bupivacaine and morphine reduced pain, duration of immobilization and of convalescence. The addition of methylprednisolone further reduced pain, use...

  4. Diagnostic criteria in relation to the pathogenesis of familial combined hyperlipidemia.

    NARCIS (Netherlands)

    Graaf, J. de; Vleuten, G.M. van der; Stalenhoef, A.F.H.

    2004-01-01

    Familial combined hyperlipidemia (FCH) is the most common inherited hyperlipidemia in humans, affecting 1 to 3% of the adult population and up to 20% of patients with premature myocardial infarction. FCH is traditionally diagnosed by total plasma cholesterol and/or triglyceride levels above the 90th

  5. Combined influence of multiple climatic factors on the incidence of bacterial foodborne diseases.

    Science.gov (United States)

    Park, Myoung Su; Park, Ki Hwan; Bahk, Gyung Jin

    2018-01-01

    Information regarding the relationship between the incidence of foodborne diseases (FBD) and climatic factors is useful in designing preventive strategies for FBD based on anticipated future climate change. To better predict the effect of climate change on foodborne pathogens, the present study investigated the combined influence of multiple climatic factors on bacterial FBD incidence in South Korea. During 2011-2015, the relationships between 8 climatic factors and the incidences of 13 bacterial FBD, were determined based on inpatient stays, on a monthly basis using the Pearson correlation analyses, multicollinearity tests, principal component analysis (PCA), and the seasonal autoregressive integrated moving average (SARIMA) modeling. Of the 8 climatic variables, the combination of temperature, relative humidity, precipitation, insolation, and cloudiness was significantly associated with salmonellosis (Psnowfall, wind speed, duration of sunshine, and cloudiness were not significant for these 3 FBD. Other FBD, including campylobacteriosis, were not significantly associated with any combination of climatic factors. These findings indicate that the relationships between multiple climatic factors and bacterial FBD incidence can be valuable for the development of prediction models for future patterns of diseases in response to changes in climate. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Infectious and Noninfectious Granulomatosis in Patient with Multiple Sclerosis: Diagnostic Dilemmas and Followup

    Directory of Open Access Journals (Sweden)

    Jelena Paovic

    2014-01-01

    Full Text Available Patient was followed up over the course of 30 years. In 1978, after severe systemic infection followed by fever, pulmonary edema, and numerous neurological manifestations, patient was differentially diagnosed with apoplectic form of multiple sclerosis (MS, which was confirmed a year later via neurological and MRI findings. Approximately 20 years following the initial attack, sarcoidosis was diagnosed during the regular preoperative procedures required for cataract surgery. As consequence of lower immune system, infectious granulomatosis in form of pulmonary tuberculosis developed. Ophthalmological findings revealed bilateral retrobulbar neuritis (RBN approximately six years after initial attack. This developed into total uveitis with retinal periphlebitis and anterior granulomatous uveitis—all of which are clinically similar in both MS and sarcoidosis.

  7. Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles.

    Science.gov (United States)

    Hall, Judith G

    2014-08-01

    Arthrogryposis has been the term used to describe multiple congenital contractures for over a century. It is a descriptive term and present in over 400 specific conditions. Responsible gene abnormalities have been found for more than 150 specific types of arthrogryposis. Decreased fetal movement is present in all affected individuals which leads to a variety of secondary deformations. Decreased fetal movement (fetal akinesia) is associated with increased connective tissue around the immobilized joint, skin dimpling overlying the immobilized joint, disuse atrophy of the muscles that mobilize the joint and abnormal surface of the joint depending on the immobilized position. Other frequently observed features include: micrognathia, mildly shortened limbs, intrauterine growth restriction, pulmonary hypoplasia and short and/or immature gut. Primary etiologies include neuropathic processes; myopathic processes; end-plate abnormalities; maternal illness, trauma and drugs; limitation of fetal space; vascular compromise; and metabolic disorders to the developing embryo/fetus. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Comparing diagnostic accuracy of bedside ultrasound and radiography for bone fracture screening in multiple trauma patients at the ED.

    Science.gov (United States)

    Bolandparvaz, Shahram; Moharamzadeh, Payman; Jamali, Kazem; Pouraghaei, Mahboob; Fadaie, Maryam; Sefidbakht, Sepideh; Shahsavari, Kavous

    2013-11-01

    Long bone fractures are currently diagnosed using radiography, but radiography has some disadvantages (radiation and being time consuming). The present study compared the diagnostic accuracy of bedside ultrasound and radiography in multiple trauma patients at the emergency department (ED). The study assessed 80 injured patients with multiple trauma from February 2011 to July 2012. The patients were older than 18 years and triaged to the cardiopulmonary resuscitation ward of the ED. Bedside ultrasound and radiography were conducted for them. The findings were separately and blindly assessed by 2 radiologists. Sensitivity, specificity, the positive and negative predictive value, and κ coefficient were measured to assess the accuracy and validity of ultrasound as compared with radiography. The sensitivity of ultrasound for diagnosis of limb bone fractures was not high enough and ranged between 55% and 75% depending on the fracture site. The specificity of this diagnostic method had an acceptable range of 62% to 84%. Ultrasound negative prediction value was higher than other indices under study and ranged between 73% and 83%, but its positive prediction value varied between 33.3% and 71%. The κ coefficient for diagnosis of long bone fractures of upper limb (κ = 0.58) and upper limb joints (κ = 0.47) and long bones of lower limb (κ = 0.52) was within the medium range. However, the value for diagnosing fractures of lower limb joints (κ = 0.47) was relatively low. Bedside ultrasound is not a reliable method for diagnosing fractures of upper and lower limb bones compared with radiography. © 2013 Elsevier Inc. All rights reserved.

  9. Luminex xMAP combined with Western blot improves HIV diagnostic sensitivity.

    Science.gov (United States)

    Kong, Weiwei; Li, Yan; Cheng, Shaohui; Yan, Chen; An, Shiping; Dong, Zheng; Yan, Lina; Yuan, Yuhua

    2016-01-01

    Currently, Western blot is used to confirm the initial serodiagnosis of HIV infection by antibody detection. However, a major deficiency of the Western blot relates to a lack of sufficient sensitivity in detecting HIV antibodies. This report describes a simple, sensitive and inexpensive bead-based assay for detection of early HIV infection. A panel of 138 positive specimens including 105 blood donors and 33 MSM with known Western blot results were evaluated using Luminex xMAP at Tianjin Centers for Disease Control and Prevention (CDC). We demonstrate a superior sensitivity of Luminex xMAP compared with Western blot. Of the 87 confirmed HIV positive blood donors, Western blot only confirmed 65 cases with 74.7% (65/87) sensitivity while Luminex xMAP identified 72 cases with 82.8% (72/87) sensitivity (pWestern blot and Luminex xMAP verified 13 and 19 of 33 MSM specimens, respectively. The sensitivity was 39.4% (13/33) for Western blot and 57.6% (19/33) for Luminex xMAP (pWestern blot improves the diagnostic sensitivity of HIV infection at an early stage, and reduces the chances of missed diagnosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Combination therapy of Avonex and doxycycline in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Naser Sharafaddinzadeh

    2011-01-01

    Full Text Available Background: Multiple sclerosis is an inflammatory, chronic demyelinating disease of the central nervous system (CNS with unknown etiology. Multiple sclerosis causes disability in young people. An Immunomodulatory drug like Avonex (IFN β1a is used to prevent relapses or disease progression. The aim of this study is to evaluate efficacy of combination therapy (Avonex and doxycycline with standard therapy (Avonex in remitting-relapsing multiple sclerosis (RRMS.Materials and Method: A double blind clinical trial was conducted. During four-month study period, 46 patients with RRMS, under standard medication (Avonex, were entered into the study. Their EDSS score were between 1-5. They randomly allocated in to two study groups with 23cases in each arm (cases and controls. All cases were allocated to each group based on blocking method. They received Avonex only in control group and Avonex and doxycycline in case group. EDSS was measured in both groups in the beginning and at the end of study. First EDSS and EDSS scores at the end of first, second, third and fourth months in both groups were compared. Number and rate of clinical attacks and side effects of treatment were assessed in both groups. Results: In case group, there was significant changes between the first EDSS and final EDSS score, but there was not any statistically significant finding in control group after 4 months. There was no significant difference between case and control group in EDSS scores during four-month study period and there was not significant difference between case and control groups in clinical attacks. Combination therapy was well tolerated without additive side effects. Conclusion: It seems that combination of both Avonex and doxycycline in RRMS patients were effective, safe, and well tolerated

  11. Combining polarimetry and spectropolarimetry techniques in diagnostics of cancer changes in biological tissues

    Science.gov (United States)

    Yermolenko, Sergey; Ivashko, Pavlo; Gruia, Ion; Gruia, Maria; Peresunko, Olexander; Zelinska, Natalia; Voloshynskyi, Dmytro; Fedoruk, Olexander; Zimnyakov, Dmitry; Alonova, Marina

    2015-02-01

    The aim of the study is combining polarimetry and spectropolarimetry techniques for identifying the changes of opticalgeometrical structure in different kinds of biotissues with solid tumours. It is researched that a linear dichroism appears in biotissues (human esophagus, muscle tissue of rats, human prostate tissue, cervical smear) with cancer diseases, magnitude of which depends on the type of the tissue and on the time of cancer process development.

  12. Research on the reliability of friction system under combined additive and multiplicative random excitations

    Science.gov (United States)

    Sun, Jiaojiao; Xu, Wei; Lin, Zifei

    2018-01-01

    In this paper, the reliability of a non-linearly damped friction oscillator under combined additive and multiplicative Gaussian white noise excitations is investigated. The stochastic averaging method, which is usually applied to the research of smooth system, has been extended to the study of the reliability of non-smooth friction system. The results indicate that the reliability of friction system can be improved by Coulomb friction and reduced by random excitations. In particular, the effect of the external random excitation on the reliability is larger than the effect of the parametric random excitation. The validity of the analytical results is verified by the numerical results.

  13. [Multiple and combined injuries to chest and abdomen as an unresolved surgical problem].

    Science.gov (United States)

    Abakumov, M M

    2010-01-01

    Peculiar features of surgical treatment of gunshot, non-lethal arm, and cold steel wounds are formulated based on the 20-year experience with managing 20,000 injured subjects having multiple and combined injuries to neck, chest, and abdomen of suicidal and criminal character. The growth in the number of patients with suicidal wounds and hemocontact viral infections (hepatitis, HIV) is emphasized. It is concluded that assessment of the state of gas exchange, lipid peroxidation, antioxidative, and immune systems does not give full idea of pathogenetic mechanisms of traumatic diseases.

  14. A Reconfiguration Control Scheme for a Quadrotor Helicopter via Combined Multiple Models

    Directory of Open Access Journals (Sweden)

    Fuyang Chen

    2014-08-01

    Full Text Available In this paper, an optimal reconfiguration control scheme is proposed for a quadrotor helicopter with actuator faults via adaptive control and combined multiple models. The combined models set contains several fixed models, an adaptive model and a reinitialized adaptive model. The fixed models and the adaptive model can describe the failure system under different fault conditions. Moreover, the proposed reinitialized adaptive model refers to the closest model of the current system and can improve the speed of convergence effectively. In addition, the reference model is designed in consideration of an optimal control performance index and the principle of the minimum cost to achieve perfect tracking performance. Finally, some simulation results demonstrate the effectiveness of the proposed reconfiguration control scheme for faulty cases.

  15. Multiple and high-throughput droplet reactions via combination of microsampling technique and microfluidic chip

    KAUST Repository

    Wu, Jinbo

    2012-11-20

    Microdroplets offer unique compartments for accommodating a large number of chemical and biological reactions in tiny volume with precise control. A major concern in droplet-based microfluidics is the difficulty to address droplets individually and achieve high throughput at the same time. Here, we have combined an improved cartridge sampling technique with a microfluidic chip to perform droplet screenings and aggressive reaction with minimal (nanoliter-scale) reagent consumption. The droplet composition, distance, volume (nanoliter to subnanoliter scale), number, and sequence could be precisely and digitally programmed through the improved sampling technique, while sample evaporation and cross-contamination are effectively eliminated. Our combined device provides a simple model to utilize multiple droplets for various reactions with low reagent consumption and high throughput. © 2012 American Chemical Society.

  16. Combining multiple features for error detection and its application in brain-computer interface.

    Science.gov (United States)

    Tong, Jijun; Lin, Qinguang; Xiao, Ran; Ding, Lei

    2016-02-04

    Brain-computer interface (BCI) is an assistive technology that conveys users' intentions by decoding various brain activities and translating them into control commands, without the need of verbal instructions and/or physical interactions. However, errors existing in BCI systems affect their performance greatly, which in turn confines the development and application of BCI technology. It has been demonstrated viable to extract error potential from electroencephalography recordings. This study proposed a new approach of fusing multiple-channel features from temporal, spectral, and spatial domains through two times of dimensionality reduction based on neural network. 26 participants (13 males, mean age = 28.8 ± 5.4, range 20-37) took part in the study, who engaged in a P300 speller task spelling cued words from a 36-character matrix. In order to evaluate the generalization ability across subjects, the data from 16 participants were used for training and the rest for testing. The total classification accuracy with combination of features is 76.7 %. The receiver operating characteristic (ROC) curve and area under ROC curve (AUC) further indicate the superior performance of the combination of features over any single features in error detection. The average AUC reaches 0.7818 with combined features, while 0.7270, 0.6376, 0.7330 with single temporal, spectral, and spatial features respectively. The proposed method combining multiple-channel features from temporal, spectral, and spatial domain has better classification performance than any individual feature alone. It has good generalization ability across subject and provides a way of improving error detection, which could serve as promising feedbacks to promote the performance of BCI systems.

  17. Diagnostic accuracy of combined coronary angiography and adenosine stress myocardial perfusion imaging using 320-detector computed tomography: pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Nasis, Arthur; Ko, Brian S.; Leung, Michael C.; Antonis, Paul R.; Wong, Dennis T.; Kyi, Leo; Cameron, James D.; Meredith, Ian T.; Seneviratne, Sujith K. [Southern Health and Monash University, Monash Cardiovascular Research Centre, Monash Heart, Department of Medicine Monash Medical Centre (MMC), Melbourne (Australia); Nandurkar, Dee; Troupis, John M. [MMC, Southern Health, Department of Diagnostic Imaging, Melbourne (Australia)

    2013-07-15

    To determine the diagnostic accuracy of combined 320-detector row computed tomography coronary angiography (CTA) and adenosine stress CT myocardial perfusion imaging (CTP) in detecting perfusion abnormalities caused by obstructive coronary artery disease (CAD). Twenty patients with suspected CAD who underwent initial investigation with single-photon-emission computed tomography myocardial perfusion imaging (SPECT-MPI) were recruited and underwent prospectively-gated 320-detector CTA/CTP and invasive angiography. Two blinded cardiologists evaluated invasive angiography images quantitatively (QCA). A blinded nuclear physician analysed SPECT-MPI images for fixed and reversible perfusion defects. Two blinded cardiologists assessed CTA/CTP studies qualitatively. Vessels/territories with both >50 % stenosis on QCA and corresponding perfusion defect on SPECT-MPI were defined as ischaemic and formed the reference standard. All patients completed the CTA/CTP protocol with diagnostic image quality. Of 60 vessels/territories, 17 (28 %) were ischaemic according to QCA/SPECT-MPI criteria. Sensitivity, specificity, PPV, NPV and area under the ROC curve for CTA/CTP was 94 %, 98 %, 94 %, 98 % and 0.96 (P < 0.001) on a per-vessel/territory basis. Mean CTA/CTP radiation dose was 9.2 {+-} 7.4 mSv compared with 13.2 {+-} 2.2 mSv for SPECT-MPI (P < 0.001). Combined 320-detector CTA/CTP is accurate in identifying obstructive CAD causing perfusion abnormalities compared with combined QCA/SPECT-MPI, achieved with lower radiation dose than SPECT-MPI. (orig.)

  18. Storm diagnostic/predictive images derived from a combination of lightning and satellite imagery

    Science.gov (United States)

    Goodman, Steven J.; Buechler, Dennis E.; Meyer, Paul J.

    1988-01-01

    A technique is presented for generating trend or convective tendency images using a combination of GOES satellite imagery and cloud-to-ground lightning observations. The convective tendency images can be used for short term forecasting of storm development. A conceptual model of cloud electrical development and an example of the methodology used to generate lightning/satellite convective tendency imagery are given. Successive convective tendency images can be looped or animated to show the previous growth or decay of thunderstorms and their associated lighting activity. It is suggested that the convective tendency image may also be used to indicate potential microburst producing storms.

  19. Identification and differentiation of Panax ginseng, Panax quinquefolium, and Panax notoginseng by monitoring multiple diagnostic chemical markers

    Directory of Open Access Journals (Sweden)

    Wenzhi Yang

    2016-10-01

    Full Text Available To differentiate traditional Chinese medicines (TCM derived from congeneric species in TCM compound preparations is usually challenging. The roots of Panax ginseng (PG, Panax quinquefolium (PQ and Panax notoginseng (PN are used as popular TCM. They contain similar triterpenoid saponins (ginsenosides as the major bioactive constituents. Thus far, only a few chemical markers have been discovered to differentiate these three species. Herein we present a multiple marker detection approach to effectively differentiate the three Panax species, and to identify them in compound preparations. Firstly, 85 batches of crude drug samples (including 32 PG, 30 PQ, and 23 PN were analyzed by monitoring 40 major ginsenosides in the extracted ion chromatograms (EICs using a validated LC–MS fingerprinting method. Secondly, the samples were clustered into different groups by pattern recognition chemometric approaches using PLS-DA and OPLS-DA models, and 17 diagnostic chemical markers were discovered. Aside from the previously known Rf and p-F11, ginsenoside Rs1 could be a new marker to differentiate PG from PQ. Finally, the above multiple chemical markers were used to identify the Panax species in 60 batches of TCM compound preparations.

  20. Diagnostic performance of combined single photon emission computed tomographic scintimammography and ultrasonography based on computer-aided diagnosis for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Kyung Hoon; Choi, Duck Joo; Choe, Won Sick [Gachon Universtiy Gil Medical Center, Incheon (Korea, Republic of); Lee, Jun Gu; Kim, Jong Hyo [Seoul National University, College of Medicine, Seoul (Korea, Republic of); Lee, Hyung Ji; Om, Kyong Sik [CAD Impact, Inc., Seoul (Korea, Republic of); Lee, Byeong Il [Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2007-06-15

    We investigated whether the diagnostic performance of SPECT scintimammography (SMM) can be improved by adding computer-aided diagnosis (CAD) of ultrasonography (US). We reviewed breast SPECT SMM images and corresponding US images from 40 patients with breast masses (21 malignant and 19 benign tumors.) The quantitative data of SPECT SMM were obtained as the uptake ratio of lesion to contralateral normal breast. The morphologic features of the breast lesions on US were extracted and quantitated using the automated CAD software program. The diagnostic performance of SPECT SMM and CAD of US alone was determined using receiver operating characteristic (ROC) curve analysis. The best discriminating parameter (D-value) combining SPECT SMM and the CAD of US was created. The sensitivity, specificity and accuracy of combined two diagnostic modalities were compared to those of a single one. Both SPECT SMM and CAD of US showed a relatively good diagnostic performance (area under curve=0.846 and 0.831, respectively). Combining the results of SPECT SMM and CAD of US resulted in improved diagnostic performance (area under curve=0.860), but there was no statistical difference in sensitivity, specificity and accuracy between the combined method and a single modality. It seems that combining the results of SPECT SMM and CAD of breast US do not significantly improve the diagnostic performance for diagnosis of breast cancer, compared with that of SPECT SMM alone. However, SPECT SMM and CAD of US may complement each other in differential diagnosis of breast cancer.

  1. Validation and calibration of structural models that combine information from multiple sources.

    Science.gov (United States)

    Dahabreh, Issa J; Wong, John B; Trikalinos, Thomas A

    2017-02-01

    Mathematical models that attempt to capture structural relationships between their components and combine information from multiple sources are increasingly used in medicine. Areas covered: We provide an overview of methods for model validation and calibration and survey studies comparing alternative approaches. Expert commentary: Model validation entails a confrontation of models with data, background knowledge, and other models, and can inform judgments about model credibility. Calibration involves selecting parameter values to improve the agreement of model outputs with data. When the goal of modeling is quantitative inference on the effects of interventions or forecasting, calibration can be viewed as estimation. This view clarifies issues related to parameter identifiability and facilitates formal model validation and the examination of consistency among different sources of information. In contrast, when the goal of modeling is the generation of qualitative insights about the modeled phenomenon, calibration is a rather informal process for selecting inputs that result in model behavior that roughly reproduces select aspects of the modeled phenomenon and cannot be equated to an estimation procedure. Current empirical research on validation and calibration methods consists primarily of methodological appraisals or case-studies of alternative techniques and cannot address the numerous complex and multifaceted methodological decisions that modelers must make. Further research is needed on different approaches for developing and validating complex models that combine evidence from multiple sources.

  2. Combination of Multiple Resistance Traits from Wild Relative Species in Chrysanthemum via Trigeneric Hybridization

    Science.gov (United States)

    Deng, Yanming; Jiang, Jiafu; Chen, Sumei; Teng, Nianjun; Song, Aiping; Guan, Zhiyong; Fang, Weimin; Chen, Fadi

    2012-01-01

    Background With the objective of combining multiple resistant traits from wild relative species in florist’s chrysanthemums, trigeneric hybridization was conducted by crossing two intergeneric F1 hybrids Chrysanthemum grandiflorum × Artemisia vulgaris and Chrysanthemum crassum × Crossostephium chinense. Methodology/Principal Findings To assess post-pollination phenomena, we investigated pollen germination on the stigma and embryo development, using fluorescence and scanning electron microscopy and paraffin-embedded sections, respectively. We selected eight putative trigeneric hybrid lines that showed the greatest morphological differences from the parents from among the progeny derived via embryo rescue. The hybridity of one trigeneric hybrid was further confirmed by fluorescent genomic in situ hybridization; in addition, the aphid resistance and salt tolerance of this hybrid were higher than those of the chrysanthemum parent and the C. grandiflorum × A. vulgaris F1 hybrid, respectively. Conclusions/Significance The enhanced aphid resistance of the hybrid line reflects the inheritance of chromosomes from A. vulgaris, which carries genes that encode bioactive components. The enhanced salt tolerance of the trigeneric hybrid is attributable to inheritance of genetic materials from Chrysanthemum crassum and Crossostephium chinense, which act to maintain the compartmentation of Na+ and K+ ions and their selective transportation among different organs to avert deleterious effects and protect the photosynthetic apparatus. The results indicate that trigeneric hybridization between different bigeneric hybrids is a promising method for combination of multiple stress-resistance traits for improvement of chrysanthemum. PMID:22952958

  3. Combination total lymphoid irradiation and low-dose corticosteroid therapy for progressive multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cook, S.D.; Zito, G.; Dowling, P.C. [University of Medicine and Dentistry of New Jersey, Department of Neurosciences, Newark, and Neurology Service, Department of Veterans Affairs Medical Center, NJ (United States); Devereux, C. [Univrsity of Medicine and Dentistry of New Jersey, Department of Neurosciences, Newark, and Radiation Oncology, Clara Maass Medical Center, Belleville, NU (United States); Troiano, R.; Jotkowitz, A.; Rohowsky-Kochan, C. [University of Medicine and Dentistry of New Jersey, Department of Neurosciences, Newark (United States); Sheffet, A. [University of Medicine and Dentistry of New Jersey, Department of Preventive Medicine and Community Health, Newark (United States)

    1995-01-01

    Total lymphoid irradiation (TLI) has been reported to delay deterioration in patients with progressive multiple sclerosis and other autoimmune disorders. Methods - In an open trial, the effect of TLI combined with a one year course of low dose prednisone was compared to the effect of sham TLI and TLI only in a prior double-blind study of patients with progressive multiple sclerosis. Results - Twenty-seven patients receiving TLI combined with corticosteroids had significantly greater lymphocytopenia in the year post-therapy than those receiving TLI only or sham TLI and Kaplan Meier product-limit survival analysis showed significantly less progression in the TLI plus steroid group over 4 years of follow-up. No difference in lymphocytopenia or progression was found with TLI plus corticosteroid therapy when the spleen was removed from the field of irradiation. Conclusion - These results lend further support to the hypothesis that TLI may be effective in progressive MS, and indicates that adding low-dose prednisone may enhance this effect. The study also suggests that TLI may be equally effective whether or not the spleen is irradiated. (au) (14 refs.).

  4. Combination of multiple resistance traits from wild relative species in Chrysanthemum via trigeneric hybridization.

    Science.gov (United States)

    Deng, Yanming; Jiang, Jiafu; Chen, Sumei; Teng, Nianjun; Song, Aiping; Guan, Zhiyong; Fang, Weimin; Chen, Fadi

    2012-01-01

    With the objective of combining multiple resistant traits from wild relative species in florist's chrysanthemums, trigeneric hybridization was conducted by crossing two intergeneric F(1) hybrids Chrysanthemum grandiflorum × Artemisia vulgaris and Chrysanthemum crassum × Crossostephium chinense. To assess post-pollination phenomena, we investigated pollen germination on the stigma and embryo development, using fluorescence and scanning electron microscopy and paraffin-embedded sections, respectively. We selected eight putative trigeneric hybrid lines that showed the greatest morphological differences from the parents from among the progeny derived via embryo rescue. The hybridity of one trigeneric hybrid was further confirmed by fluorescent genomic in situ hybridization; in addition, the aphid resistance and salt tolerance of this hybrid were higher than those of the chrysanthemum parent and the C. grandiflorum × A. vulgaris F(1) hybrid, respectively. The enhanced aphid resistance of the hybrid line reflects the inheritance of chromosomes from A. vulgaris, which carries genes that encode bioactive components. The enhanced salt tolerance of the trigeneric hybrid is attributable to inheritance of genetic materials from Chrysanthemum crassum and Crossostephium chinense, which act to maintain the compartmentation of Na(+) and K(+) ions and their selective transportation among different organs to avert deleterious effects and protect the photosynthetic apparatus. The results indicate that trigeneric hybridization between different bigeneric hybrids is a promising method for combination of multiple stress-resistance traits for improvement of chrysanthemum.

  5. Treatment of multiple gingival recessions using a coronally advanced flap procedure combined with button application.

    Science.gov (United States)

    Ozcelik, Onur; Haytac, M Cenk; Seydaoglu, Gulsah

    2011-06-01

    The purpose of this randomized controlled clinical trial was to evaluate the effectiveness of a new treatment approach, which consists of coronally advanced flap (CAF) procedure combined with orthodontic button application (CAF+B) for the treatment of multiple recession-type defects in patients with aesthetic demands. Forty-one healthy subjects presenting at least three adjacent Miller Class I or II multiple gingival recessions were treated with a CAF technique. Twenty-one patients were randomly assigned to the test group, and the other 20 patients were assigned to the control group. On the test group, orthodontic buttons were used for the stabilization of advanced flaps. Clinical and patient centered parameters were measured at baseline, 7 days and 6 months after the surgery. A total of 155 recessions were treated. Complete root coverage from baseline to 6 months post-surgery was 61% for the control group and 84% for the test group. There was no difference on visual analog scale-pain measurements among the treatment groups. Patient satisfaction with aesthetics was very high in CAF+B group when compared with CAF group. Six months results showed that the CAF+B approach was effective for the treatment of multiple gingival recessions in patients with aesthetic demands. © 2011 John Wiley & Sons A/S.

  6. Nanomedicine: nanoparticles, molecular biosensors, and targeted gene/drug delivery for combined single-cell diagnostics and therapeutics

    Science.gov (United States)

    Prow, Tarl W.; Salazar, Jose H.; Rose, William A.; Smith, Jacob N.; Reece, Lisa; Fontenot, Andrea A.; Wang, Nan A.; Lloyd, R. Stephen; Leary, James F.

    2004-07-01

    Next generation nanomedicine technologies are being developed to provide for continuous and linked molecular diagnostics and therapeutics. Research is being performed to develop "sentinel nanoparticles" which will seek out diseased (e.g. cancerous) cells, enter those living cells, and either perform repairs or induce those cells to die through apoptosis. These nanoparticles are envisioned as multifunctional "smart drug delivery systems". The nanosystems are being developed as multilayered nanoparticles (nanocrystals, nanocapsules) containing cell targeting molecules, intracellular re-targeting molecules, molecular biosensor molecules, and drugs/enzymes/gene therapy. These "nanomedicine systems" are being constructed to be autonomous, much like present-day vaccines, but will have sophisticated targeting, sensing, and feedback control systems-much more sophisticated than conventional antibody-based therapies. The fundamental concept of nanomedicine is to not to just kill all aberrant cells by surgery, radiation therapy, or chemotherapy. Rather it is to fix cells, when appropriate, one cell-at-a-time, to preserve and re-build organ systems. When cells should not be fixed, such as in cases where an improperly repaired cell might give rise to cancer cells, the nanomedical therapy would be to induce apoptosis in those cells to eliminate them without the damagin bystander effects of the inflammatory immune response system reacting to necrotic cells or those which have died from trauma or injury. The ultimate aim of nanomedicine is to combine diagnostics and therapeutics into "real-time medicine", using where possible in-vivo cytometry techniques for diagnostics and therapeutics. A number of individual components of these multi-component nanoparticles are already working in in-vitro and ex-vivo cell and tissue systems. Work has begun on construction of integrated nanomedical systems.

  7. Next-generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes.

    Directory of Open Access Journals (Sweden)

    Juan Mucci

    2017-10-01

    Full Text Available Chagas Disease, caused by the protozoan Trypanosoma cruzi, is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available. Accurate diagnosis is essential for the early identification and follow up of vector-borne cases and to prevent transmission of the disease by way of blood transfusions and organ transplantation. Diagnosis is routinely performed using serological methods, some of which require the production of parasite lysates, parasite antigenic fractions or purified recombinant antigens. Although available serological tests give satisfactory results, the production of reliable reagents remains laborious and expensive. Short peptides spanning linear B-cell epitopes have proven ideal serodiagnostic reagents in a wide range of diseases. Recently, we have conducted a large-scale screening of T. cruzi linear B-cell epitopes using high-density peptide chips, leading to the identification of several hundred novel sequence signatures associated to chronic Chagas Disease. Here, we performed a serological assessment of 27 selected epitopes and of their use in a novel multipeptide-based diagnostic method. A combination of 7 of these peptides were finally evaluated in ELISA format against a panel of 199 sera samples (Chagas-positive and negative, including sera from Leishmaniasis-positive subjects. The multipeptide formulation displayed a high diagnostic performance, with a sensitivity of 96.3% and a specificity of 99.15%. Therefore, the use of synthetic peptides as diagnostic tools are an attractive alternative in Chagas' disease diagnosis.

  8. Next-generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes

    Science.gov (United States)

    Volcovich, Romina; Altcheh, Jaime; Bracamonte, Estefanía; Marco, Jorge D.; Nielsen, Morten; Buscaglia, Carlos A.

    2017-01-01

    Chagas Disease, caused by the protozoan Trypanosoma cruzi, is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available. Accurate diagnosis is essential for the early identification and follow up of vector-borne cases and to prevent transmission of the disease by way of blood transfusions and organ transplantation. Diagnosis is routinely performed using serological methods, some of which require the production of parasite lysates, parasite antigenic fractions or purified recombinant antigens. Although available serological tests give satisfactory results, the production of reliable reagents remains laborious and expensive. Short peptides spanning linear B-cell epitopes have proven ideal serodiagnostic reagents in a wide range of diseases. Recently, we have conducted a large-scale screening of T. cruzi linear B-cell epitopes using high-density peptide chips, leading to the identification of several hundred novel sequence signatures associated to chronic Chagas Disease. Here, we performed a serological assessment of 27 selected epitopes and of their use in a novel multipeptide-based diagnostic method. A combination of 7 of these peptides were finally evaluated in ELISA format against a panel of 199 sera samples (Chagas-positive and negative, including sera from Leishmaniasis-positive subjects). The multipeptide formulation displayed a high diagnostic performance, with a sensitivity of 96.3% and a specificity of 99.15%. Therefore, the use of synthetic peptides as diagnostic tools are an attractive alternative in Chagas’ disease diagnosis. PMID:28991925

  9. Combining ecosystem service relationships and DPSIR framework to manage multiple ecosystem services.

    Science.gov (United States)

    Xue, Hui; Li, Shiyu; Chang, Jie

    2015-03-01

    Ecosystem service (ES) relationship occurs due to two types of mechanisms: (1) interact directly or (2) interact through the impact of a shared factor. Identifying such mechanisms behind ES relationship within a single land-use/land-cover category and combining it with a system thinking framework is especially necessary for effective decision-making to manage multiple ESs generated by this land-use/land-cover. In this study, we use tea plantations in China to investigate mechanisms behind ES relationships. We find that tea production is positively correlated with four regulating services (i.e., carbon sequestration, soil N protection, soil P protection, and water conservation). Several regulating services, such as carbon sequestration and soil N, P, and K protection, have positive correlations with each other. Tea production, carbon sequestration, and soil retention are significantly correlated with local annual mean temperature and precipitation. We then establish driver-pressure-state-impact-response (DPSIR) framework for tea plantations, which has been widely used for environmental management issues. Integrating our findings of ES relationship into DPSIR framework, we can estimate how ES change is responding to two types of responses: response to control drivers and response to maintain or restore state. Scenario analysis showed that the responses to control drivers have a larger impact on ES. We discuss that DPSIR would favor managing multiple ES because it enables a more precise understanding of how ES interacts through the effects of factors from various hierarchies. Finally, we suggest integrating ES direct interaction into DPSIR framework. We think such integration could improve the ability of DPSIR framework to support decision-making in multiple ES management, specifically in at least three aspects: (1) favor to identify all possible response alternatives, (2) enable us to evaluate ES which cannot be assessed if without such combining, and (3) help to

  10. Laser microtreatment for genetic manipulations and DNA diagnostics by a combination of microbeam and photonic tweezers (laser microbeam trap)

    Science.gov (United States)

    Greulich, Karl-Otto; Monajembashi, Shamci; Celeda, D.; Endlich, N.; Eickhoff, Holger; Hoyer, Carsten; Leitz, G.; Weber, Gerd; Scheef, J.; Rueterjans, H.

    1994-12-01

    Genomes of higher organisms are larger than one typically expects. For example, the DNA of a single human cell is almost two meters long, the DNA in the human body covers the distance Earth-Sun approximately 140 times. This is often not considered in typical molecular biological approaches for DNA diagnostics, where usually only DNA of the length of a gene is investigated. Also, one basic aspect of sequencing the human genome is not really solved: the problem how to prepare the huge amounts of DNA required. Approaches from biomedical optics combined with new developments in single molecule biotechnology may at least contribute some parts of the puzzle. A large genome can be partitioned into portions comprising approximately 1% of the whole DNA using a laser microbeam. The single DNA fragment can be amplified by the polymerase chain reaction in order to obtain a sufficient amount of molecules for conventional DNA diagnostics or for analysis by octanucleotide hybridization. When not amplified by biotechnological processes, the individual DNA molecule can be visualized in the light microscope and can be manipulated and dissected with the laser microbeam trap. The DNA probes obtained by single molecule biotechnology can be employed for fluorescence in situ introduced into plant cells and subcellular structures even when other techniques fail. Since the laser microbeam trap allows to work in the interior of a cell without opening it, subcellular structures can be manipulated. For example, in algae, such structures can be moved out of their original position and used to study intracellular viscosities.

  11. Diagnostic accuracy of semiautomatic lesion detection plus quantitative susceptibility mapping in the identification of new and enhancing multiple sclerosis lesions.

    Science.gov (United States)

    Zhang, Shun; Nguyen, Thanh D; Zhao, Yize; Gauthier, Susan A; Wang, Yi; Gupta, Ajay

    2018-01-01

    To evaluate the diagnostic accuracy of a novel non-contrast brain MRI method based on semiautomatic lesion detection using T2w FLAIR subtraction image, the statistical detection of change (SDC) algorithm (T2w + SDC), and quantitative susceptibility mapping (QSM). This method identifies new lesions and discriminates between enhancing and nonenhancing lesions in multiple sclerosis (MS). Thirty three MS patients who had MRIs at two different time points with at least one new Gd-enhancing lesion on the 2nd MRI were included in the study. For a reference standard, new lesions were identified by two neuroradiologists on T2w and post-Gd T1w images with the help of T2w + SDC. The diagnostic accuracy of the proposed method based on QSM and T2w + SDC lesion detection (T2w + SDC + QSM) for assessing lesion enhancement status was determined. Receiver operating characteristic (ROC) analysis was performed to compute the optimal lesion susceptibility cutoff value. A total of 165 new lesions (54 enhancing, 111 nonenhancing) were identified. The sensitivity and specificity of T2w + SDC + QSM in predicting lesion enhancement status were 90.7% and 85.6%, respectively. For lesions ≥50 mm 3 , ROC analysis showed an optimal QSM cutoff value of 13.5 ppb with a sensitivity of 88.4% and specificity of 88.6% (0.93, 95% CI, 0.87-0.99). For lesions ≥15 mm 3 , the optimal QSM cutoff was 15.4 ppb with a sensitivity of 77.9% and specificity of 94.0% (0.93, 95% CI, 0.89-0.97). The proposed T2w + SDC + QSM method is highly accurate for identifying and predicting the enhancement status of new MS lesions without the use of Gd injection.

  12. Investigation of strategies for drug delivery by combination targeting of nanocarriers to multiple epitopes or receptors

    Science.gov (United States)

    Papademetriou, Iason Titos

    Development of drug delivery systems (ie. nanocarriers) with controllable composition, architecture, and functionalities is heavily investigated in the field of drug delivery in order to improve clinical interventions. Designing drug nanocarriers which possess targeting properties is critical to enable them to reach the intended site of intervention in the body. To achieve this goal, the surface of drug nanocarriers can be modified with targeting moieties (antibodies, peptides, etc.) addressed to cell surface molecules expressed on the diseased tissues and cells. If these molecules are receptors capable of internalizing bound ligands via endocytosis, targeting can then enable drug transport into cells or across cellular barriers in the body. Yet, addressing nanocarriers to single targets presents limited control over cellular interactions and biodistribution. Since most cell-surface markers are not exclusively expressed in a precise site in vivo, high affinity of targeted nanocarriers may lead to non-desired accumulation in regions of the body associated with low expression. Modification of nanocarriers to achieve combined-targeting (binding to more than one cell-surface receptor) may help modulate binding to cells and also endocytosis, since cell receptors possess distinct functions and features affecting these parameters, such as their expression, location on the plasmalemma, activation in disease, mechanism of endocytosis, etc. Further, targeting nanocarriers to multiple epitopes of the same receptor, a strategy which has never been tested, may also modulate these parameters since they are highly epitope specific. In this dissertation, we investigate the effect of targeting model polymer nanocarriers to: (1) multiple receptors of similar function (intercellular-, platelet-endothelial-, and/or vascular-cell adhesion molecules), (2) multiple receptors of different function (intercellular adhesion molecule 1 and transferrin receptor), or (3) multiple epitopes of

  13. Increased statistical power with combined independent randomization tests used with multiple-baseline design.

    Science.gov (United States)

    Tyrrell, Pascal N; Corey, Paul N; Feldman, Brian M; Silverman, Earl D

    2013-06-01

    Physicians often assess the effectiveness of treatments on a small number of patients. Multiple-baseline designs (MBDs), based on the Wampold-Worsham (WW) method of randomization and applied to four subjects, have relatively low power. Our objective was to propose another approach with greater power that does not suffer from the time requirements of the WW method applied to a greater number of subjects. The power of a design that involves the combination of two four-subject MBDs was estimated using computer simulation and compared with the four- and eight-subject designs. The effect of a delayed linear response to treatment on the power of the test was also investigated. Power was found to be adequate (>80%) for a standardized mean difference (SMD) greater than 0.8. The effect size associated with 80% power from combined tests was smaller than that of the single four-subject MBD (SMD=1.3) and comparable with the eight-subject MBD (SMD=0.6). A delayed linear response to the treatment resulted in important reductions in power (20-35%). By combining two four-subject MBD tests, an investigator can detect better effect sizes (SMD=0.8) and be able to complete a comparatively timelier and feasible study. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. [Effectiveness of traumatic dislocation of knee joint combined with multiple ligament injuries treated by stages].

    Science.gov (United States)

    Chen, Zhiwei; Liu, Chunlei; Yang, Lezhong; Dai, Zhu; Cao, Shengjun

    2011-02-01

    To observe the effectiveness of traumatic dislocation of the knee joint combined with multiple ligament injuries treated by stages. Between june 2005 and November 2008, 13 cases of traumatic dislocation of the knee joint combined with multiple ligament injuries were treated by stages, including 9 males and 4 females with an average age of 30.7 years (range, 18-54 years). The dislocations were left knee in 3 cases and right knee in 10 cases. The causes of injury were sports injury in 8 cases, traffic accident injury in 2 cases, falling from height injury in 2 cases, and sprain injury in 1 case. The average time from injury to hospitalization was 9 hours (range, 6 hours to 2 days). Anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and medial collateral ligament (MCL) were involved in 8 cases; ACL, PCL, and lateral collateral ligament (LCL) in 3 cases; and ACL, PCL, MCL, and LCL in 2 cases. The valgus stress testing results of 10 knees were ++ to +++; the varus stress testing results of 5 knees were ++ to +++; all knees showed positive in the anterior or the posterior drawer test and ++ to +++ in Lachman test. The nerve, vessel, MCL, LCL, PCL, meniscus were repaired in the first operation. The functional exercise of knee joint was done after fixation for 3-4 weeks. During the second operation, the ACL was reconstructed under arthroscopy after the range of motion (ROM) of knee joint was good with anterior instability of knee within 4-6 months. All wounds healed by first intention after two operations; no complications of infection and compartment syndrome occurred. All cases were followed up 12-60 months with an average of 36 months. Joint effusion of knee occurred in 2 cases at 4 weeks after the first operation and was cured after removal of fluid. At 3 months after the second operation, the results of valgus stress testing and Lachman test were ++ in 1 case, respectively; the results of valgus stress testing, varus stress testing, and Lachman test

  15. EPSILON-CP: using deep learning to combine information from multiple sources for protein contact prediction.

    Science.gov (United States)

    Stahl, Kolja; Schneider, Michael; Brock, Oliver

    2017-06-17

    Accurately predicted contacts allow to compute the 3D structure of a protein. Since the solution space of native residue-residue contact pairs is very large, it is necessary to leverage information to identify relevant regions of the solution space, i.e. correct contacts. Every additional source of information can contribute to narrowing down candidate regions. Therefore, recent methods combined evolutionary and sequence-based information as well as evolutionary and physicochemical information. We develop a new contact predictor (EPSILON-CP) that goes beyond current methods by combining evolutionary, physicochemical, and sequence-based information. The problems resulting from the increased dimensionality and complexity of the learning problem are combated with a careful feature analysis, which results in a drastically reduced feature set. The different information sources are combined using deep neural networks. On 21 hard CASP11 FM targets, EPSILON-CP achieves a mean precision of 35.7% for top- L/10 predicted long-range contacts, which is 11% better than the CASP11 winning version of MetaPSICOV. The improvement on 1.5L is 17%. Furthermore, in this study we find that the amino acid composition, a commonly used feature, is rendered ineffective in the context of meta approaches. The size of the refined feature set decreased by 75%, enabling a significant increase in training data for machine learning, contributing significantly to the observed improvements. Exploiting as much and diverse information as possible is key to accurate contact prediction. Simply merging the information introduces new challenges. Our study suggests that critical feature analysis can improve the performance of contact prediction methods that combine multiple information sources. EPSILON-CP is available as a webservice: http://compbio.robotics.tu-berlin.de/epsilon/.

  16. Postcards from the imaging informatics road. Despite policy complexities, diagnostic imaging informatics makes progress on multiple fronts.

    Science.gov (United States)

    Hagland, Mark

    2011-11-01

    The current strategic landscape for imaging informatics is one filled with great contrasts and paradoxes. On the one hand, because imaging informatics was not explicitly addressed in Stage 1 of the meaningful use requirements under the American Recovery and Reinvestment Act/Health Information Technology for Economic and Clinical Health Act (ARRA-HITECH) legislation, it instantly lost some of the environment of turbo-charged energy characterized by areas that were directly addressed by the HITECH Act, such as quality data reporting, care management, and of course, core electronic health record (EHR) development. On the other hand, an interesting combination of factors--rapidly advancing technology, the expansion of the image archiving concept across different medical specialties, and the inclusion of diagnostic image-sharing as one element in the development of health information exchange (HIE) arrangements nationwide--is nonetheless pushing imaging informatics forward towards new innovations. The five articles below provide readers with different glimpses of the path ahead for imaging informatics. The first presents a look at the current policy and reimbursement landscape. Each of the four subsequent articles delve into different aspects of innovation, from a process developed at a public hospital to improve and speed up the diagnostic process for trauma patients, to a radiology-specific financial analytics solution in the group practice setting, to an advance in cardiology information systems, to a self-developed federated image viewing platform at one of the nation's largest integrated health systems. Each of those initiatives is very different; yet it is clear that a great deal of innovation is taking place across the US. healthcare system when it comes to imaging informatics. With a landscape filled with uncertainties and potential policy, reimbursement, and industry shifts in the offing, CIOs, CMIOs, and other healthcare IT leaders will need to think very

  17. Optical compression and encryption system combining multiple measurement matrices with fractional Fourier transform.

    Science.gov (United States)

    Yi, Jiawang; Tan, Guanzheng

    2015-12-20

    Optical cryptosystems combined with compressed sensing can achieve compression and encryption simultaneously. But they usually use the same measurement matrix to sample all blocks of an image, which makes it easy to estimate the measurement matrix in the chosen plaintext attack. In this paper, we propose a robust scheme adopting multiple measurement matrices to overcome this shortcoming. The matrices can be efficiently derived by applying random row exchanging to a basic one, which is also encoded into the fractional Fourier transform (FrFT) domain to improve the visual effect of wrongly decrypted images. Chaos-based pixel scrambling is added into our double FrFT cryptosystem to guarantee its nonlinearity. Simulation results have shown the security and effectiveness of our scheme.

  18. Review: Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training

    DEFF Research Database (Denmark)

    Dalgas, U; Stenager, E; Ingemann-Hansen, T

    2008-01-01

    of an inactive lifestyle. To date the effects of exercise have only been studied in moderately impaired MS patients with an EDSS score of less than 7. Evidence exists for recommending participation in endurance training at low to moderate intensity, as the existing literature demonstrates that MS patients can...... both tolerate and benefit from this training modality. Also, resistance training of moderate intensity seems to be well tolerated and to have beneficial effects on MS patients, but the methodological quality of the existing evidence is in general low and the number of studies is limited. Only two...... studies have evaluated the effects of combined resistance- and endurance training, making solid conclusions regarding this training modality impossible. Multiple Sclerosis 2008; 14: 35-53. http://msj.sagepub.com. Udgivelsesdato: 2008-Jan...

  19. Using Multiple Antibiotic Resistance Profiles of Coliforms as a Tool to Investigate Combined Sewer Overflow Contamination.

    Science.gov (United States)

    Dhiman, Gaurav; Burns, Emma N; Morris, David W

    2016-10-01

    Studies have shown that fecal contamination can be determined by conducting multiple antibiotic resistance (MAR) analyses. The hypothesis is if bacteria exhibit resistance, they are likely to be derived from organisms exposed to antimicrobial agents. Therefore, this project seeks to apply MAR analysis to nonpoint source (NPS) and combined sewer overflow (CSO) areas along the Anacostia River in Washington, DC. Presumptive E. coli was isolated from NPS and CSO samples and tested with eight different antimicrobial agents to assess MAR indices. Isolates from CSO sources showed significantly greater resistance (p coliforms are associated with CSO overflows, indicating that pollution-derived coliform levels are strongly linked to antimicrobial resistance. The implementation of this method as an index for water quality in the remediation of the Anacostia River has the ability to serve as a model and monitoring tool for the rehabilitation of urban watersheds.

  20. Mosaicism for genome-wide paternal uniparental disomy with features of multiple imprinting disorders: diagnostic and management issues.

    Science.gov (United States)

    Inbar-Feigenberg, Michal; Choufani, Sanaa; Cytrynbaum, Cheryl; Chen, Yi-An; Steele, Leslie; Shuman, Cheryl; Ray, Peter N; Weksberg, Rosanna

    2013-01-01

    Mosaicism for genome-wide paternal uniparental disomy (UPD) has been reported in only seven live born individuals to date. Clinical presentation includes manifestations of multiple paternal UPD syndromes with high variability, likely due to the variable levels of mosaicism in different somatic tissues. We report an eighth case in a female patient with mosaicism for genome-wide paternal UPD which highlights the complex clinical presentation. Our patient had features of Beckwith-Wiedemann syndrome (BWS), Angelman syndrome, and congenital hyperinsulinism. The clinical findings included prematurity, organomegaly, hemihyperplasia, developmental delay, benign tumors, and cystic lesions. The diagnosis in our patient was established utilizing microarray-based genome-wide DNA methylation analysis performed on leukocyte DNA. Targeted multiplex ligation-dependent probe amplification (MLPA) analysis of chromosome regions 11p15 and 15q13 confirmed mosaicism for paternal UPD at these genomic regions. This case represents the first report of microarray-based genome-wide DNA methylation analysis in the diagnosis of genome-wide paternal UPD. The application of microarray-based genome-wide DNA methylation analysis on selected individuals with complex clinical presentations could be a valuable diagnostic tool to improve the detection rate of mosaic genome-wide paternal UPD. This approach, which screens many loci simultaneously, is more cost-effective and less labor-intensive than performing multiple targeted DNA methylation-based assays. Identification of individuals with mosaicism for genome-wide paternal UPD is an important goal as it confers a low recurrence risk for the family and identifies individuals who require surveillance due to increased tumor risk. Copyright © 2012 Wiley Periodicals, Inc.

  1. Self-Healing Gelatin Hydrogels Cross-Linked by Combining Multiple Hydrogen Bonding and Ionic Coordination.

    Science.gov (United States)

    Zhang, Guangzhao; Lv, Lei; Deng, Yonghong; Wang, Chaoyang

    2017-06-01

    Self-healing hydrogels have been studied by many researchers via multiple cross-linking approaches including physical and chemical interactions. It is an interesting project in multifunctional hydrogel exploration that a water soluble polymer matrix is cross-linked by combining the ionic coordination and the multiple hydrogen bonds to fabricate self-healing hydrogels with injectable property. This study introduces a general procedure of preparing the hydrogels (termed gelatin-UPy-Fe) cross-linked by both ionic coordination of Fe3+ and carboxyl group from the gelatin and the quadruple hydrogen bonding interaction from the ureido-pyrimidinone (UPy) dimers. The gelatin-UPy-Fe hydrogels possess an excellent self-healing property. The effects of the ionic coordination of Fe3+ and quadruple hydrogen bonding of UPy on the formation and mechanical behavior of the prepared hydrogels are investigated. In vitro drug release of the gelatin-UPy-Fe hydrogels is also observed, giving an intriguing glimpse into possible biological applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Conceptual study of SCRUM and CCPM combined application in multiple project flexible management

    Directory of Open Access Journals (Sweden)

    Ilton Marchi de Almeida

    2016-11-01

    Full Text Available Project Management (PM has gained a major role in the viability of organizational strategic objectives. The development of products and services has been under increasing market pressure, demanding frequent releases in ever-shorter time periods. To meet these new requirements, PM has to provide the information needed to make decisions in multiple complex projects that are exposed to uncertainty and volatility. Regarding the opportunities to improve PM practices in order to deal with this unstable and ambiguous environment, the aim of this paper is to propose, by means of a conceptual literature analysis, the combined application of two PM methodologies: Critical Chain Project Management (CCPM, and SCRUM. The results of this study indicate that integration of these methodologies can enhance the benefits and mitigate the weaknesses of each of them. This hybrid model could enable better articulation and coordination of project tasks, allowing more effective decisions to be made in multiple project environments affected by volatility, uncertainty, complexity and ambiguity (VUCA.

  3. Development and Application of a Two-Tier Multiple Choice Diagnostic Instrument To Assess High School Students' Understanding of Inorganic Chemistry Qualitative Analysis.

    Science.gov (United States)

    Tan, Kim Chwee Daniel; Goh, Ngoh Khang; Chia, Lian Sai; Treagust, David F.

    2002-01-01

    Describes the development and application of a two-tier multiple choice diagnostic instrument to assess high school students' understanding of inorganic chemistry qualitative analysis. Shows that the Grade 10 students had difficulty understanding the reactions involved in the identification of cations and anions, for example, double decomposition…

  4. More Than Just Accuracy: A Novel Method to Incorporate Multiple Test Attributes in Evaluating Diagnostic Tests Including Point of Care Tests.

    Science.gov (United States)

    Thompson, Matthew; Weigl, Bernhard; Fitzpatrick, Annette; Ide, Nicole

    2016-01-01

    Current frameworks for evaluating diagnostic tests are constrained by a focus on diagnostic accuracy, and assume that all aspects of the testing process and test attributes are discrete and equally important. Determining the balance between the benefits and harms associated with new or existing tests has been overlooked. Yet, this is critically important information for stakeholders involved in developing, testing, and implementing tests. This is particularly important for point of care tests (POCTs) where tradeoffs exist between numerous aspects of the testing process and test attributes. We developed a new model that multiple stakeholders (e.g., clinicians, patients, researchers, test developers, industry, regulators, and health care funders) can use to visualize the multiple attributes of tests, the interactions that occur between these attributes, and their impacts on health outcomes. We use multiple examples to illustrate interactions between test attributes (test availability, test experience, and test results) and outcomes, including several POCTs. The model could be used to prioritize research and development efforts, and inform regulatory submissions for new diagnostics. It could potentially provide a way to incorporate the relative weights that various subgroups or clinical settings might place on different test attributes. Our model provides a novel way that multiple stakeholders can use to visualize test attributes, their interactions, and impacts on individual and population outcomes. We anticipate that this will facilitate more informed decision making around diagnostic tests.

  5. Non-invasive diagnostic system and its opto-mechanical probe for combining confocal Raman spectroscopy and optical coherence tomography.

    Science.gov (United States)

    Klemes, Jan; Kotzianova, Adela; Pokorny, Marek; Mojzes, Peter; Novak, Jindrich; Sukova, Lada; Demuth, Jaroslav; Vesely, Jaroslav; Sasek, Ladislav; Velebny, Vladimir

    2017-11-01

    Non-invasive optical diagnostic methods allow important information about studied systems to be obtained in a non-destructive way. Complete diagnosis requires information about the chemical composition as well as the morphological structure of a sample. We report on the development of an opto-mechanical probe that combines Raman spectroscopy (RS) and optical coherence tomography (OCT), two methods that provide all the crucial information needed for a non-invasive diagnosis. The aim of this paper is to introduce the technical design, construction and optimization of a dual opto-mechanical probe combining two in-house developed devices for confocal RS and OCT. The unique benefit of the probe is a gradual acquisition of OCT and RS data, which allows to use the acquired OCT images to pinpoint locations of interest for RS measurements. The parameters and the correct functioning of the probe were verified by RS scanning of various samples (silicon wafer and ex vivo tissue) based on their OCT images - lateral as well as depth scanning was performed. Both the OCT and RS systems were developed, optimized and tested with the ultimate aim of verifying the functionality of the probe. Picture: Schematic illustration and visualization of the developed RS-OCT probe. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Positron emission tomography-computed tomography in the diagnostic evaluation of smoldering multiple myeloma: identification of patients needing therapy.

    Science.gov (United States)

    Siontis, B; Kumar, S; Dispenzieri, A; Drake, M T; Lacy, M Q; Buadi, F; Dingli, D; Kapoor, P; Gonsalves, W; Gertz, M A; Rajkumar, S V

    2015-10-23

    We studied 188 patients with a suspected smoldering multiple myeloma (MM) who had undergone a positron emission tomography-computed tomography (PET-CT) scan as part of their clinical evaluation. PET-CT was positive (clinical radiologist interpretation of increased bone uptake and/or evidence of lytic bone destruction) in 74 patients and negative in 114 patients. Of these, 25 patients with a positive PET-CT and 97 patients with a negative PET-CT were observed without therapy and formed the study cohort (n=122). The probability of progression to MM within 2 years was 75% in patients with a positive PET-CT observed without therapy compared with 30% in patients with a negative PET-CT; median time to progression was 21 months versus 60 months, respectively, P=0.0008. Of 25 patients with a positive PET-CT, the probability of progression was 87% at 2 years in those with evidence of underlying osteolysis (n=16) and 61% in patients with abnormal PET-CT uptake but no evidence of osteolysis (n=9). Patients with positive PET-CT and evidence of underlying osteolysis have a high risk of progression to MM within 2 years when observed without therapy. These observations support recent changes to imaging requirements in the International Myeloma Working Group updated diagnostic criteria for MM.

  7. The diagnostic utility of combination of HMGA2 and IMP3 qRT-PCR testing in thyroid neoplasms.

    Science.gov (United States)

    Jin, Long; Lloyd, Ricardo V; Henry, Michael R; Erickson, Lori A; Sebo, Thomas J; Rumilla, Kandelaria M; Zhang, Jun

    2015-01-01

    The diagnosis of malignant thyroid tumors in some cytologic and histologic specimens remains challenging. High-mobility group A2 (HMGA2) expression and insulin-like growth factor II mRNA-binding protein-3 (IMP3) expression were evaluated by relative quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The aim of this study was to evaluate whether the combination of HMGA2 and IMP3 qRT-PCR was diagnostically useful in differentiating benign from malignant thyroid neoplasms. Fine-needle aspiration (FNA) specimens from 120 patients including 56 benign lesions and 64 carcinomas were used. The available 80 corresponding formalin-fixed paraffin-embedded (FFPE) thyroid tissues from 66 patients were also included in this study. HMGA2 and IMP3 expression levels were detected by qRT-PCR and reported as relative fold change after normalizing with a calibrator. The diagnostic utilities of HMGA2 and IMP3 qRT-PCR tests were evaluated individually and in combination. In FNA specimens, HMGA2 and IMP3 expression was consistently higher in thyroid malignancies compared with benign lesions in all subgroups except in Hürthle cell tumors. After exclusion of Hürthle cell tumors, the sensitivity was 90.2% for HMGA2, 88.2% for IMP3, and 98% for HMGA2+IMP3; the specificity was 97.1% for HMGA2, 79.4% for IMP3, and 79.4% for HMGA+IMP3. qRT-PCR data showed similar results in FFPE tissues: the sensitivity was 84.2% for HMGA2, 85.7% for IMP3, and 94.7% for HMGA2+IMP3; the specificity was 96.9% for HMGA2, 91.2% for IMP3, and 90.6% for HMGA2+IMP3. qRT-PCR data were concordant between FNA and FFPE samples for HMGA2 (97.4%) and IMP3 (96.9%). The results indicate that HMGA2 qRT-PCR with high specificity may be a useful ancillary technique to assist in the classification of difficult thyroid specimens, excluding Hürthle cell tumors. The HMGA2 and IMP3 qRT-PCR combination model with increased sensitivity and negative predictive value (96.4%) may be useful in screening thyroid

  8. Combined visual and motor evoked potentials predict multiple sclerosis disability after 20 years.

    Science.gov (United States)

    Schlaeger, Regina; Schindler, Christian; Grize, Leticia; Dellas, Sophie; Radue, Ernst W; Kappos, Ludwig; Fuhr, Peter

    2014-09-01

    The development of predictors of multiple sclerosis (MS) disability is difficult due to the complex interplay of pathophysiological and adaptive processes. The purpose of this study was to investigate whether combined evoked potential (EP)-measures allow prediction of MS disability after 20 years. We examined 28 patients with clinically definite MS according to Poser's criteria with Expanded Disability Status Scale (EDSS) scores, combined visual and motor EPs at entry (T0), 6 (T1), 12 (T2) and 24 (T3) months, and a cranial magnetic resonance imaging (MRI) scan at T0 and T2. EDSS testing was repeated at year 14 (T4) and year 20 (T5). Spearman rank correlation was used. We performed a multivariable regression analysis to examine predictive relationships of the sum of z-transformed EP latencies (s-EPT0) and other baseline variables with EDSST5. We found that s-EPT0 correlated with EDSST5 (rho=0.72, pdisability in MS. © The Author(s) 2014.

  9. Atomic Theory and Multiple Combining Proportions: The Search for Whole Number Ratios.

    Science.gov (United States)

    Usselman, Melvyn C; Brown, Todd A

    2015-04-01

    John Dalton's atomic theory, with its postulate of compound formation through atom-to-atom combination, brought a new perspective to weight relationships in chemical reactions. A presumed one-to-one combination of atoms A and B to form a simple compound AB allowed Dalton to construct his first table of relative atomic weights from literature analyses of appropriate binary compounds. For such simple binary compounds, the atomic theory had little advantages over affinity theory as an explanation of fixed proportions by weight. For ternary compounds of the form AB2, however, atomic theory made quantitative predictions that were not deducible from affinity theory. Atomic theory required that the weight of B in the compound AB2 be exactly twice that in the compound AB. Dalton, Thomas Thomson and William Hyde Wollaston all published within a few years of each other experimental data that claimed to give the predicted results with the required accuracy. There are nonetheless several experimental barriers to obtaining the desired integral multiple proportions. In this paper I will discuss replication experiments which demonstrate that only Wollaston's results are experimentally reliable. It is likely that such replicability explains why Wollaston's experiments were so influential.

  10. Smart Sensor for Online Detection of Multiple-Combined Faults in VSD-Fed Induction Motors

    Science.gov (United States)

    Garcia-Ramirez, Armando G.; Osornio-Rios, Roque A.; Granados-Lieberman, David; Garcia-Perez, Arturo; Romero-Troncoso, Rene J.

    2012-01-01

    Induction motors fed through variable speed drives (VSD) are widely used in different industrial processes. Nowadays, the industry demands the integration of smart sensors to improve the fault detection in order to reduce cost, maintenance and power consumption. Induction motors can develop one or more faults at the same time that can be produce severe damages. The combined fault identification in induction motors is a demanding task, but it has been rarely considered in spite of being a common situation, because it is difficult to identify two or more faults simultaneously. This work presents a smart sensor for online detection of simple and multiple-combined faults in induction motors fed through a VSD in a wide frequency range covering low frequencies from 3 Hz and high frequencies up to 60 Hz based on a primary sensor being a commercially available current clamp or a hall-effect sensor. The proposed smart sensor implements a methodology based on the fast Fourier transform (FFT), RMS calculation and artificial neural networks (ANN), which are processed online using digital hardware signal processing based on field programmable gate array (FPGA).

  11. Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy.

    Science.gov (United States)

    Berenson, J R; Hilger, J D; Yellin, O; Dichmann, R; Patel-Donnelly, D; Boccia, R V; Bessudo, A; Stampleman, L; Gravenor, D; Eshaghian, S; Nassir, Y; Swift, R A; Vescio, R A

    2014-07-01

    In this open-label, intra-patient phase I/II trial, bortezomib was replaced with carfilzomib (escalated from 20 to 45 mg/m(2) on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle) for multiple myeloma (MM) patients who progressed while on or within 12 weeks of receiving a bortezomib-containing combination regimen. Study objectives included determination of the maximum tolerated dose (MTD), overall response rate (ORR), clinical benefit rate (CBR), time to progression, time to response, duration of response, progression-free survival and overall survival (OS). Of 38 registered patients, 37 were treated and evaluable for efficacy and safety. Thirty-one carfilzomib-based regimens using 14 different drug combinations were tested. One regimen (carfilzomib (45 mg/m(2)), ascorbic acid (1000 mg) and cyclophosphamide (2.2 mg/kg)) reached MTD. ORR and CBR were 43.2 and 62.2%, respectively. Median progression-free survival, time to progression and OS were 8.3, 9.9 and 15.8 months, respectively. Hematologic adverse events (AEs; ⩾grade 3) included lymphopenia (35.1%), thrombocytopenia (24.3%), anemia (10.8%) and neutropenia (10.8%). Nonhematologic AEs (⩾grade 3) included fever (5.4%) and hypokalemia (5.4%). These results demonstrate that replacing bortezomib with carfilzomib is safe and can be effective for MM patients failing bortezomib-containing combination regimens. This trial was registered at http://www.clinicaltrials.gov (#NCT01365559).

  12. Combined use of Kappa Free Light Chain Index and Isoelectrofocusing of Cerebro-Spinal Fluid in Diagnosing Multiple Sclerosis: Performances and Costs.

    Science.gov (United States)

    Crespi, Ilaria; Sulas, Maria Giovanna; Mora, Riccardo; Naldi, Paola; Vecchio, Domizia; Comi, Cristoforo; Cantello, Roberto; Bellomo, Giorgio

    2017-03-01

    Isoelectrofocusing (IEF) to detect oligoclonal bands (OBCs) in cerebrospinal fluid (CSF) is the gold standard approach for evaluating intrathecal immunoglobulin synthesis in multiple sclerosis (MS) but the kappa free light chain index (KFLCi) is emerging as an alternative marker, and the combined/sequential uses of IEF and KFLCi have never been challenged. CSF and serum albumin, IgG, kFLC and lFLC were measured by nephelometry; albumin, IgG and kFLC quotients as well as Link and kFLC indexes were calculated; OCBs were evaluated by immunofixation. A total of 150 consecutive patients: 48 with MS, 32 with other neurological inflammatory diseases (NID), 62 with neurological non-inflammatory diseases (NNID), and 8 without any detectable neurological disease (NND) were investigated. Both IEF and KFLCi showed a similar accuracy as diagnostic tests for multiple sclerosis. The high sensitivity and specificity associated with the lower cost of KFLCi suggested to use this test first, followed by IEF as a confirmative procedure. The sequential use of IEF and KFLCi showed high diagnostic efficiency with cost reduction of 43 and 21%, if compared to the contemporary use of both tests, or the unique use of IEF in all patients. The "sequential testing" using KFLCi followed by IEF in MS represents an optimal procedure with accurate performance and lower costs.

  13. Combined RASSF1A and RASSF2A Promoter Methylation Analysis as Diagnostic Biomarker for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Wei Meng

    2012-01-01

    Full Text Available Promoter hypermethylation, a widely studied epigenetic event known to influence gene expression levels, has been proposed as a potential biomarker in multiple types of cancer. Clinical diagnostic biomarkers are needed for reliable prediction of bladder cancer recurrence. In this paper, DNA promoter methylation of five C-terminal Ras-association family members (RASSF1A, RASSF2A, RASSF4, RASSF5, and RASSF6 was studied in 64 formalin-fixed paraffin-embedded (FFPE bladder cancer and normal adjacent tissues using methylation-specific high-resolution melting (MS-HRM analysis. Results showed that 73% (30/41 of transitional cell carcinoma, 100% (3/3 of squamous cell carcinoma, and 100% (4/4 of small cell carcinoma demonstrated promoter methylation of the RASSF1A or RASSF2A gene, but only 6% (1/16 of normal tissues had promoter methylation of RASSF genes. Testing positive for hypermethylation of RASSF1A or RASSF2A promoter provided 77% sensitivity and 94% specificity for identification of cancer tissues with an area under the curve of 0.854, suggesting that promoter methylation analysis of RASSF1A and RASSF2A genes has potential for use as a recurrence biomarker for bladder cancer patients.

  14. Meaning and challenges in the practice of multiple therapeutic massage modalities: a combined methods study

    Directory of Open Access Journals (Sweden)

    Page Stacey A

    2011-09-01

    Full Text Available Abstract Background Therapeutic massage and bodywork (TMB practitioners are predominantly trained in programs that are not uniformly standardized, and in variable combinations of therapies. To date no studies have explored this variability in training and how this affects clinical practice. Methods Combined methods, consisting of a quantitative, population-based survey and qualitative interviews with practitioners trained in multiple therapies, were used to explore the training and practice of TMB practitioners in Alberta, Canada. Results Of the 5242 distributed surveys, 791 were returned (15.1%. Practitioners were predominantly female (91.7%, worked in a range of environments, primarily private (44.4% and home clinics (35.4%, and were not significantly different from other surveyed massage therapist populations. Seventy-seven distinct TMB therapies were identified. Most practitioners were trained in two or more therapies (94.4%, with a median of 8 and range of 40 therapies. Training programs varied widely in number and type of TMB components, training length, or both. Nineteen interviews were conducted. Participants described highly variable training backgrounds, resulting in practitioners learning unique combinations of therapy techniques. All practitioners reported providing individualized patient treatment based on a responsive feedback process throughout practice that they described as being critical to appropriately address the needs of patients. They also felt that research treatment protocols were different from clinical practice because researchers do not usually sufficiently acknowledge the individualized nature of TMB care provision. Conclusions The training received, the number of therapies trained in, and the practice descriptors of TMB practitioners are all highly variable. In addition, clinical experience and continuing education may further alter or enhance treatment techniques. Practitioners individualize each patient

  15. Combined use of fine-needle aspiration biopsy, MIBI scans and frozen section biopsy offers the best diagnostic accuracy in the assessment of the hypofunctioning solitary thyroid nodule

    Energy Technology Data Exchange (ETDEWEB)

    Hurtado-Lopez, Luis Mauricio; Arellano-Montano, Sara; Torres-Acosta, Evelyn Migdalia; Zaldivar-Ramirez, Felipe Rafael; Duarte-Torres, Reyna Margarita; Alonso-de-Ruiz, Patricia; Martinez-Duncker, Ivan [Thyroid Clinic, General Hospital of Mexico, Mexico City (Mexico); Martinez-Duncker, Carlos [Thyroid Clinic, General Hospital of Mexico, Mexico City (Mexico); Molecular Nuclear Medicine, Hospital Infantil de Mexico, Mexico (Mexico)

    2004-09-01

    The probability of malignancy is increased in hypofunctioning solitary thyroid nodules (HFNs). Fine-needle aspiration biopsy (FNA), {sup 99m}Tc-methoxyisobutylisonitrile (MIBI) and frozen section biopsy (FS) have limited independent diagnostic accuracy for the differential diagnosis of HFNs. The goal of this study was to assess the accuracy of the three independent diagnostic methods in distinguishing between benign and malignant disease. A total of 130 patients with an HFN on the {sup 99m}Tc-pertechnetate scan were included in this study. FNA, MIBI scans, FS, thyroidectomy and histological analysis of surgical specimens for final diagnosis were performed in all patients. Of the 130 patients, 80 (61.54%) had benign lesions and 50 (38.46%), malignant lesions. FNA was diagnostic in 78/130 (60%) patients and non-diagnostic in 52/130 (40%) patients. None of the patients with a negative MIBI scan had a final histological diagnosis of malignancy, and MIBI scans were negative in 38.46% of patients with non-diagnostic FNA results. FS was diagnostic in 104/130 (80%) patients and non-diagnostic in 26/130 (20%) patients. Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios were 81.3%, 97.8%, 96%, 88%, 36.95 and 0.19 respectively for FNA; 100%, 61.3%, 61.7%, 100%, 2.58 and 0 respectively for MIBI; and 80.5%, 100%, 100%, 89%, 0 and 0.2 respectively for FS. Use of both MIBI scans and FS in patients with non-diagnostic FNA rendered a specificity and sensitivity of 100%. MIBI scans exclude malignancy in a significant proportion of patients with non-diagnostic FNAs (38% in this study). Cystic nodules with a positive MIBI scan should be further investigated even when the FNA result indicates a benign lesion. Combined use of FNA, MIBI and FS offers the best diagnostic accuracy. (orig.)

  16. A Novel Electrochemical Microfluidic Chip Combined with Multiple Biomarkers for Early Diagnosis of Gastric Cancer

    Science.gov (United States)

    Xie, Yao; Zhi, Xiao; Su, Haichuan; Wang, Kan; Yan, Zhen; He, Nongyue; Zhang, Jingpu; Chen, Di; Cui, Daxiang

    2015-12-01

    Early diagnosis is very important to improve the survival rate of patients with gastric cancer and to understand the biology of cancer. In order to meet the clinical demands for early diagnosis of gastric cancer, we developed a disposable easy-to-use electrochemical microfluidic chip combined with multiple antibodies against six kinds of biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), Helicobacter pylori CagA protein (H.P.), P53oncoprotein (P53), pepsinogen I (PG I), and PG-II). The six kinds of biomarkers related to gastric cancer can be detected sensitively and synchronously in a short time. The specially designed three electrodes system enables cross-contamination to be avoided effectively. The linear ranges of detection of the electrochemical microfluidic chip were as follows: 0.37-90 ng mL-1 for CEA, 10.75-172 U mL-1 for CA19-9, 10-160 U L-1 for H.P., 35-560 ng mL-1 for P53, 37.5-600 ng mL-1 for PG I, and 2.5-80 ng mL-1for PG II. This method owns better sensitivity compared with enzyme-linked immunosorbent assay (ELISA) results of 394 specimens of gastric cancer sera. Furthermore, we established a multi-index prediction model based on the six kinds of biomarkers for predicting risk of gastric cancer. In conclusion, the electrochemical microfluidic chip for detecting multiple biomarkers has great potential in applications such as early screening of gastric cancer patients, and therapeutic evaluation, and real-time dynamic monitoring the progress of gastric cancer in near future.

  17. How to combine multiple techniques to provide reliable in-situ time series for climate applications

    Science.gov (United States)

    Valladeau, G.; Soudarin, L.; Gravelle, M.

    2012-12-01

    Tide gauge measurements, as observations dedicated to climate applications, require a rigorous quality control since measurements are highly sensitive to biases or drifts in datasets. One major part of the error related to the assessment of Sea Surface Height at tide gauge location originates in vertical movements. Indeed, many studies have for instance demonstrated the need for tide gauges to be corrected for land motion when compared with altimeter data. The combination of multiple techniques (altimeter, in-situ and geodetic data) is a way of providing relevant tide gauge time series for end-users and climate applications such as the contribution of ice-sheet mass balance to the global sea-level. In this way, DORIS (Doppler Orbitography and Radiopositioning Integrated by Satellite) as well as GNSS (Global Navigation Satellite System) are considered as complementary techniques. They determine the crustal motion at a cm (or better) and mm/yr accuracy for the positions and velocities respectively. As the DORIS network was deployed by a geodetic institution, great care was taken when selecting the geographical location of the tracking stations to co-locate them with other space geodetic techniques (VLBI, SLR and GNSS), but also with tide gauges. Hence, as on May 2012, 22 DORIS stations are within 10 km from a tide gauge, including 8 within 500m. Ties between the DORIS antennas and the nearby tide gauge are also available when the measurement is possible. This study focuses on the example of the Thule tide gauge for which measurements are compared to the different techniques previously described. First, the comparison to both DORIS and GNSS data provides relevant information about the strong crustal movement North of Greenland. Then the use of altimeter data confirms results deduced from geodetic stations and give a larger view on the behavior of land motion around the Thule tide gauge. Therefore, the combination of multiple techniques is used to provide reliable tide

  18. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach.

    Directory of Open Access Journals (Sweden)

    Scott R Fry

    2011-06-01

    Full Text Available BACKGROUND: Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1 has been identified as an early marker for acute dengue, and is typically present between days 1-9 post-onset of illness but following seroconversion it can be difficult to detect in serum. AIMS: To evaluate the performance of a newly developed Panbio® Dengue Early Rapid test for NS1 and determine if it can improve diagnostic sensitivity when used in combination with a commercial IgM/IgG rapid test. METHODOLOGY: The clinical performance of the Dengue Early Rapid was evaluated in a retrospective study in Vietnam with 198 acute laboratory-confirmed positive and 100 negative samples. The performance of the Dengue Early Rapid in combination with the IgM/IgG Rapid test was also evaluated in Malaysia with 263 laboratory-confirmed positive and 30 negative samples. KEY RESULTS: In Vietnam the sensitivity and specificity of the test was 69.2% (95% CI: 62.8% to 75.6% and 96% (95% CI: 92.2% to 99.8 respectively. In Malaysia the performance was similar with 68.9% sensitivity (95% CI: 61.8% to 76.1% and 96.7% specificity (95% CI: 82.8% to 99.9% compared to RT-PCR. Importantly, when the Dengue Early Rapid test was used in combination with the IgM/IgG test the sensitivity increased to 93.0%. When the two tests were compared at each day post-onset of illness there was clear differentiation between the antigen and antibody markers. CONCLUSIONS: This study highlights that using dengue NS1 antigen detection in combination with anti-glycoprotein E IgM and IgG serology can significantly increase the sensitivity of acute dengue diagnosis and extends the possible window of detection to include very early acute samples and enhances the clinical utility of rapid immunochromatographic testing for dengue.

  19. Combined PET/MRI in cerebral and paediatric diagnostics; Kombinierte PET/MRT-Diagnostik bei zerebralen und paediatrischen Fragestellungen

    Energy Technology Data Exchange (ETDEWEB)

    Pfluger, T.; Vollmar, C.; Porn, U.; Schmid, R.; Dresel, S.; Leinsinger, G.; Schmid, I.; Winkler, P.; Fischer, S.; Hahn, K. [Klinik und Poliklinik fuer Nuklearmedizin, Ludwig-Maximilians-Univ. Muenchen (Germany)

    2002-07-01

    The aim of this overview is presentation of MRI and PET as synergistic modalities for combined analysis of morphology and function. For operative planning in epilepsy surgery, definition of the epileptogenic focus based on functional PET diagnostics and morphological MRI is decisive. For staging and follow-up examinations in oncology, MRI should be complemented by PET for the assessment of tumor vitality. In paediatric oncology patients we could demonstrate a therapy relevant increase of sensitivity/specificity with combined PET/MRI in contrast to single modalities. In the brain, full spectrum of digital image registration and three-dimensional reconstruction should be used. In extracranial cases, image fusion is disturbing due to a partial loss of image information of single modalities by the fusion process. (orig.) [German] Ziel dieser Uebersicht ist die Darstellung der MRT und PET als synergistische Verfahren zur Analyse von Morphologie und Funktion. Zur Resektionsplanung im Rahmen der Epilepsiechirurgie ist die Definition des Epilepsiefokus anhand der funktionellen PET-Diagnostik und die exakte Kenntnis der zerebralen Morphologie aus der MRT ganz entscheidend. Im Rahmen des onkologischen Stagings und bei Verlaufskontrollen ist wegen der geringeren Spezifitaet der MRT die additive PET zur Beurteilung der Tumorvitalitaet erforderlich. Anhand eines paediatrisch-onkologischen Patientengutes konnten wir zeigen, dass mit der kombinierten PET/MRT-Diagnostik eine therapierelevante Steigerung der Sensitivitaet/Spezifitaet gegenueber den Einzeluntersuchungen moeglich ist. Bei zerebralen Fragestellungen sollte das gesamte Spektrum der digitalen Bildfusion mit direkter Ueberlagerung mehrerer Modalitaeten und anschliessender dreidimensionaler Rekonstruktion ausgeschoepft werden. Bei extrakraniellen Fragestellungen ist die direkte Bildueberlagerung eher hinderlich, da die Bildinformation der Einzelmodalitaeten durch die Fusion teilweise verloren geht. (orig.)

  20. Analysis of single blood cells for CSF diagnostics via a combination of fluorescence staining and micro-Raman spectroscopy.

    Science.gov (United States)

    Harz, Michaela; Kiehntopf, Michael; Stöckel, Stephan; Rösch, Petra; Deufel, Thomas; Popp, Jürgen

    2008-10-01

    This contribution provides a new approach for single blood cell analysis in cerebrospinal fluid (CSF) with the possibility of utilizing simultaneously on the same sample the unique capabilities of the two methods fluorescence staining and Raman spectroscopy. By doing so this technique enables the potential of accurate and rapid cell identification in order to determine cell parameters immediately (e.g. the study of the level of activation or phagocytosis activity of single blood cells). Fluorescence labeling of blood cells offers the great possibility of differentiating easily between the subtypes of white blood cells, while Raman spectroscopy reveals molecular fingerprint information with a spatial resolution down to the diffraction limit. Compared to an unstained cell, the presented results nicely demonstrate that the selected fluorescence dye does not influence the Raman spectrum of a labeled blood cell notably. By the combined application of Raman spectroscopy and statistical data analysis a distinction between white blood cell substructures could be performed. Since several blood cell types also differ in the amount of their cell components, differentiation between several blood cell types is also possible when one blood cell is described in the database by several Raman spectra according their presented sub-microscopic structures. This capability with the possibility of accurate and rapid blood cell identification in cerebrospinal fluid is extremely promising for implementation in clinical diagnostics.

  1. Combination of various data analysis techniques for efficient track reconstruction in very high multiplicity events

    Science.gov (United States)

    Siklér, Ferenc

    2017-08-01

    A novel combination of established data analysis techniques for reconstructing charged-particles in high energy collisions is proposed. It uses all information available in a collision event while keeping competing choices open as long as possible. Suitable track candidates are selected by transforming measured hits to a binned, three- or four-dimensional, track parameter space. It is accomplished by the use of templates taking advantage of the translational and rotational symmetries of the detectors. Track candidates and their corresponding hits, the nodes, form a usually highly connected network, a bipartite graph, where we allow for multiple hit to track assignments, edges. In order to get a manageable problem, the graph is cut into very many minigraphs by removing a few of its vulnerable components, edges and nodes. Finally the hits are distributed among the track candidates by exploring a deterministic decision tree. A depth-limited search is performed maximizing the number of hits on tracks, and minimizing the sum of track-fit χ2. Simplified but realistic models of LHC silicon trackers including the relevant physics processes are used to test and study the performance (efficiency, purity, timing) of the proposed method in the case of single or many simultaneous proton-proton collisions (high pileup), and for single heavy-ion collisions at the highest available energies.

  2. The diagnostic value of the combination of patient characteristics, history, and clinical shoulder tests for the diagnosis of rotator cuff tear

    NARCIS (Netherlands)

    van Kampen, D.A.; van den Berg, T.; van der Woude, H.J.; Castelein, R.M.; Scholtes, V.A.B.; Terwee, C.B.; Willems, W.J.

    2014-01-01

    Background: It is unknown which combination of patient information and clinical tests might be optimal for the diagnosis of rotator cuff tears. This study aimed to determine the diagnostic value of nine individual clinical tests for evaluating rotator cuff tear and to develop a prediction model for

  3. A noninvasive multi-analyte diagnostic assay: Combining protein and DNA markers to stratify bladder cancer patients

    NARCIS (Netherlands)

    C.A. Fernandez (Cecilia A); J.M. Millholland (John M); E.C. Zwarthoff (Ellen); A.S. Feldman (Adam S); R.J. Karnes (Jeffrey); A.P. Shuber (Anthony P)

    2012-01-01

    textabstractPurpose: The authors recently reported the development of a noninvasive diagnostic assay using urinary matrix metalloproteinases (MMPs) as monitors of disease-free status and bladder cancer in high-risk populations. Using an approach called clinical intervention determining diagnostic

  4. Improving multiple-point-based a priori models for inverse problems by combining Sequential Simulation with the Frequency Matching Method

    DEFF Research Database (Denmark)

    Cordua, Knud Skou; Hansen, Thomas Mejer; Lange, Katrine

    .e. marginals) of the training image and a subsurface model are matched in order to obtain a solution with the same multiple-point statistics as the training image. Sequential Gibbs sampling is a simulation strategy that provides an efficient way of applying sequential simulation based algorithms as a priori...... proven to be an efficient way of obtaining multiple realizations that honor the same multiple-point statistics as the training image. The frequency matching method provides an alternative way of formulating multiple-point-based a priori models. In this strategy the pattern frequency distributions (i...... information in probabilistic inverse problems. Unfortunately, when this strategy is applied with the multiple-point-based simulation algorithm SNESIM the reproducibility of training image patterns is violated. In this study we suggest to combine sequential simulation with the frequency matching method...

  5. Clinical significance of reduced cerebral metabolism in multiple sclerosis. A combined PET and MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xiayan; Tanaka, Makoto; Kondo, Susumu; Okamoto, Koichi [Gunma Univ., Maebashi (Japan). School of Medicine; Hirai, Shunsaku

    1998-04-01

    Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease`s natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO{sub 2}). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman`s rank correlation coefficients. A general reduction in rCBF and rCMRO{sub 2} in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO{sub 2}. A correlation between the decrease in rCMRO{sub 2} and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information. (author)

  6. The multiplicative effect of combining alcohol with energy drinks on adolescent gambling.

    Science.gov (United States)

    Vieno, Alessio; Canale, Natale; Potente, Roberta; Scalese, Marco; Griffiths, Mark D; Molinaro, Sabrina

    2018-02-20

    There has been increased concern about the negative effects of adolescents consuming a combination of alcohol mixed with energy drinks (AmED). To date, few studies have focused on AmED use and gambling. The present study analyzed the multiplicative effect of AmED consumption, compared to alcohol alone, on the likelihood of at-risk or problem gambling during adolescence. Data from the ESPAD®Italia 2015 study, a cross-sectional survey conducted in a nationally representative sample of students (ages 15 to 19years) were used to examine the association between self-reported AmED use (≥6 times,≥10 times, and ≥20 times during the last month) and self-reported gambling severity. Multivariate models were used to calculate adjusted prevalence ratios to evaluate the association between alcohol use, AmED use, and gambling among a representative sample of adolescents who reported gambling in the last year and completed a gambling severity scale (n=4495). Among the 19% students classed as at-risk and problem gamblers, 43.9% were classed as AmED consumers, while 23.6% were classed as alcohol consumers (i.e. did not mix alcohol with energy drinks). In multivariate analyses that controlled for covariates, AmED consumers were three times more likely to be at-risk and problem gamblers (OR=3.05) compared to non-consuming adolescents, while the effect became less pronounced with considering those who consumed alcohol without the addition of energy drinks (OR=1.37). The present study clearly established that consuming AmED might pose a significantly greater risk of experiencing gambling-related problems among adolescents. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Improved Diagnostic Accuracy of Alzheimer's Disease by Combining Regional Cortical Thickness and Default Mode Network Functional Connectivity: Validated in the Alzheimer's Disease Neuroimaging Initiative Set.

    Science.gov (United States)

    Park, Ji Eun; Park, Bumwoo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai; Oh, Joo Young; Lee, Jae-Hong; Roh, Jee Hoon; Shim, Woo Hyun

    2017-01-01

    To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease.

  8. [Diagnostics in osteology].

    Science.gov (United States)

    Jakob, F; Genest, F; Seefried, L; Tsourdi, E; Lapa, C; Hofbauer, L C

    2016-07-01

    Clinical diagnostics in metabolic bone diseases cover a broad spectrum of conventional and state of the art methods ranging from the medical history and clinical examination to molecular imaging. Patient treatment is carried out in an interdisciplinary team due to the multiple interactions of bone with other organ systems. Diagnosis of osteoporosis is supported by high level national guidelines. A paradigm shift concerning the clinical relevance of bone mineral density measurement renders this now to be a strong risk factor rather than a diagnostic parameter, while strengthening the value of other clinical factors for risk assessment. The impact of parameters for muscle mass, structure and function is steadily increasing in all age groups. In order to identify underlying diseases that influence bone metabolism a panel of general laboratory diagnostic parameters is recommended. Markers for bone formation and resorption and specific parameters for the regulation of calcium and phosphate metabolism should be evaluated by specialists because they require diligence in preanalytics and experience in interpretation. Genetic diagnosis is well established for rare bone diseases while diagnostic panels are not yet available for routine diagnostics in polygenetic diseases such as osteoporosis. Conventional radiology is still very important to identify, e. g. fractures, osteolytic and osteoblastic lesions and extraosseous calcifications; however tomography-based methods which combine, e. g. scintigraphy or positron emission technologies with anatomical imaging are of increasing significance. Clinical diagnostics in osteology require profound knowledge and are subject to a dynamic evolution.

  9. Modeling Simultaneous Multiple Fracturing Using the Combined Finite-Discrete Element Method

    Directory of Open Access Journals (Sweden)

    Quansheng Liu

    2018-01-01

    Full Text Available Simultaneous multiple fracturing is a key technology to facilitate the production of shale oil/gas. When multiple hydraulic fractures propagate simultaneously, there is an interaction effect among these propagating hydraulic fractures, known as the stress-shadow effect, which has a significant impact on the fracture geometry. Understanding and controlling the propagation of simultaneous multiple hydraulic fractures and the interaction effects between multiple fractures are critical to optimizing oil/gas production. In this paper, the FDEM simulator and a fluid simulator are linked, named FDEM-Fluid, to handle hydromechanical-fracture coupling problems and investigate the simultaneous multiple hydraulic fracturing mechanism. The fractures propagation and the deformation of solid phase are solved by FDEM; meanwhile the fluid flow in the fractures is modeled using the principle of parallel-plate flow model. Several tests are carried out to validate the application of FDEM-Fluid in hydraulic fracturing simulation. Then, this FDEM-Fluid is used to investigate simultaneous multiple fractures treatment. Fractures repel each other when multiple fractures propagate from a single horizontal well, while the nearby fractures in different horizontal wells attract each other when multiple fractures propagate from multiple parallel horizontal wells. The in situ stress also has a significant impact on the fracture geometry.

  10. Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders

    NARCIS (Netherlands)

    van Pelt, E. Danielle; Neuteboom, Rinze F.; Ketelslegers, Immy A.; Boon, Maartje; Catsman-Berrevoets, Coriene E.; Hintzen, Rogier Q.

    Background Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. Objective To evaluate the

  11. In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI

    Science.gov (United States)

    2016-09-01

    cases with milder cortical disease. Evidence of meningeal inflam - mation in MS, however, is still debated. Future stud- ies combining our methods and...Bunyan RF, et al. Inflam - matory cortical demyelination in early multiple sclerosis. N Engl J Med 2011;365:2188–2197. 22. Magliozzi R, Howell O, Vora

  12. Combined thalidomide and cyclophosphamide treatment for refractory or relapsed multiple myeloma patients : a prospective phase II study

    NARCIS (Netherlands)

    Hovenga, S; Daenen, SMGJ; de Wolf, JTM; van Imhoff, GW; Kluin-Nelemans, HC; Sluiter, WJ; Vellenga, E

    refractory multiple myeloma ( MM) with a response rate of 30-40% at doses of 200-800 mg but with considerable side effects. We questioned whether lower doses of thalidomide in combination with a daily dose of cyclophosphamide might be an effective regimen with fewer side effects. We included 38

  13. A mathematical framework for combining decisions of multiple experts toward accurate and remote diagnosis of malaria using tele-microscopy.

    Directory of Open Access Journals (Sweden)

    Sam Mavandadi

    Full Text Available We propose a methodology for digitally fusing diagnostic decisions made by multiple medical experts in order to improve accuracy of diagnosis. Toward this goal, we report an experimental study involving nine experts, where each one was given more than 8,000 digital microscopic images of individual human red blood cells and asked to identify malaria infected cells. The results of this experiment reveal that even highly trained medical experts are not always self-consistent in their diagnostic decisions and that there exists a fair level of disagreement among experts, even for binary decisions (i.e., infected vs. uninfected. To tackle this general medical diagnosis problem, we propose a probabilistic algorithm to fuse the decisions made by trained medical experts to robustly achieve higher levels of accuracy when compared to individual experts making such decisions. By modelling the decisions of experts as a three component mixture model and solving for the underlying parameters using the Expectation Maximisation algorithm, we demonstrate the efficacy of our approach which significantly improves the overall diagnostic accuracy of malaria infected cells. Additionally, we present a mathematical framework for performing 'slide-level' diagnosis by using individual 'cell-level' diagnosis data, shedding more light on the statistical rules that should govern the routine practice in examination of e.g., thin blood smear samples. This framework could be generalized for various other tele-pathology needs, and can be used by trained experts within an efficient tele-medicine platform.

  14. A Review of the State-of-the-Art on Combining Multiple NDT Techniques in Terms of Precise Fault Detection

    Directory of Open Access Journals (Sweden)

    Ashish Khaira

    2017-06-01

    Full Text Available The present industrial scenario demands optimum quality, feasible processing time and enhanced machine availability to cope-up with continuously increasing customer expectations. To achieve this target, it is mandatory to ensure the optimum performance and higher availability of machinery. Therefore, the present work begins with, review of the research work of different researchers, which includes the applied combinations from year 2000-2016 proceed with discussion on the parameters being checked before making combination of NDT and finally, covers the maintenance performance parameters for quantifying improvement in performance after combining NDT. The result indicates that very few researches uses combination of NDT’s, in areas like aeronautical, compressors etc., and most of the works done in composites to be tested without using any decision making technique.  The researchers and practitioners can use the outcome of this work as a guideline for combining multiple NDT technique to achieve precise fault prediction and forecasting of upcoming failures.

  15. Interleukin 35 and Hepatocyte Growth Factor; as a novel combined immune gene therapy for Multiple Sclerosis disease.

    Science.gov (United States)

    Moghadam, Samira; Erfanmanesh, Maryam; Esmaeilzadeh, Abdolreza

    2017-11-01

    An autoimmune demyelination disease of the Central Nervous System, Multiple Sclerosis, is a chronic inflammation which mostly involves young adults. Suffering people face functional loss with a severe pain. Most current MS treatments are focused on the immune response suppression. Approved drugs suppress the inflammatory process, but factually, there is no definite cure for Multiple Sclerosis. Recently developed knowledge has demonstrated that gene and cell therapy as a hopeful approach in tissue regeneration. The authors propose a novel combined immune gene therapy for Multiple Sclerosis treatment using anti-inflammatory and remyelination of Interleukine-35 and Hepatocyte Growth Factor properties, respectively. In this hypothesis Interleukine-35 and Hepatocyte Growth Factor introduce to Mesenchymal Stem Cells of EAE mouse model via an adenovirus based vector. It is expected that Interleukine-35 and Hepatocyte Growth Factor genes expressed from MSCs could effectively perform in immunotherapy of Multiple Sclerosis. Copyright © 2017. Published by Elsevier Ltd.

  16. [Breast Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine Monotherapy after Failure of Combination Therapy Comprising Bevacizumab and Paclitaxel].

    Science.gov (United States)

    Ooe, Asako; Suganuma, Yasushi

    2016-03-01

    We report a case of breast cancer with multiple liver metastases successfully treated with capecitabine monotherapy after failure of combination therapy comprising bevacizumab (Bev) and paclitaxel (PTX). In March 2012, a 67-year-old woman was diagnosed with Stage IV breast cancer with massive pleural effusion. Histological examination showed invasive ductal carcinoma (scirrhous carcinoma) that was positive for hormonal receptor but negative for HER2 expression, and the nuclear grade was 1. She first received chemotherapy to decrease the tumor volume followed by hormonal therapy. After progression, imaging studies showed increased multiple lung and liver metastases and pleural effusion. Subsequently, treatment with combination of Bev and PTX was started from July 2014. After 4 courses of the combination therapy, multiple liver metastases were unchanged, but her liver function was impaired. Hence, she received capecitabine monotherapy (1,800 mg bis in die [BID]; 2-week administration followed by a week of rest). Her liver function improved early, and a partial response (PR) in the multiple liver metastases was achieved 3 months after initiation of therapy. Furthermore, the metastatic lesions were well controlled 4 months later. These findings suggest that the sensitivity to an anticancer agent greatly varies among patients.

  17. Assessing for Multiple Endocrine Neoplasia Type 1 in Patients Evaluated for Zollinger-Ellison Syndrome-Clues to a Safer Diagnostic Process.

    Science.gov (United States)

    Singh Ospina, Naykky; Donegan, Diane; Rodriguez-Gutierrez, Rene; Al-Hilli, Zahraa; Young, William F

    2017-05-01

    Zollinger-Ellison syndrome is a rare cause of tumoral hypergastrinemia; 1 of 5 patients with this syndrome also has multiple endocrine neoplasia type 1. The diagnosis of this disease is complicated by the widespread use of proton pump inhibitors that can elevate serum gastrin levels, the cornerstone for biochemical diagnosis. Abrupt discontinuation of proton pump inhibitors could lead to adverse outcomes. Clinician awareness of the relationship between Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1 could lead to a safer diagnostic pathway. We conducted a retrospective review of a cohort of patients with multiple endocrine neoplasia type 1. There were 287 patients with multiple endocrine neoplasia type 1 (73 with gastrinoma) evaluated between 1997 and 2014. Two patients experienced adverse events after proton pump inhibitor therapy was discontinued to re-measure serum gastrin level during the evaluation of severe peptic ulcer disease. In both cases, the diagnosis of multiple endocrine neoplasia type 1 was made after proton pump therapy was discontinued. Abrupt discontinuation of proton pump therapy can lead to adverse outcomes in patients with Zollinger-Ellison syndrome. Clinical assessment for features of multiple endocrine neoplasia type 1 (eg, serum calcium levels, personal and family history of hypercalcemia, pituitary or pancreatic tumors) could identify patients with higher risk for a tumoral source of hypergastrinemia where imaging studies can help support the diagnosis without the potential side effects of abrupt discontinuation of proton pump inhibitor therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Lesion type and reader experience affect the diagnostic accuracy of breast MRI: A multiple reader ROC study

    Energy Technology Data Exchange (ETDEWEB)

    Baltzer, Pascal A.T., E-mail: patbaltzer@gmail.com [Department of Biomedical Imaging and Imge-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna (Austria); Kaiser, Werner Alois [Department of Diagnostic and Interventional Radiology, University Hospital Jena, Erlanger Allee 101, 07740 Jena (Germany); Dietzel, Matthias, E-mail: dietzelmatthias2@hotmail.com [Department of Neuroradiology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen (Germany)

    2015-01-15

    Highlights: • The main findings of our study are, that reader experience and lesion type (i.e., mass versus non-mass enhancement) are independent predictors of the diagnostic accuracy of breast MRI. • Specifically, benign and malignant non-mass lesions cannot be differentiated with sufficient accuracy, especially if readers are not experienced. • We conclude that future research in breast MRI should focus on non-mass lesions, as these are the problem makers in modern breast MRI. - Abstract: Purpose: To evaluate the influence of lesion type (mass versus non-mass) and reader experience on the diagnostic performance of breast MRI (BMRI) in a non-screening setting. Materials and methods: Consecutive patients (mean age, 55 ± 12 years) with breast lesions that were verified by biopsy or surgery, and who had had BMRI as part of their diagnostic workup, were eligible for this retrospective single-center study. Cancers diagnosed by biopsy before BMRI were excluded to eliminate biological and interpretation bias due to biopsy or chemotherapy effects (n = 103). Six blinded readers (experience level, high (HE, n = 2); intermediate (IE, n = 2); and low (LE, n = 2)) evaluated all examinations and assigned independent MRI BI-RADS ratings. Lesion type (mass, non-mass, focal) was noted. Receiver operating characteristics (ROC) and logistic regression analysis was performed to compare diagnostic accuracies. Results: There were 259 histologically verified lesions (123 malignant, 136 benign) investigated. There were 169 mass (103 malignant, 66 benign) and 48 non-mass lesions (19 malignant, 29 benign). Another 42 lesions that met the inclusion criteria were biopsied due to conventional findings (i.e., microcalcifications, architectural distortions), but did not enhance on MRI (41 benign, one DCIS). ROC analysis revealed a total area under the curve (AUC) between 0.834 (LE) and 0.935 (HI). Logistic regression identified a significant effect of non-mass lesions (P < 0.0001) and

  19. Intestinal resection and multiple abdominal hernia mesh repair: is the combination safe and feasible?

    Science.gov (United States)

    Campanelli, Giampiero; Nicolosi, Filadelfio Massimiliano; Pettinari, Diego; Avesani, Ettore Contessini

    2004-01-01

    In a highly advanced era from the point of view of instrumental diagnostic resolution it is, however, not always possible to obtain a precise preoperative diagnosis. Surgery is sometimes the only decisive solution. In April 2003, a 62-year-old male patient was referred to us for umbilical hernia, diastasis recti abdominis and left-sided inguinal hernia; he also complained of pain in the mesogastric-hypogastric region. This site presented with a hard, non-mobile, painful tumefaction at both superficial and deep palpation. The patient was submitted to various diagnostic examinations (pancolonoscopy, CT, X-ray of the digestive tract and angiography), but only surgery allowed us to establish the specific nature of the tumefaction. The operation consisted in the en-bloc removal of an abscess mass affecting intestinal loops, caecum and appendix and at the same time in the repair of the hernia components with the use of prosthesis in a potentially contaminated area. The tumefaction had originated following acute appendicitis episodes that had determined adherences between the appendix, caecum and ileal loops (histologically confirmed). There are situations that require surgery in order to be explicitly diagnosed and solved. Furthermore, although the use of prosthetic materials in the treatment of hernias in association with intestinal resection is an extreme case, it has also been reported in the international literature that nowadays there are no real contraindications to the implantation of a prosthesis in a potentially infected area.

  20. Diagnostic performance of combined noninvasive coronary angiography and myocardial perfusion imaging using 320 row detector computed tomography

    DEFF Research Database (Denmark)

    Vavere, Andrea L; Simon, Gregory G; George, Richard T

    2013-01-01

    Multidetector coronary computed tomography angiography (CTA) is a promising modality for widespread clinical application because of its noninvasive nature and high diagnostic accuracy as found in previous studies using 64 to 320 simultaneous detector rows. It is, however, limited in its ability t...

  1. Clinical validation of the international consensus diagnostic criteria and algorithms for autoimmune pancreatitis: combined IAP and KPBA meeting 2013 report.

    Science.gov (United States)

    Song, Tae Jun; Kim, Myung-Hwan; Kim, Min Jae; Moon, Sung Hoon; Han, Ji Min

    2014-01-01

    There have been great developments in the diagnosis and treatment of autoimmune pancreatitis (AIP) in the last decade. Most significantly, the international consensus diagnostic criteria (ICDC) proposed in 2011 were the first attempt to provide unified diagnostic criteria incorporating most features of the previously existing national criteria. However, the ICDC have not yet been prospectively validated using evidence-based studies since their introduction. An international symposium on the diagnosis of AIP was held in Seoul, South Korea on September 6, 2013, in cooperation with the International Association of Pancreatology and the Korean Pancreatobiliary Association meeting. In contrast to other symposia in the past, which had primarily focused on the diagnostic criteria themselves, expert panels in this symposium discussed how the diagnostic criteria and algorithms had been embraced in clinical settings to diagnose AIP in each country and conducted a comprehensive evaluation of these criteria and algorithms. It was acknowledged that there was a room for improvement in the ICDC and their algorithms and that further modifications might be required in the future. Prospective clinical validation in larger series is needed for confirmation. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  2. Combined Dynamic Time Warping with Multiple Sensors for 3D Gesture Recognition

    National Research Council Canada - National Science Library

    Hyo-Rim Choi; TaeYong Kim

    2017-01-01

    .... Several studies have been undertaken in the field of gesture recognition; however, gesture recognition was conducted based on data captured from various independent sensors, which rendered the capture and combination of real-time data complicated...

  3. On Combining Multiple-Instance Learning and Active Learning for Computer-Aided Detection of Tuberculosis

    NARCIS (Netherlands)

    Melendez Rodriguez, J.C.; Ginneken, B. van; Maduskar, P.; Philipsen, R.H.H.M.; Ayles, H.; Sanchez, C.I.

    2016-01-01

    The major advantage of multiple-instance learning (MIL) applied to a computer-aided detection (CAD) system is that it allows optimizing the latter with case-level labels instead of accurate lesion outlines as traditionally required for a supervised approach. As shown in previous work, a MIL-based

  4. Combining multiple serum tumor markers improves detection of stage I epithelial ovarian cancer

    NARCIS (Netherlands)

    Zhang, Zhen; Yu, Yinhua; Xu, Fengji; Berchuck, Andrew; van Haaften-Day, Carolien; Havrilesky, Laura J.; de Bruijn, Henk W. A.; van der Zee, Ate G. J.; Woolas, Robert P.; Jacobs, Ian J.; Skates, Steven; Chan, Daniel W.; Bast, Robert C.

    2007-01-01

    Objective. Currently available tumor markers for ovarian cancer are still inadequate in both sensitivity and specificity to be used for population-based screening. Artificial neural network (ANN) as a modeling tool has demonstrated its ability to assimilate information from multiple sources and to

  5. Combined Statistical Analyses for Long-Term Stability Data with Multiple Storage Conditions : A Simulation Study

    NARCIS (Netherlands)

    Almalik, Osama; Nijhuis, Michiel B.; van den Heuvel, Edwin R.

    2014-01-01

    Shelf-life estimation usually requires that at least three registration batches are tested for stability at multiple storage conditions. The shelf-life estimates are often obtained by linear regression analysis per storage condition, an approach implicitly suggested by ICH guideline Q1E. A linear

  6. Tracking Iron in Multiple Sclerosis: A Combined Imaging and Histopathological Study at 7 Tesla

    Science.gov (United States)

    Bagnato, Francesca; Hametner, Simon; Yao, Bing; van Gelderen, Peter; Merkle, Hellmut; Cantor, Fredric K.; Lassmann, Hans; Duyn, Jeff H.

    2011-01-01

    Previous authors have shown that the transverse relaxivity R[subscript 2][superscript *] and frequency shifts that characterize gradient echo signal decay in magnetic resonance imaging are closely associated with the distribution of iron and myelin in the brain's white matter. In multiple sclerosis, iron accumulation in brain tissue may reflect a…

  7. Multiple resistance of horseweed to glyphosate and paraquat and its control with paraquat and metribuzin combinations

    Science.gov (United States)

    Greenhouse and field studies were conducted in 2007 and 2008 to investigate possible multiple-resistance of horseweed to paraquat and glyphosate, and to evaluate the effect of the addition of metribuzin to paraquat on control of paraquat-resistant horseweed. Results indicated that the GR50 (herbicid...

  8. Diagnostic Performance of Alpha-Fetoprotein, Protein Induced by Vitamin K Absence, Osteopontin, Dickkopf-1 and Its Combinations for Hepatocellular Carcinoma

    Science.gov (United States)

    Jang, Eun Sun; Jeong, Sook-Hyang; Kim, Jin-Wook; Choi, Yun Suk; Leissner, Philippe; Brechot, Christian

    2016-01-01

    Background & Aims Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. As complementary biomarkers, protein induced by vitamin K absence (PIVKA-II), osteopontin (OPN), and Dickkopf-1 (DKK-1) have been proposed. This study aimed to perform a head-to-head comparison of the diagnostic performance of AFP, PIVKA-II, OPN and DKK-1 as single or in combination to seek the best biomarker or panel, and to investigate the clinical factors affecting their performance. Methods Using 401 stored plasma samples obtained from 208 HCC patients and 193 liver cirrhosis control patients, plasma AFP, PIVKA-II, OPN and DKK-1 levels were measured by ELISA, and receiver operating characteristic curve analyses were performed for each biomarker and for every combination of two to four markers. Results Of the four biomarkers, AFP showed the highest area under the curve (0.786). The sensitivity and specificity for each single biomarker was 62% and 90.2% (AFP>20 ng/mL), 51.0% and 91.2% (PIVKA-II>10 ng/mL), 46.2% and 80.3% (OPN>100 ng/mL), and 50.0% and 80.8% (DKK-1>500 pg/mL), respectively. Among the combinations of two biomarkers, AFP>20 ng/mL or DKK-1>500 pg/mL showed the best diagnostic performance (sensitivity 78.4%, specificity 72.5%). Triple or quadruple combination did not improve the diagnostic performance further. The patient’s age, etiology and tumor invasiveness of HCC affected the performance of each marker. Conclusions AFP was the most useful single biomarker for HCC diagnosis, and the combined measurement of AFP and DKK-1 could maximize the diagnostic yield. Clinical decision should be based on the consideration of various factors affecting the diagnostic performance of each biomarker. Efforts to seek novel HCC biomarkers should be continued. PMID:26986465

  9. In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI

    Science.gov (United States)

    2015-09-01

    structural tissue changes in the cortex of patients with relapsing-remitting (RR) MS by combining advanced MR studies at 7 T MRI , to measure cortical...MACFIMS. Multilinear regression models were used to compare MS SUVR vs HC SUVR in different brain tissue compartments (cortex, cortical lesions, WM...channel coil to acquire a structural scan with a 3D magnetiza- tion-prepared rapid acquisition with multiple gradient echoes (MEMPR) [repetition time

  10. Shared and unique responses of plants to multiple individual stresses and stress combinations: physiological and molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Prachi ePandey

    2015-09-01

    Full Text Available In field conditions, plants are often simultaneously exposed to multiple biotic and abiotic stresses resulting in substantial yield loss. Plants have evolved various physiological and molecular adaptations to protect themselves under stress combinations. Emerging evidences suggest that plant responses to a combination of stresses are unique from individual stress responses. In addition, plants exhibit shared responses which are common to individual stresses and stress combination. In this review, we provide an update on the current understanding of both unique and shared responses. Specific focus of this review is on heat-drought stress as a major abiotic stress combination and, drought-pathogen and heat-pathogen as examples of abiotic-biotic stress combinations. We also comprehend the current understanding of molecular mechanisms of cross talk in relation to shared and unique molecular responses for plant survival under stress combinations. Thus, the knowledge of shared responses of plants from individual stress studies and stress combinations can be utilized to develop varieties with broad spectrum stress tolerance.

  11. Shared and unique responses of plants to multiple individual stresses and stress combinations: physiological and molecular mechanisms.

    Science.gov (United States)

    Pandey, Prachi; Ramegowda, Venkategowda; Senthil-Kumar, Muthappa

    2015-01-01

    In field conditions, plants are often simultaneously exposed to multiple biotic and abiotic stresses resulting in substantial yield loss. Plants have evolved various physiological and molecular adaptations to protect themselves under stress combinations. Emerging evidences suggest that plant responses to a combination of stresses are unique from individual stress responses. In addition, plants exhibit shared responses which are common to individual stresses and stress combination. In this review, we provide an update on the current understanding of both unique and shared responses. Specific focus of this review is on heat-drought stress as a major abiotic stress combination and, drought-pathogen and heat-pathogen as examples of abiotic-biotic stress combinations. We also comprehend the current understanding of molecular mechanisms of cross talk in relation to shared and unique molecular responses for plant survival under stress combinations. Thus, the knowledge of shared responses of plants from individual stress studies and stress combinations can be utilized to develop varieties with broad spectrum stress tolerance.

  12. Combining multiple hypothesis testing and affinity propagation clustering leads to accurate, robust and sample size independent classification on gene expression data

    Directory of Open Access Journals (Sweden)

    Sakellariou Argiris

    2012-10-01

    Full Text Available Abstract Background A feature selection method in microarray gene expression data should be independent of platform, disease and dataset size. Our hypothesis is that among the statistically significant ranked genes in a gene list, there should be clusters of genes that share similar biological functions related to the investigated disease. Thus, instead of keeping N top ranked genes, it would be more appropriate to define and keep a number of gene cluster exemplars. Results We propose a hybrid FS method (mAP-KL, which combines multiple hypothesis testing and affinity propagation (AP-clustering algorithm along with the Krzanowski & Lai cluster quality index, to select a small yet informative subset of genes. We applied mAP-KL on real microarray data, as well as on simulated data, and compared its performance against 13 other feature selection approaches. Across a variety of diseases and number of samples, mAP-KL presents competitive classification results, particularly in neuromuscular diseases, where its overall AUC score was 0.91. Furthermore, mAP-KL generates concise yet biologically relevant and informative N-gene expression signatures, which can serve as a valuable tool for diagnostic and prognostic purposes, as well as a source of potential disease biomarkers in a broad range of diseases. Conclusions mAP-KL is a data-driven and classifier-independent hybrid feature selection method, which applies to any disease classification problem based on microarray data, regardless of the available samples. Combining multiple hypothesis testing and AP leads to subsets of genes, which classify unknown samples from both, small and large patient cohorts with high accuracy.

  13. Combining MCDA and risk analysis: dealing with scaling issues in the multiplicative AHP

    DEFF Research Database (Denmark)

    Barfod, Michael Bruhn; van den Honert, Rob; Salling, Kim Bang

    This paper proposes a new decision support system (DSS) for applying risk analysis and stochastic simulation to the multiplicative AHP in order to deal with issues concerning the progression factors. The multiplicative AHP makes use of direct rating on a logarithmic scale, and for this purpose...... the progression factor 2 is used for calculating scores of alternatives and √2 for calculation of criteria weights when transforming the verbal judgments stemming from pair wise comparisons. However, depending on the decision context, the decision-makers aversion towards risk, etc., it is most likely...... that the decision-makers have varying progression factors in their perception of the scales. This potential variability in progression factors implies a form of uncertainty in the DSS which can be modelled by stochastic simulation. With reference to previous work, which proposes to conduct sensitivity analysis...

  14. A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology

    Science.gov (United States)

    Kolasinski, James; Chance, Steven A.; DeLuca, Gabriele C.; Esiri, Margaret M.; Chang, Eun-Hyuk; Palace, Jacqueline A.; McNab, Jennifer A.; Jenkinson, Mark; Miller, Karla L.; Johansen-Berg, Heidi

    2012-01-01

    Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional

  15. Multiple Criteria Decision Making Combined with VRP: A Categorized Bibliographic Study

    OpenAIRE

    Yahia Zare Mehrjerdi

    2015-01-01

    In this research author reviews references related to the topic of multi criterion (goal programming, multiple objective linear and nonlinear programming, bi-criterion programming, Multi Attribute Decision Making, Compromise Programming, Surrogate Worth Trade-off Method) and various versions of vehicle routing problem (VRP), Multi depot VRP (MDVRP), VRP with time windows (VRPWTW), Stochastic VRP (SVRP), Capacitated VRP (CVRP), Fuzzy VRP (FVRP), Location VRP (LVRP), Backhauling VRP(BHVRP), Fac...

  16. Combining Multiple External Representations and Refutational Text: An Intervention on Learning to Interpret Box Plots

    Science.gov (United States)

    Lem, Stephanie; Kempen, Goya; Ceulemans, Eva; Onghena, Patrick; Verschaffel, Lieven; Van Dooren, Wim

    2015-01-01

    Box plots are frequently misinterpreted and educational attempts to correct these misinterpretations have not been successful. In this study, we used two instructional techniques that seemed powerful to change the misinterpretation of the area of the box in box plots, both separately and in combination, leading to three experimental conditions,…

  17. Combining qualitative and quantitative operational research methods to inform quality improvement in pathways that span multiple settings.

    Science.gov (United States)

    Crowe, Sonya; Brown, Katherine; Tregay, Jenifer; Wray, Jo; Knowles, Rachel; Ridout, Deborah A; Bull, Catherine; Utley, Martin

    2017-08-01

    Improving integration and continuity of care across sectors within resource constraints is a priority in many health systems. Qualitative operational research methods of problem structuring have been used to address quality improvement in services involving multiple sectors but not in combination with quantitative operational research methods that enable targeting of interventions according to patient risk. We aimed to combine these methods to augment and inform an improvement initiative concerning infants with congenital heart disease (CHD) whose complex care pathway spans multiple sectors. Soft systems methodology was used to consider systematically changes to services from the perspectives of community, primary, secondary and tertiary care professionals and a patient group, incorporating relevant evidence. Classification and regression tree (CART) analysis of national audit datasets was conducted along with data visualisation designed to inform service improvement within the context of limited resources. A 'Rich Picture' was developed capturing the main features of services for infants with CHD pertinent to service improvement. This was used, along with a graphical summary of the CART analysis, to guide discussions about targeting interventions at specific patient risk groups. Agreement was reached across representatives of relevant health professions and patients on a coherent set of targeted recommendations for quality improvement. These fed into national decisions about service provision and commissioning. When tackling complex problems in service provision across multiple settings, it is important to acknowledge and work with multiple perspectives systematically and to consider targeting service improvements in response to confined resources. Our research demonstrates that applying a combination of qualitative and quantitative operational research methods is one approach to doing so that warrants further consideration. Published by the BMJ Publishing Group

  18. Multiple coronary arteriovenous fistulae combined with ventricular septal defect: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Kun Sik; Zeon, Seok Kil; Kim, Ki Sik [Keimyung University, School of Medicine, Daegu (Korea, Republic of); Oh, Yeon Hee [Pohang Hospital, Dongguk University, Pohang (Korea, Republic of)

    1992-01-15

    Congenital coronary arteriovenous fistulas are all of those anomalies and malformations that result in a direct communication of a coronary artery and/or any of its branches with a cardiac chamber or extra cardiac vessel resulting in a shunt of varying proportions. The majority of these fistulas form an A-V connection between a coronary artery and the right heart chambers, and rarely their is communication with the left heart chambers. In most reported cases, the abnormal fistula involves only one coronary artery which developed alone. This report describes a unique case in which multiple coronary fistulas associated with VSD were encountered.

  19. Ancestral state reconstruction reveals multiple independent evolution of diagnostic morphological characters in the "Higher Oribatida" (Acari), conflicting with current classification schemes

    Science.gov (United States)

    2010-01-01

    Background The use of molecular genetic data in phylogenetic systematics has revolutionized this field of research in that several taxonomic groupings defined by traditional taxonomic approaches have been rejected by molecular data. The taxonomic classification of the oribatid mite group Circumdehiscentiae ("Higher Oribatida") is largely based on morphological characters and several different classification schemes, all based upon the validity of diagnostic morphological characters, have been proposed by various authors. The aims of this study were to test the appropriateness of the current taxonomic classification schemes for the Circumdehiscentiae and to trace the evolution of the main diagnostic traits (the four nymphal traits scalps, centrodorsal setae, sclerits and wrinkled cuticle plus octotaxic system and pteromorphs both in adults) on the basis of a molecular phylogenetic hypothesis by means of parsimony, likelihood and Bayesian approaches. Results The molecular phylogeny based on three nuclear markers (28S rDNA, ef-1α, hsp82) revealed considerable discrepancies to the traditional classification of the five "circumdehiscent" subdivisions, suggesting paraphyly of the three families Scutoverticidae, Ameronothridae, Cymbaeremaeidae and also of the genus Achipteria. Ancestral state reconstructions of six common diagnostic characters and statistical evaluation of alternative phylogenetic hypotheses also partially rejected the current morphology-based classification and suggested multiple convergent evolution (both gain and loss) of some traits, after a period of rapid cladogenesis, rendering several subgroups paraphyletic. Conclusions Phylogenetic studies revealed non-monophyly of three families and one genus as a result of a lack of adequate synapomorphic morphological characters, calling for further detailed investigations in a framework of integrative taxonomy. Character histories of six morphological traits indicate that their evolution followed a rather

  20. Ensemble approach combining multiple methods improves human transcription start site prediction

    LENUS (Irish Health Repository)

    Dineen, David G

    2010-11-30

    Abstract Background The computational prediction of transcription start sites is an important unsolved problem. Some recent progress has been made, but many promoters, particularly those not associated with CpG islands, are still difficult to locate using current methods. These methods use different features and training sets, along with a variety of machine learning techniques and result in different prediction sets. Results We demonstrate the heterogeneity of current prediction sets, and take advantage of this heterogeneity to construct a two-level classifier (\\'Profisi Ensemble\\') using predictions from 7 programs, along with 2 other data sources. Support vector machines using \\'full\\' and \\'reduced\\' data sets are combined in an either\\/or approach. We achieve a 14% increase in performance over the current state-of-the-art, as benchmarked by a third-party tool. Conclusions Supervised learning methods are a useful way to combine predictions from diverse sources.

  1. ExtMiner: Combining multiple ranking and clustering algorithms for structured document retrieval

    OpenAIRE

    Nurminen, Miika; Honkaranta, Anne; Kärkkäinen, Tommi

    2005-01-01

    This paper introduces ExtMiner, a platform and potential tool for information management in SMEs (small & medium-size enterprise), or for organizational workgroups. ExtMiner supports interactive and iterative clustering of documents. It provides users with a visual cluster and list views at the same time, supporting iterative search process. ExtMiner may also be applied as a platform for research on retrieval fusion, since it combines search, clustering and visualization algorithms. ExtMiner ...

  2. The Effect of Multiple Sulfatase Deficiency (MSD) on Dental Development: Can We Use the Teeth as an Early Diagnostic Tool?

    OpenAIRE

    Zilberman, Uri; Bibi, Haim

    2016-01-01

    Background: Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of metabolism due to reduced catalytic activity of the different sulfatase. Affected individuals show neurologic deterioration with mental retardation, skeletal anomalies, organomegaly, and skin changes as in X-linked ichthyosis. The only organ that was not examined in MSD patients is the dentition.

  3. Multiple Criteria Decision Making Combined with VRP: A Categorized Bibliographic Study

    Directory of Open Access Journals (Sweden)

    Yahia Zare Mehrjerdi

    2015-08-01

    Full Text Available In this research author reviews references related to the topic of multi criterion (goal programming, multiple objective linear and nonlinear programming, bi-criterion programming, Multi Attribute Decision Making, Compromise Programming, Surrogate Worth Trade-off Method and various versions of vehicle routing problem (VRP, Multi depot VRP (MDVRP, VRP with time windows (VRPWTW, Stochastic VRP (SVRP, Capacitated VRP (CVRP, Fuzzy VRP (FVRP, Location VRP (LVRP, Backhauling VRP(BHVRP, Facility Location VRP (FLVRP, and Inventory control VRP (ICVRP. Although, VRP is a research area with rich research works and powerful researchers there found only 81 articles that relates various vehicle routing type problems with various multiple objectives techniques. This author found that there is no research done in some areas of VRP (i.e., FVRP, ICVRP, LRP and CVRP. It is interesting to see that this research area was completely an unattractive to master students (with zero research reported and a somewhat attractive area to doctoral students (with 6 researches reported. Among the many multi criterion programming techniques available only three of them (goal programming, bi-criterion programming, linear and nonlinear multi objective programming are being employed to solve the problem.

  4. Imputation and quality control steps for combining multiple genome-wide datasets

    Directory of Open Access Journals (Sweden)

    Shefali S Verma

    2014-12-01

    Full Text Available The electronic MEdical Records and GEnomics (eMERGE network brings together DNA biobanks linked to electronic health records (EHRs from multiple institutions. Approximately 52,000 DNA samples from distinct individuals have been genotyped using genome-wide SNP arrays across the nine sites of the network. The eMERGE Coordinating Center and the Genomics Workgroup developed a pipeline to impute and merge genomic data across the different SNP arrays to maximize sample size and power to detect associations with a variety of clinical endpoints. The 1000 Genomes cosmopolitan reference panel was used for imputation. Imputation results were evaluated using the following metrics: accuracy of imputation, allelic R2 (estimated correlation between the imputed and true genotypes, and the relationship between allelic R2 and minor allele frequency. Computation time and memory resources required by two different software packages (BEAGLE and IMPUTE2 were also evaluated. A number of challenges were encountered due to the complexity of using two different imputation software packages, multiple ancestral populations, and many different genotyping platforms. We present lessons learned and describe the pipeline implemented here to impute and merge genomic data sets. The eMERGE imputed dataset will serve as a valuable resource for discovery, leveraging the clinical data that can be mined from the EHR.

  5. Multiple Resistance of Horseweed to Glyphosate and Paraquat and Its Control with Paraquat and Metribuzin Combinations

    Directory of Open Access Journals (Sweden)

    Daniel H. Poston

    2012-12-01

    Full Text Available Greenhouse and field studies were conducted in 2007 and 2008 to investigate possible multiple-resistance of horseweed to paraquat and glyphosate, and to evaluate the effect of the addition of metribuzin to paraquat on control of paraquat-resistant horseweed. Results indicated that the GR50 (herbicide dose required to cause a 50% reduction in plant growth value for the susceptible population S102 was 0.066 kg ae/ha glyphosate, and for the resistant population MDOT was 0.78 kg/ha glyphosate. The level of glyphosate resistance for MDOT was 12-fold compared with S102. The GR50 value for the susceptible population S102 was 0.078 kg ai/ha paraquat, and for the resistant population MDOT was 0.67 kg/ha paraquat. The level of paraquat resistance for MDOT was 9-fold compared to S102, suggesting multiple-resistance to glyphosate and paraquat in the MDOT population. In field studies the addition of metribuzin to paraquat improved horseweed control.

  6. [Sleep disturbances - an important factor in combination 'minor' symptoms of multiple sclerosis].

    Science.gov (United States)

    Yakupov, E Z; Troshina, Yu V

    2017-01-01

    To investigate the clinical and neurophysiological features of sleep disorders in patients with different forms of multiple sclerosis (MS) and their impact on life quality, dynamic and prognosis of the disease. Identify the impact of sleep disorders on the formation and maintenance of chronic fatigue syndrome in patients with MS. General clinical methods of examination like neuropsychological testing (definition of anxiety and depression), the scales of the subjective determination of the quality of sleep, the severity of daytime sleepiness, quality of life, severity of chronic fatigue syndrome) and their subsequent correlation with neuroimaging and neurophysiological data were studied. 54 patients with different forms of MS and 54 healthy volunteers in the control group were selected. Data analysis showed a high level of sleep disorders associated with anxiety disorders, comorbid pathologies, which is significantly higher in the study group.

  7. Combining Multiple Electrode Arrays for Two-Dimensional Electrical Resistivity Imaging Using the Unsupervised Classification Technique

    Science.gov (United States)

    Ishola, K. S.; Nawawi, M. N. M.; Abdullah, K.

    2015-06-01

    This article describes the use of k-means clustering, an unsupervised image classification technique, to help interpret subsurface targets. The k-means algorithm is employed to combine and classify the two-dimensional (2D) inverse resistivity models obtained from three different electrode arrays. The algorithm is initialized through the selection of the number of clusters, number of iterations and other parameters such as stopping criteria. Automatically, it seeks to find groups of closely related resistivity values that belong to the same cluster and are more similar to each other than resistivity values belonging to other clusters. The approach is applied to both synthetic and field data. The 2D postinversions of the resistivity data were preprocessed by resampling and interpolating to the same coordinate. Following the preprocessing, the three images are combined into a single classified image. All the image preprocessing, manipulation and analysis are performed using the PCI Geomatics software package. The results of the clustering and classification are presented as classified images. An assessment of the performance of the individual and combined images for the synthetic models is carried out using an error matrix, mean absolute error and mean absolute percent error. The estimated errors show that images obtained from maximum values of the reconstructed resistivity for the different models give the best representation of the true models. Additionally, the overall accuracy and kappa values show good agreement between the combined classified images and true models. Depending on the model, the overall accuracy ranges from 86 to 99 %, while the kappa coefficient is in the range of 54-98 %. Classified images with kappa coefficients greater than 0.8 show strong agreement, while images with kappa coefficients greater than 0.5 but less than 0.8 give moderate agreement. For the field data, the k-mean classifier produces images that incorporate structural features of

  8. Effect of combining multiple micronutrients with iron supplementation on Hb response in children: systematic review of randomized controlled trials.

    Science.gov (United States)

    Gera, Tarun; Sachdev, Harsh Pal Singh; Nestel, Penelope

    2009-06-01

    To study the effect of combining multiple (two or more) micronutrients with Fe supplementation on Hb response, when compared with placebo and with Fe supplementation, in children. Electronic databases, personal files, hand search of reviews, bibliographies of books, and abstracts and proceedings of international conferences. Randomized controlled trials evaluating change in Hb levels with interventions that included Fe and multiple-micronutrient supplementation in comparison to placebo alone or Fe alone were analysed in two systematic reviews. Twenty-five trials were included in the review comparing Fe and micronutrient supplementation with placebo. The pooled estimate (random effects model) for change in Hb with Fe and micronutrient supplementation (weighted mean difference) was 0.65 g/dl (95 % CI 0.50, 0.80, P micronutrients' and malarial non-hyperendemic region were significant predictors of greater Hb response and heterogeneity. Thirteen trials were included in the review comparing Fe and micronutrient supplementation with Fe alone. The pooled estimate for change in Hb with Fe and micronutrient supplementation (weighted mean difference) was 0.14 g/dl (95 % CI 0.00, 0.28, P = 0.04). None of the variables were found to be significant predictors of Hb response. Synthesized evidence indicates that addition of multiple micronutrients to Fe supplementation may only marginally improve Hb response compared with Fe supplementation alone. However, addition of 'other micronutrients' may have a negative effect. Routine addition of unselected multiple micronutrients to Fe therefore appears unjustified for nutritional anaemia control programmes.

  9. Security and reliability analysis of diversity combining techniques in SIMO mixed RF/FSO with multiple users

    KAUST Repository

    Abd El-Malek, Ahmed H.

    2016-07-26

    In this paper, we investigate the impact of different diversity combining techniques on the security and reliability analysis of a single-input-multiple-output (SIMO) mixed radio frequency (RF)/free space optical (FSO) relay network with opportunistic multiuser scheduling. In this model, the user of the best channel among multiple users communicates with a multiple antennas relay node over an RF link, and then, the relay node employs amplify-and-forward (AF) protocol in retransmitting the user data to the destination over an FSO link. Moreover, the authorized transmission is assumed to be attacked by a single passive RF eavesdropper equipped with multiple antennas. Therefore, the system security reliability trade-off analysis is investigated. Closed-form expressions for the system outage probability and the system intercept probability are derived. Then, the newly derived expressions are simplified to their asymptotic formulas at the high signal-to-noise- ratio (SNR) region. Numerical results are presented to validate the achieved exact and asymptotic results and to illustrate the impact of various system parameters on the system performance. © 2016 IEEE.

  10. Multiple-band light absorber via combining the fundamental mode and multiple splitting modes of the 3-order response of metamaterial resonator

    Science.gov (United States)

    Wang, Ben-Xin; Xie, Qin; Dong, Guangxi; Huang, Wei-Qing

    2017-12-01

    We present a rather simple metamaterial design consisted of only a rectangle-shape patch structure with a very small air strip on it to realize triple-band absorption at terahertz frequency. Results prove that three narrow-band absorption peaks are obtained at frequencies of 0.94 THz, 2.44 THz, and 2.85 THz, and the average absorption rates of the three peaks are 97.00%. The resonance at 0.94 THz is attributed to the fundamental mode (or 1-order) response of the metamaterial, while the last two modes are due to the two splitting modes of the 3-order response. The parameter changes of the small air strip in the rectangle-shape patch structure have large influence on the absorption performance of the metamaterial, in particular of the last two modes. Importantly, quad-band absorption can be obtained by introducing one more air strip in the rectangle-shape patch structure. It is found that the first resonance peak is derived from the 1-order response, whereas the last three modes stem from the three splitting modes of the 3-order response of the metamaterial. The combination of the 1-order resonance and multiple splitting modes of the 3-order response provides new design method to realize multiple-band light absorbers.

  11. Experimental study of resolution of proton chemical shifts in solids: Combined multiple pulse NMR and magic-angle spinning

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, L.M.; Taylor, R.E.; Paff, A.J.; Gerstein, B.C.

    1980-01-01

    High-resolution nuclear magnetic resonance spectra of protons in rigid, randomly oriented solids have been measured using combined homonuclear dipolar decoupling (via multiple pulse techniques) and attenuation of chemical shift anisotropies (via magic-angle sample spinning). Under those conditions, isotropic proton chemical shifts were recorded for a variety of chemical species, with individual linewidths varying from about 55 to 110 Hz (1--2 ppm). Residual line broadening was due predominately to (i) magnetic-field instability and inhomogeneity, (ii) unresolved proton--proton spin couplings, (iii) chemical shift dispersion, (iv) residual dipolar broadening, and (v) lifetime broadening under the multiple pulse sequences used. The magnitudes of those effects and the current limits of resolution for this experiment in our spectrometer have been investigated. The compounds studied included organic solids (4, 4'-dimethylbenzophenone, 2, 6-dimethylbenzoic acid, and aspirin), polymers (polystyrene and polymethylmethacrylate), and the vitrain portion of a bituminous coal.

  12. Combining multiple earthquake models in real time for earthquake early warning

    Science.gov (United States)

    Minson, Sarah E.; Wu, Stephen; Beck, James L; Heaton, Thomas H.

    2017-01-01

    The ultimate goal of earthquake early warning (EEW) is to provide local shaking information to users before the strong shaking from an earthquake reaches their location. This is accomplished by operating one or more real‐time analyses that attempt to predict shaking intensity, often by estimating the earthquake’s location and magnitude and then predicting the ground motion from that point source. Other EEW algorithms use finite rupture models or may directly estimate ground motion without first solving for an earthquake source. EEW performance could be improved if the information from these diverse and independent prediction models could be combined into one unified, ground‐motion prediction. In this article, we set the forecast shaking at each location as the common ground to combine all these predictions and introduce a Bayesian approach to creating better ground‐motion predictions. We also describe how this methodology could be used to build a new generation of EEW systems that provide optimal decisions customized for each user based on the user’s individual false‐alarm tolerance and the time necessary for that user to react.

  13. Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based combination therapy from private drug shops in Mukono district, Uganda

    DEFF Research Database (Denmark)

    Hansen, Kristian Schultz; Pedrazzoli, Debora; Mbonye, Anthony

    2013-01-01

    In Uganda, as in many parts of Africa, the majority of the population seek treatment for malaria in drug shops as their first point of care; however, parasitological diagnosis is not usually offered in these outlets. Rapid diagnostic tests (RDTs) for malaria have attracted interest in recent years...... and a course of artemisinin-based combination therapy (ACT) with and without RDT confirmation. Factors associated with WTP were investigated using linear regression. The geometric mean WTP for an RDT was US$0.53, US$1.82 for a course of ACT and US$2.05 for a course of ACT after a positive RDT. Factors strongly...

  14. An evaluation of the clinical diagnostic value of contrast-enhanced ultrasound combined with contrast-enhanced computed tomography in space-occupying lesions of the kidney.

    Science.gov (United States)

    Tian, Wen; Lu, Jianbo; Jiao, Dan; Cong, Zhibin

    2017-01-01

    There are a variety of space-occupying lesions of the kidney, and the benign lesions may be difficult to differentiate from the malignant ones. Therefore, an accurate judgment of the benign and malignant nature of the space-occupying lesions of the kidney is of high importance for the treatment and prognosis of these patients. To evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with contrast-enhanced computed tomography (CECT) in space-occupying lesions of the kidney. Three hundred and sixty-seven patients with space-occupying lesions of the kidney (378 lesions) were examined by CEUS and CECT, respectively, then, a combined diagnosis was made after the combination of CEUS and CECT by a multidisciplinary team. The diagnoses from the three methods were compared. The pathological results were taken as the gold standard. The sensitivity, specificity, positive and negative predictive values and area under the receiver operating characteristic (ROC) curve were calculated for the three methods. Thus, the diagnostic value of the three methods was assessed. Of the 378 lesions examined, there were 301 malignant lesions and 77 benign lesions. The combined examination revealed 303 malignant lesions, with 9 benign lesions mistakenly diagnosed as malignant ones; thus, the misdiagnosis rate was 11.7%. By using the combined examination, 75 benign lesions were diagnosed, with the missed diagnosis of 7 malignant lesions, so the missed diagnosis rate was 2.3%. The sensitivity, specificity, positive and negative predictive values and area under the ROC curve with the combined examination of CEUS and CECT were 97.67% (0.950-0.989), 88.31% (0.785-0.942), 97.03% (0.942-0.985), 90.67% (0.811-0.958) and 0.930 (0.887-0.973), respectively. As compared with either CEUS or CECT alone, the difference in these indicators was of statistical significance (P<0.05). The combined examination greatly improved the sensitivity, specificity and accuracy of the diagnosis of

  15. Analysis of E. rutaecarpa Alkaloids Constituents In Vitro and In Vivo by UPLC-Q-TOF-MS Combined with Diagnostic Fragment

    Directory of Open Access Journals (Sweden)

    Shenshen Yang

    2016-01-01

    Full Text Available Evodia rutaecarpa (Juss. Benth. (Rutaceae dried ripe fruit is used for dispelling colds, soothing liver, and analgesia. Pharmacological research has proved that alkaloids are the main active ingredients of E. rutaecarpa. This study aimed to rapidly classify and identify the alkaloids constituents of E. rutaecarpa by using UPLC-Q-TOF-MS coupled with diagnostic fragments. Furthermore, the effects of the material base of E. rutaecarpa bioactive ingredients in vivo were examined such that the transitional components in the blood of rats intragastrically given E. rutaecarpa were analyzed and identified. In this study, the type of alcohol extraction of E. rutaecarpa and the corresponding blood sample were used for the analysis by UPLC-Q-TOF-MS in positive ion mode. After reviewing much of the literature and collected information on the fragments, we obtained some diagnostic fragments of the alkaloids. Combining the diagnostic fragments with the technology of UPLC-Q-TOF-MS, we identified the compounds of E. rutaecarpa and blood samples and compared the ion fragment information with that of the alkaloids in E. rutaecarpa. A total of 17 alkaloids components and 6 blood components were identified. The proposed method was rapid, accurate, and sensitive. Therefore, this technique can reliably and practically analyze the chemical constituents in traditional Chinese medicine (TCM.

  16. Multiple angles on the sterile neutrino - a combined view of cosmological and oscillation limits

    Science.gov (United States)

    Guzowski, Pawel

    2017-09-01

    The possible existence of sterile neutrinos is an important unresolved question for both particle physics and cosmology. Data sensitive to a sterile neutrino is coming from both particle physics experiments and from astrophysical measurements of the Cosmic Microwave Background. In this study, we address the question whether these two contrasting data sets provide complementary information about sterile neutrinos. We focus on the muon disappearance oscillation channel, taking data from the MINOS, ICECUBE and Planck experiments, converting the limits into particle physics and cosmological parameter spaces, to illustrate the different regions of parameter space where the data sets have the best sensitivity. For the first time, we combine the data sets into a single analysis to illustrate how the limits on the parameters of the sterile-neutrino model are strengthened. We investigate how data from a future accelerator neutrino experiment (SBN) will be able to further constrain this picture.

  17. Heart failure analysis dashboard for patient's remote monitoring combining multiple artificial intelligence technologies.

    Science.gov (United States)

    Guidi, G; Pettenati, M C; Miniati, R; Iadanza, E

    2012-01-01

    In this paper we describe an Heart Failure analysis Dashboard that, combined with a handy device for the automatic acquisition of a set of patient's clinical parameters, allows to support telemonitoring functions. The Dashboard's intelligent core is a Computer Decision Support System designed to assist the clinical decision of non-specialist caring personnel, and it is based on three functional parts: Diagnosis, Prognosis, and Follow-up management. Four Artificial Intelligence-based techniques are compared for providing diagnosis function: a Neural Network, a Support Vector Machine, a Classification Tree and a Fuzzy Expert System whose rules are produced by a Genetic Algorithm. State of the art algorithms are used to support a score-based prognosis function. The patient's Follow-up is used to refine the diagnosis.

  18. Analysis of Multiple Data Hiding Combined Coloured Visual Cryptography and LSB

    Science.gov (United States)

    Maulana, Halim; Rahman Syahputra, Edy

    2017-12-01

    Currently the level of data security becoming a major factor in data transfer. As we know every process of sending data through any medium the risk of that data gets hacked will still be there. Some techniques for securing data such as steganography and cryptography also often used as a solution for securing data. But it does not last long because it has been found out the weaknesses of the algorithm so that the security be assured. So, in need of variety of new algorithms to be able to protect the data so that data security can be guaranteed. In this study tries to combine two visual algorithms that steganography and cryptography. Where in these experiments will try to secure two pieces of data type that is the type of image data and text data where both the data is regarded as a message so to obtain the correct information receiver should get that two types of data.

  19. Encapsulation of Multiple Microalgal Cells via a Combination of Biomimetic Mineralization and LbL Coating

    Directory of Open Access Journals (Sweden)

    Minjeong Kim

    2018-02-01

    Full Text Available The encapsulation of living cells is appealing for its various applications to cell-based sensors, bioreactors, biocatalysts, and bioenergy. In this work, we introduce the encapsulation of multiple microalgal cells in hollow polymer shells of rhombohedral shape by the following sequential processes: embedding of microalgae in CaCO3 crystals; layer-by-layer (LbL coating of polyelectrolytes; and removal of sacrificial crystals. The microcapsule size was controlled by the alteration of CaCO3 crystal size, which is dependent on CaCl2/Na2CO3 concentration. The microalgal cells could be embedded in CaCO3 crystals by a two-step process: heterogeneous nucleation of crystal on the cell surface followed by cell embedment by the subsequent growth of crystal. The surfaces of the microalgal cells were highly favorable for the crystal growth of calcite; thus, micrometer-sized microalgae could be perfectly occluded in the calcite crystal without changing its rhombohedral shape. The surfaces of the microcapsules, moreover, could be decorated with gold nanoparticles, Fe3O4 magnetic nanoparticles, and carbon nanotubes (CNTs, by which we would expect the functionalities of a light-triggered release, magnetic separation, and enhanced mechanical and electrical strength, respectively. This approach, entailing the encapsulation of microalgae in semi-permeable and hollow polymer microcapsules, has the potential for application to microbial-cell immobilization for high-biomass-concentration cultivation as well as various other bioapplications.

  20. Glioblastoma multiforme and papillary thyroid carcinoma - A rare combination of multiple primary malignancies

    Directory of Open Access Journals (Sweden)

    Swaroopa Pulivarthi

    2015-01-01

    Full Text Available We are describing a 19-year-old white woman who presented with two synchronous primary cancers, namely glioblastoma multiforme and papillary thyroid cancer. The patient was admitted with dizziness, headache, and vomiting. CT head revealed acute intraparenchymal hematoma in the right cingulate gyrus and the splenium of the corpus callosum. Carotid and cerebral angiogram were unremarkable. MRI of the brain demonstrated a non-enhancing and non-hemorrhagic component of the lesion along the lateral margin of the hemorrhage just medial to the atrium of the right lateral ventricle that was suspicious for a tumor or metastasis. Brain biopsy confirmed it as glioblastoma mutiforme. CT chest was done to rule out primary cancer that revealed a 11 mm hypodense lesion in the left lobe of the thyroid and ultrasound-guided fine-needle aspiration biopsy confirmed it as papillary thyroid carcinoma. We should evaluate for multiple primary malignancies in young patients who are found to have primary index cancer.

  1. Encapsulation of Multiple Microalgal Cells via a Combination of Biomimetic Mineralization and LbL Coating.

    Science.gov (United States)

    Kim, Minjeong; Choi, Myoung Gil; Ra, Ho Won; Park, Seung Bin; Kim, Yong-Joo; Lee, Kyubock

    2018-02-13

    The encapsulation of living cells is appealing for its various applications to cell-based sensors, bioreactors, biocatalysts, and bioenergy. In this work, we introduce the encapsulation of multiple microalgal cells in hollow polymer shells of rhombohedral shape by the following sequential processes: embedding of microalgae in CaCO₃ crystals; layer-by-layer (LbL) coating of polyelectrolytes; and removal of sacrificial crystals. The microcapsule size was controlled by the alteration of CaCO₃ crystal size, which is dependent on CaCl₂/Na₂CO₃ concentration. The microalgal cells could be embedded in CaCO₃ crystals by a two-step process: heterogeneous nucleation of crystal on the cell surface followed by cell embedment by the subsequent growth of crystal. The surfaces of the microalgal cells were highly favorable for the crystal growth of calcite; thus, micrometer-sized microalgae could be perfectly occluded in the calcite crystal without changing its rhombohedral shape. The surfaces of the microcapsules, moreover, could be decorated with gold nanoparticles, Fe₃O₄ magnetic nanoparticles, and carbon nanotubes (CNTs), by which we would expect the functionalities of a light-triggered release, magnetic separation, and enhanced mechanical and electrical strength, respectively. This approach, entailing the encapsulation of microalgae in semi-permeable and hollow polymer microcapsules, has the potential for application to microbial-cell immobilization for high-biomass-concentration cultivation as well as various other bioapplications.

  2. Combining hidden Markov models for comparing the dynamics of multiple sleep electroencephalograms.

    Science.gov (United States)

    Langrock, Roland; Swihart, Bruce J; Caffo, Brian S; Punjabi, Naresh M; Crainiceanu, Ciprian M

    2013-08-30

    In this manuscript, we consider methods for the analysis of populations of electroencephalogram signals during sleep for the study of sleep disorders using hidden Markov models (HMMs). Notably, we propose an easily implemented method for simultaneously modeling multiple time series that involve large amounts of data. We apply these methods to study sleep-disordered breathing (SDB) in the Sleep Heart Health Study (SHHS), a landmark study of SDB and cardiovascular consequences. We use the entire, longitudinally collected, SHHS cohort to develop HMM population parameters, which we then apply to obtain subject-specific Markovian predictions. From these predictions, we create several indices of interest, such as transition frequencies between latent states. Our HMM analysis of electroencephalogram signals uncovers interesting findings regarding differences in brain activity during sleep between those with and without SDB. These findings include stability of the percent time spent in HMM latent states across matched diseased and non-diseased groups and differences in the rate of transitioning. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Aging Airways: between Normal and Disease. A Multidimensional Diagnostic Approach by Combining Clinical, Functional, and Imaging Data.

    Science.gov (United States)

    Occhipinti, Mariaelena; Larici, Anna Rita; Bonomo, Lorenzo; Incalzi, Raffaele Antonelli

    2017-07-01

    The lack of data on lung function decline in the aging process as well as the lack of gold standards to define obstructive and restrictive respiratory disease in older people point out the need for a multidimensional assessment and interpretation of the aging airways. By integrating clinical data together with morphologic and morphometric findings clinicians can assess the airways with a more comprehensive perspective, helpful in the interpretation of the "grey zone" between normal aging and disease. This review focuses on the value of a multidimensional approach in the study of the aging airways, including clinical findings, respiratory function tests, and imaging as parts of a whole. Nowadays this multidimensional diagnostic approach can be used in daily clinical practice. In next future, it can be implemented by the analysis of exhaled gases, post-processing imaging techniques, and genetic analysis, that will hopefully reduce the gaps in knowledge of normal aging and airway disease in older people.

  4. ¹⁸F-FDG PET/CT: a review of diagnostic and prognostic features in multiple myeloma and related disorders.

    Science.gov (United States)

    Dammacco, Franco; Rubini, Giuseppe; Ferrari, Cristina; Vacca, Angelo; Racanelli, Vito

    2015-02-01

    Conventional radiographic skeletal survey has been for many years the gold standard to detect the occurrence of osteolytic lesions in patients with multiple myeloma (MM). However, the introduction of more sensitive imaging procedures has resulted in an updated anatomic and functional Durie and Salmon "plus" staging system and has remarkably changed the diagnostic and prognostic approach to this tumor. It is now established that (18)fluorine-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography (PET) combined with low-dose computed tomography (CT), shortly designated PET/CT, exhibits a higher screening and diagnostic sensitivity and specificity over the skeleton X-ray. In patients with monoclonal gammopathy of undetermined significance and in those with smoldering MM, PET/CT is consistently unable to detect focal and/or diffuse marrow abnormalities. Conversely, based on a systematic review of 18 studies comprising almost 800 MM patients, PET/CT was able to detect MM osteolytic lesions with a sensitivity of approximately 80-90% and a specificity of 80-100%. Importantly, a poor degree of concordance has also been emphasized between PET/CT and whole-body magnetic resonance imaging (WB-MRI) in that when both techniques were applied to the same patients, double-positive results were recorded in approximately 30% of the cases, but in the majority of them, a higher number of lesions were revealed with PET/CT than with MRI. Double-negative results, on the other hand, were found in about 22% of the patients. Because PET/CT is able to identify tumor foci throughout the body, it can be usefully applied to the study of solitary bone plasmacytoma and extra-medullary plasmacytoma: In both conditions, the detection of additional, previously overlooked sites of skeletal involvement would falsify the diagnosis of single-district disease, upstage the tumor, and therefore require a different therapeutic approach. In addition, although PET/CT is poorly sensitive to diffuse bone

  5. Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

    Directory of Open Access Journals (Sweden)

    Yoon-Dong Park

    2016-08-01

    Full Text Available Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development.

  6. Combined Raman and autofluorescence ex vivo diagnostics of skin cancer in near-infrared and visible regions

    Science.gov (United States)

    Bratchenko, Ivan A.; Artemyev, Dmitry N.; Myakinin, Oleg O.; Khristoforova, Yulia A.; Moryatov, Alexander A.; Kozlov, Sergey V.; Zakharov, Valery P.

    2017-02-01

    The differentiation of skin melanomas and basal cell carcinomas (BCCs) was demonstrated based on combined analysis of Raman and autofluorescence spectra stimulated by visible and NIR lasers. It was ex vivo tested on 39 melanomas and 40 BCCs. Six spectroscopic criteria utilizing information about alteration of melanin, porphyrins, flavins, lipids, and collagen content in tumor with a comparison to healthy skin were proposed. The measured correlation between the proposed criteria makes it possible to define weakly correlated criteria groups for discriminant analysis and principal components analysis application. It was shown that the accuracy of cancerous tissues classification reaches 97.3% for a combined 6-criteria multimodal algorithm, while the accuracy determined separately for each modality does not exceed 79%. The combined 6-D method is a rapid and reliable tool for malignant skin detection and classification.

  7. On Combining Multiple-Instance Learning and Active Learning for Computer-Aided Detection of Tuberculosis.

    Science.gov (United States)

    Melendez, Jaime; van Ginneken, Bram; Maduskar, Pragnya; Philipsen, Rick H H M; Ayles, Helen; Sanchez, Clara I

    2016-04-01

    The major advantage of multiple-instance learning (MIL) applied to a computer-aided detection (CAD) system is that it allows optimizing the latter with case-level labels instead of accurate lesion outlines as traditionally required for a supervised approach. As shown in previous work, a MIL-based CAD system can perform comparably to its supervised counterpart considering complex tasks such as chest radiograph scoring in tuberculosis (TB) detection. However, despite this remarkable achievement, the uncertainty inherent to MIL can lead to a less satisfactory outcome if analysis at lower levels (e.g., regions or pixels) is needed. This issue may seriously compromise the applicability of MIL to tasks related to quantification or grading, or detection of highly localized lesions. In this paper, we propose to reduce uncertainty by embedding a MIL classifier within an active learning (AL) framework. To minimize the labeling effort, we develop a novel instance selection mechanism that exploits the MIL problem definition through one-class classification. We adapt this mechanism to provide meaningful regions instead of individual instances for expert labeling, which is a more appropriate strategy given the application domain. In addition, and contrary to usual AL methods, a single iteration is performed. To show the effectiveness of our approach, we compare the output of a MIL-based CAD system trained with and without the proposed AL framework. The task is to detect textural abnormalities related to TB. Both quantitative and qualitative evaluations at the pixel level are carried out. Our method significantly improves the MIL-based classification.

  8. Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Ikeda H

    2015-10-01

    Full Text Available Hiroshi Ikeda,1 Kazuya Ishiguro,1 Tetsuyuki Igarashi,1 Yuka Aoki,1 Toshiaki Hayashi,1 Tadao Ishida,1 Yasushi Sasaki,1,2 Takashi Tokino,2 Yasuhisa Shinomura1 1Department of Gastroenterology, Rheumatology and Clinical Immunology, 2Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan Abstract: A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM, Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients. Keywords: multiple myeloma, drug resistance, genome-wide sequencing, semiconductor sequencer, target therapy

  9. IPeak: An open source tool to combine results from multiple MS/MS search engines.

    Science.gov (United States)

    Wen, Bo; Du, Chaoqin; Li, Guilin; Ghali, Fawaz; Jones, Andrew R; Käll, Lukas; Xu, Shaohang; Zhou, Ruo; Ren, Zhe; Feng, Qiang; Xu, Xun; Wang, Jun

    2015-09-01

    Liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) is an important technique for detecting peptides in proteomics studies. Here, we present an open source software tool, termed IPeak, a peptide identification pipeline that is designed to combine the Percolator post-processing algorithm and multi-search strategy to enhance the sensitivity of peptide identifications without compromising accuracy. IPeak provides a graphical user interface (GUI) as well as a command-line interface, which is implemented in JAVA and can work on all three major operating system platforms: Windows, Linux/Unix and OS X. IPeak has been designed to work with the mzIdentML standard from the Proteomics Standards Initiative (PSI) as an input and output, and also been fully integrated into the associated mzidLibrary project, providing access to the overall pipeline, as well as modules for calling Percolator on individual search engine result files. The integration thus enables IPeak (and Percolator) to be used in conjunction with any software packages implementing the mzIdentML data standard. IPeak is freely available and can be downloaded under an Apache 2.0 license at https://code.google.com/p/mzidentml-lib/. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Therapy of Severe Heatshock in Combination With Multiple Organ Dysfunction With Continuous Renal Replacement Therapy

    Science.gov (United States)

    Chen, Guang-Ming; Chen, Yang-Hong; Zhang, Wei; Yu, Yi; Chen, Jin-Hua; Chen, Jian

    2015-01-01

    Abstract This study aimed to compare the clinical effects of continuous renal replacement therapy (CRRT) and routine therapy in heatshock (HS) patients. We retrospectively reviewed the clinical information of 33 severe exertional HS patients who were treated from February 1998 to October 2013. On the basis of whether or not CRRT therapy was used in addition to conventional therapy, patients were divided into a CRRT group (n = 15) and a control group (n = 18). Body temperature, blood gas analysis, routine blood tests, blood eletrolytes, enzymes and kidney function data, and APACHE II scores were obtained and compared between the 2 groups on admission and 3, 5, and 7 days after admission. Mortality was also compared between the 2 groups. CRRT treatment combined with conventional treatment resulted in a higher hospital-discharge rate, a faster return to normal of body temperature, greater increase in platelets, a greater decrease in WBC, neutrophils, and serum markers for liver and kidney dysfunction, greater improvement of organ dysfunction, and lower APACHE II scores than conventional treatment used alone. The addition of CRRT to conventional treatment for HS improves survival and causes a faster return to normal of serum markers and organ function. PMID:26252279

  11. Multiple pesticide analysis in wine by MEKC combined with solid-phase microextraction and sample stacking.

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    Ravelo-Pérez, Lidia M; Hernández-Borges, Javier; Borges-Miquel, Teresa M; Rodríguez-Delgado, Miguel A

    2007-11-01

    In this work, a new method for the determination in white wines of 12 pesticides widely used in vine cultivars (namely, carbendazim, pirimicarb, metalaxyl, pyrimethanil, procymidone, nuarimol, azoxystrobin, tebufenozide, fenarimol, benalaxyl, penconazole, and tetradifon) using solid-phase microextraction (SPME) and MEKC with diode-array detection (DAD) was developed. The MEKC buffer consisted of 100 mM sodium tetraborate and 30 mM SDS at pH 8.5 with 6% v/v 1-propanol. Reversed-electrode polarity stacking mode (REPSM) was applied as on-line preconcentration strategy. In order to carry out an effective and sensitive determination of these pesticides in wine samples, an off-line SPME procedure was optimized by means of an experimental design. After studying the extraction performance of different SPME coatings, PDMS/divinylbenzene (PDMS/DVB) fibers were found the most appropriate for the extraction of most of these pesticides. Carbendazim and metalaxyl could not be extracted from wine samples. Calibration curves for extracted standards and fortified white wines were studied in order to determine the presence of a matrix effect. The combination of both preconcentration procedures (SPME and REPSM) allowed the determination of ten of these pesticides in white wines at concentrations between 0.054 and 0.113 mg/L. (i.e., levels well below the maximum residue limits (MRLs) allowed for these compounds in wine grapes). Ten homemade wines were they analyzed with the optimized method demonstrating the usefulness of the proposed procedure.

  12. Multiple-platform data integration method with application to combined analysis of microarray and proteomic data

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    Wu Shicheng

    2012-12-01

    Full Text Available Abstract Background It is desirable in genomic studies to select biomarkers that differentiate between normal and diseased populations based on related data sets from different platforms, including microarray expression and proteomic data. Most recently developed integration methods focus on correlation analyses between gene and protein expression profiles. The correlation methods select biomarkers with concordant behavior across two platforms but do not directly select differentially expressed biomarkers. Other integration methods have been proposed to combine statistical evidence in terms of ranks and p-values, but they do not account for the dependency relationships among the data across platforms. Results In this paper, we propose an integration method to perform hypothesis testing and biomarkers selection based on multi-platform data sets observed from normal and diseased populations. The types of test statistics can vary across the platforms and their marginal distributions can be different. The observed test statistics are aggregated across different data platforms in a weighted scheme, where the weights take into account different variabilities possessed by test statistics. The overall decision is based on the empirical distribution of the aggregated statistic obtained through random permutations. Conclusion In both simulation studies and real biological data analyses, our proposed method of multi-platform integration has better control over false discovery rates and higher positive selection rates than the uncombined method. The proposed method is also shown to be more powerful than rank aggregation method.

  13. Incremental Cancer Detection of Locoregional Restaging with Diagnostic Mammography Combined with Whole-Breast and Regional Nodal Ultrasound in Women with Newly Diagnosed Breast Cancer.

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    Candelaria, Rosalind P; Huang, Monica L; Adrada, Beatriz E; Bassett, Roland; Hunt, Kelly K; Kuerer, Henry M; Smith, Benjamin D; Chavez-MacGregor, Mariana; Yang, Wei Tse

    2017-02-01

    This study aims to determine if locoregional restaging with diagnostic mammography and ultrasound (US) of the whole breast and regional nodes performed for quality assurance in women with newly diagnosed breast cancer who were referred to a tertiary care center yields incremental cancer detection. An institutional review board-approved retrospective, single-institution database review was performed on the first 1000 women referred to our center in 2010 with a provisional breast cancer diagnosis. Locoregional restaging consisted of diagnostic full-field digital mammography combined with US of the whole breast and regional nodal basins. Bilateral whole-breast US was performed in women with contralateral mammographic abnormality or had heterogeneously or extremely dense parenchyma. Demographic, clinical, and pathologic factors were analyzed. Final analyses included 401 women. Of the 401 women, 138 (34%) did not have their outside images available for review upon referral. The median age was 54 years (range 21-92); the median tumor size was 2.9 cm (range 0.6-18.0) for women whose disease was upstaged and 2.2 cm (range 0.4-15.0) for women whose disease was not upstaged. Incremental cancer detection rates were 15.5% (62 of 401) in the ipsilateral breast and 3.9% (6 of 154) in the contralateral breast (P < 0.0001). The total upstage rate was 25% (100 of 401). Surgical management changed from segmentectomy to mastectomy in 12% (50 of 401). The re-excision rate after segmentectomy was 19% (35 of 189). Locoregional restaging with diagnostic mammography combined with whole-breast and regional nodal US that is performed for standardization of the imaging workup for newly diagnosed breast cancer patients can reduce underestimation of disease burden and impact therapeutic planning. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  14. Patients with Intolerance Reactions to Total Knee Replacement: Combined Assessment of Allergy Diagnostics, Periprosthetic Histology, and Peri-implant Cytokine Expression Pattern

    Directory of Open Access Journals (Sweden)

    Peter Thomas

    2015-01-01

    Full Text Available We performed a combined approach to identify suspected allergy to knee arthroplasty (TKR: patch test (PT, lymphocyte transformation test (LTT, histopathology (overall grading; T- and B-lymphocytes, macrophages, and neutrophils, and semiquantitative Real-time-PCR-based periprosthetic inflammatory mediator analysis (IFNγ, TNFα, IL1-β, IL-2, IL-6, IL-8, IL-10, IL17, and TGFβ. We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion. They consisted of 20 patients with proven metal sensitization (11 with PT reactions; 9 with only LTT reactivity. Control specimens were from 5 complicated TKR patients without metal sensitization, 12 OA patients before arthroplasty, and 8 PT patients without arthroplasty. Lymphocytic infiltrates were seen and fibrotic (Type IV membrane tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients. The latter also had marked periprosthetic IFNγ expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief. Our findings demonstrate that combining allergy diagnostics with histopathology and periprosthetic cytokine assessment could allow us to design better diagnostic strategies.

  15. Comparison of opportunities to respond and generation effect as potential causal mechanisms for incremental rehearsal with multiplication combinations.

    Science.gov (United States)

    Zaslofsky, Anne F; Scholin, Sarah E; Burns, Matthew K; Varma, Sashank

    2016-04-01

    Incremental rehearsal (IR) is an intervention with demonstrated effectiveness in increasing retention of information, yet little is known about how specific intervention components contribute to the intervention's effectiveness. The purpose of this study was to further the theoretical understanding of the intervention by comparing the effects of opportunities to respond (OTR) and generation demand on retention of multiplication combinations. Using a between subject 2 × 2 factorial design, 103 4th and 5th grade students were taught seven multiplication combinations using one of four versions of IR that orthogonally varied OTR (high versus low) and generation demands (high versus low). A two-way ANOVA revealed main effects for OTR, generation demands, and an interaction of the two factors. The effect of generation demands was large (d=1.31), whereas the overall effect of OTR was moderate (d=0.66). Critically, the two factors interacted, with the largest learning gains observed when OTR and generation demands were both high. The results of this study suggest that generation demand is an important factor in the effectiveness of rehearsal interventions. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  16. Predicting Protein-DNA Binding Residues by Weightedly Combining Sequence-Based Features and Boosting Multiple SVMs.

    Science.gov (United States)

    Hu, Jun; Li, Yang; Zhang, Ming; Yang, Xibei; Shen, Hong-Bin; Yu, Dong-Jun

    2017-01-01

    Protein-DNA interactions are ubiquitous in a wide variety of biological processes. Correctly locating DNA-binding residues solely from protein sequences is an important but challenging task for protein function annotations and drug discovery, especially in the post-genomic era where large volumes of protein sequences have quickly accumulated. In this study, we report a new predictor, named TargetDNA, for targeting protein-DNA binding residues from primary sequences. TargetDNA uses a protein's evolutionary information and its predicted solvent accessibility as two base features and employs a centered linear kernel alignment algorithm to learn the weights for weightedly combining the two features. Based on the weightedly combined feature, multiple initial predictors with SVM as classifiers are trained by applying a random under-sampling technique to the original dataset, the purpose of which is to cope with the severe imbalance phenomenon that exists between the number of DNA-binding and non-binding residues. The final ensembled predictor is obtained by boosting the multiple initially trained predictors. Experimental simulation results demonstrate that the proposed TargetDNA achieves a high prediction performance and outperforms many existing sequence-based protein-DNA binding residue predictors. The TargetDNA web server and datasets are freely available at http://csbio.njust.edu.cn/bioinf/TargetDNA/ for academic use.

  17. Serum antithrombin III level is well correlated with multiple indicators for assessment of liver function and diagnostic accuracy for predicting postoperative liver failure in hepatocellular carcinoma patients.

    Science.gov (United States)

    Mizuguchi, Toru; Kawamoto, Masaki; Meguro, Makoto; Son, Seiichi; Nakamura, Yukio; Harada, Kohei; Shibata, Toshihito; Ota, Shigenori; Hirata, Koichi

    2012-01-01

    Evaluation of preoperative hepatic reserve is critical to avoid a fatal clinical course such as liver failure. We retrospectively evaluated 158 consecutive hepatocellular carcinoma (HCC) patients who underwent initial hepatectomy. The aim of this study was to determine the correlations of multiple indicators for assessment of liver function before hepatectomy. Furthermore, diagnostic probability for the pathological background and prediction of postoperative liver failure/dysfunction was compared between the antithrombin (AT) III level and indocyanine green retention rate at 15 minutes (ICGR15). Between January 2001 and March 2008, 158 HCC patients who underwent initial hepatectomy were enrolled in this study. Spearman's correlation coefficients (r values) were obtained for 15 clinical laboratory tests including ATIII and ICGR15. Receiver operating characteristic (ROC) curve analysis was used for calculating the probability and predictive ability of the tests. All 158 consecutive HCC patients were eligible for hepatectomy based on the Japanese guideline. ATIII is correlated with 13 of 14 other clinical tests, including albumin, bilirubin, prothrombin time, rapid turnover proteins, HGF, ICGR15 and others. The diagnostic probabilities to distinguish between normal liver and other pathological backgrounds of ATIII and ICGR15 were significantly different. The specificity of ATIII to predict postoperative liver failure/dysfunction was higher than that of ICGR15. The serum ATIII level before hepatectomy is valuable to estimate the pathological background and predict postoperative liver failure/ dysfunction. It should be possible to use ATIII as an additional indicator for liver function and substitute for ICGR15 in the future.

  18. Deriving utility scores for co-morbid conditions: a test of the multiplicative model for combining individual condition scores

    Directory of Open Access Journals (Sweden)

    Le Petit Christel

    2006-10-01

    Full Text Available Abstract Background The co-morbidity of health conditions is becoming a significant health issue, particularly as populations age, and presents important methodological challenges for population health research. For example, the calculation of summary measures of population health (SMPH can be compromised if co-morbidity is not taken into account. One popular co-morbidity adjustment used in SMPH computations relies on a straightforward multiplicative combination of the severity weights for the individual conditions involved. While the convenience and simplicity of the multiplicative model are attractive, its appropriateness has yet to be formally tested. The primary objective of the current study was therefore to examine the empirical evidence in support of this approach. Methods The present study drew on information on the prevalence of chronic conditions and a utility-based measure of health-related quality of life (HRQoL, namely the Health Utilities Index Mark 3 (HUI3, available from Cycle 1.1 of the Canadian Community Health Survey (CCHS; 2000–01. Average HUI3 scores were computed for both single and co-morbid conditions, and were also purified by statistically removing the loss of functional health due to health problems other than the chronic conditions reported. The co-morbidity rule was specified as a multiplicative combination of the purified average observed HUI3 utility scores for the individual conditions involved, with the addition of a synergy coefficient s for capturing any interaction between the conditions not explained by the product of their utilities. The fit of the model to the purified average observed utilities for the co-morbid conditions was optimized using ordinary least squares regression to estimate s. Replicability of the results was assessed by applying the method to triple co-morbidities from the CCHS cycle 1.1 database, as well as to double and triple co-morbidities from cycle 2.1 of the CCHS (2003–04. Results

  19. Advances in Human Biology: Combining Genetics and Molecular Biophysics to Pave the Way for Personalized Diagnostics and Medicine

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    Emil Alexov

    2014-01-01

    Full Text Available Advances in several biology-oriented initiatives such as genome sequencing and structural genomics, along with the progress made through traditional biological and biochemical research, have opened up a unique opportunity to better understand the molecular effects of human diseases. Human DNA can vary significantly from person to person and determines an individual’s physical characteristics and their susceptibility to diseases. Armed with an individual’s DNA sequence, researchers and physicians can check for defects known to be associated with certain diseases by utilizing various databases. However, for unclassified DNA mutations or in order to reveal molecular mechanism behind the effects, the mutations have to be mapped onto the corresponding networks and macromolecular structures and then analyzed to reveal their effect on the wild type properties of biological processes involved. Predicting the effect of DNA mutations on individual’s health is typically referred to as personalized or companion diagnostics. Furthermore, once the molecular mechanism of the mutations is revealed, the patient should be given drugs which are the most appropriate for the individual genome, referred to as pharmacogenomics. Altogether, the shift in focus in medicine towards more genomic-oriented practices is the foundation of personalized medicine. The progress made in these rapidly developing fields is outlined.

  20. Combined Inoculation with Multiple Arbuscular Mycorrhizal Fungi Improves Growth, Nutrient Uptake and Photosynthesis in Cucumber Seedlings

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    Shuangchen Chen

    2017-12-01

    Full Text Available Mycorrhizal inoculation stimulates growth, photosynthesis and nutrient uptake in a wide range of host plants. However, the ultimate effects of arbuscular mycorrhyzal (AM symbiosis vary with the plants and fungal species involved in the association. Therefore, identification of the appropriate combinations of AM fungi (AMF that interact synergistically to improve their benefits is of high significance. Here, three AM fungal compositions namely VT (Claroideoglomus sp., Funneliformis sp., Diversispora sp., Glomus sp., and Rhizophagus sp. and BF (Glomus intraradices, G. microageregatum BEG and G. Claroideum BEG 210, and Funneliformis mosseae (Fm were investigated with respect to the growth, gas exchange parameters, enzymes activities in Calvin cycles and related gene expression in cucumber seedlings. The results showed that VT, BF and Fm could successfully colonize cucumber root to a different degree with the colonization rates 82.38, 74.65, and 70.32% at 46 days post inoculation, respectively. The plant height, stem diameter, dry weight, root to shoot ratio of cucumber seedlings inoculated with AMF increased significantly compared with the non-inoculated control. Moreover, AMF colonization greatly increased the root activity, chlorophyll content, net photosynthetic rate, light saturated rate of the CO2 assimilation (Asat, maximum carboxylation rate (Vcmax and maximum ribulose-1,5-bis-phosphate (RuBP regeneration rate (Jmax, which were increased by 52.81, 30.75, 58.76, 47.00, 69.15, and 65.53% when inoculated with VT, respectively. The activities of some key enzymes such RuBP carboxylase/oxygenase (RuBisCO, D-fructose-1,6-bisphosphatase (FBPase, D-fructose-6-phosphatase (F6P and ribulose-5-phosphate kinase (Ru5PK, and related gene expression involved in the Calvin cycle including RCA, FBPase, FBPA, SBPase, rbcS and rbcL were upregulated by AMF colonization. AMF inoculation also improved macro- and micro nutrient contents such as N, P, K, S, Ca, Cu

  1. Considerations when combining data from multiple nutrition experiments to estimate genetic parameters for feed efficiency.

    Science.gov (United States)

    Hardie, L C; Armentano, L E; Shaver, R D; VandeHaar, M J; Spurlock, D M; Yao, C; Bertics, S J; Contreras-Govea, F E; Weigel, K A

    2015-04-01

    Prior to genomic selection on a trait, a reference population needs to be established to link marker genotypes with phenotypes. For costly and difficult-to-measure traits, international collaboration and sharing of data between disciplines may be necessary. Our aim was to characterize the combining of data from nutrition studies carried out under similar climate and management conditions to estimate genetic parameters for feed efficiency. Furthermore, we postulated that data from the experimental cohorts within these studies can be used to estimate the net energy of lactation (NE(L)) densities of diets, which can provide estimates of energy intakes for use in the calculation of the feed efficiency metric, residual feed intake (RFI), and potentially reduce the effect of variation in energy density of diets. Individual feed intakes and corresponding production and body measurements were obtained from 13 Midwestern nutrition experiments. Two measures of RFI were considered, RFI(Mcal) and RFI(kg), which involved the regression of NE(L )intake (Mcal/d) or dry matter intake (DMI; kg/d) on 3 expenditures: milk energy, energy gained or lost in body weight change, and energy for maintenance. In total, 677 records from 600 lactating cows between 50 and 275 d in milk were used. Cows were divided into 46 cohorts based on dietary or nondietary treatments as dictated by the nutrition experiments. The realized NE(L) densities of the diets (Mcal/kg of DMI) were estimated for each cohort by totaling the average daily energy used in the 3 expenditures for cohort members and dividing by the cohort's total average daily DMI. The NE(L) intake for each cow was then calculated by multiplying her DMI by her cohort's realized energy density. Mean energy density was 1.58 Mcal/kg. Heritability estimates for RFI(kg), and RFI(Mcal) in a single-trait animal model did not differ at 0.04 for both measures. Information about realized energy density could be useful in standardizing intake data from

  2. Diagnostic accuracy of combined cardiac troponin and copeptin assessment for early rule-out of myocardial infarction: a systematic review and meta-analysis

    Science.gov (United States)

    Raskovalova, Tatiana; Twerenbold, Raphael; Collinson, Paul O; Keller, Till; Bouvaist, Hélène; Folli, Christian; Giavarina, Davide; Lotze, Ulrich; Eggers, Kai M; Dupuy, Anne-Marie; Chenevier-Gobeaux, Camille; Meune, Christophe; Maisel, Alan; Mueller, Christian

    2014-01-01

    Aims: This systematic review aimed to investigate the diagnostic accuracy of combined cardiac troponin (cTn) and copeptin assessment in comparison to cTn alone for early rule-out of acute myocardial infarction (AMI). Methods: Primary studies were eligible if they evaluated diagnostic accuracy for cTn with and without copeptin in patients with symptoms suggestive of AMI. AMI was defined according to the universal definition, using detection of cTn as a marker for myocardial necrosis. Eligible studies were identified by searching electronic databases (Medline, EMBASE, Science Citation Index Expanded, CINAHL, Pascal, and Cochrane) from inception to March 2013, reviewing conference proceedings and contacting field experts and the copeptin manufacturer. Results: In 15 studies totalling 8740 patients (prevalence of AMI 16%), adding copeptin improved the sensitivity of cTn assays (from 0.87 to 0.96, p=0.003) at the expense of lower specificity (from 0.84 to 0.56, pcopeptin. When a high-sensitivity cTnT assay was used in combination with copeptin, the summary sensitivity and specificity estimates were 0.98 (95% CI 0.96 to 1.00) and 0.50 (95% CI 0.42 to 0.58). Conclusion: Despite substantial between-study heterogeneity, this meta-analysis demonstrates that copeptin significantly improves baseline cTn sensitivity. Management studies are needed to establish the effectiveness and safety of measuring copeptin in combination with high-sensitivity cTnT for early rule-out of AMI without serial testing. PMID:24562800

  3. MAGEA4 expression in bone and soft tissue tumors: its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1.

    Science.gov (United States)

    Iura, Kunio; Kohashi, Kenichi; Ishii, Takeaki; Maekawa, Akira; Bekki, Hirofumi; Otsuka, Hiroshi; Yamada, Yuichi; Yamamoto, Hidetaka; Matsumoto, Yoshihiro; Iwamoto, Yukihide; Oda, Yoshinao

    2017-07-26

    Cancer-testis (CT) antigens have promise as targets for immunotherapy, because of their restricted expression in tumor or testis tissue. MAGEA4 is both a MAGE family member and a CT antigen, and has attracted attention as a potential immunotherapeutic target. We investigated MAGEA4 expression by immunohistochemistry in bone and soft tissue tumor specimens that consisted of 35 malignant or intermediate and 24 benign histological subtypes, in order to evaluate its possible utility as an immunotherapy target and its potential use as a diagnostic marker when combined with another CT antigen, NY-ESO-1. Among these tumors, MAGEA4 was detected in 82.2% of synovial sarcomas, 67.7% of myxoid liposarcomas, 43.8% of osteosarcomas, 41.4% of angiosarcomas, 24.6% of malignant peripheral nerve sheath tumors (MPNSTs), and 21.4% of chondrosarcomas. NY-ESO-1 expression was found in 88.2% of myxoid liposarcomas, 61.1% of synovial sarcomas, 31.3% of osteosarcomas, 21.4% of pleomorphic liposarcomas, 16.7% of desmoplastic small round cell tumors, and 14.3% of chondrosarcomas. Benign tumors and non-tumorous tissue, except for testis tissue, did not express MAGEA4 or NY-ESO-1. Combined use of MAGEA4 and NY-ESO-1 increased the sensitivity, specificity, positive predictive values, and negative predictive values for distinguishing synovial sarcoma from spindle cell tumors and other mimicking tumors, compared to individual use of MAGEA4 or NY-ESO-1. Our results support the immunotherapy targeting MAGEA4 or NY-ESO-1 can be an ancillary therapy in the above-mentioned tumors, and the potential utility of MAGEA4 as an ancillary diagnostic marker for synovial sarcoma combined with NY-ESO-1.

  4. Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients.

    Science.gov (United States)

    Lim, Tae Seop; Kim, Do Young; Han, Kwang-Hyub; Kim, Hyon-Suk; Shin, Seung Hwan; Jung, Kyu Sik; Kim, Beom Kyung; Kim, Seung Up; Park, Jun Yong; Ahn, Sang Hoon

    2016-03-01

    As data on the effectiveness of tumor markers in detecting hepatocellular carcinoma (HCC) in cirrhotic patients are limited, we investigated the diagnostic accuracy of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3). This retrospective study enrolled 361 cirrhotic patients with HCC, and 276 cirrhotic patients without HCC occurrence. Most patients were men (n = 431, 67.7%); the median age was 57.0 years. The main etiology of chronic liver disease was chronic hepatitis B (n = 467, 73.3%). The sensitivity and specificity of combined three biomarkers was 87.0 and 60.1% in overall HCC, and 75.7 and 60.1% in early HCC, respectively (cutoff: 20 ng/mL for AFP, 40 mAU/mL for PIVKA-II, and 5% for AFP-L3). The area under the receiver operating characteristic curve (AUROC) for HCC diagnosis was 0.765 (95% confidence interval [CI], 0.728-0.801) for AFP; 0.823 (95% CI, 0.791-0.854) for PIVKA-II; and 0.755 (95% CI, 0.718-0.792) for AFP-L3. The AUROC for early HCC diagnosis was 0.754 (95% CI, 0.691-0.816) for AFP, 0.701 (95% CI, 0.630-0.771) for PIVKA-II, and 0.670 (95% CI, 0.596-0.744) for AFP-L3. Combining the three tumor markers increased the AUROC to 0.877 (95% CI, 0.851-0.903) for HCC diagnosis, and 0.773 (95% CI, 0.704-0.841) for early HCC diagnosis. Diagnostic accuracy improved upon combining the AFP, PIVKA-II, and AFP-L3 tumor markers compared to each marker alone in detecting HCC and early HCC in cirrhotic patients.

  5. The Effect of Multiple Sulfatase Deficiency (MSD) on Dental Development: Can We Use the Teeth as an Early Diagnostic Tool?

    Science.gov (United States)

    Zilberman, Uri; Bibi, Haim

    2016-01-01

    Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of metabolism due to reduced catalytic activity of the different sulfatase. Affected individuals show neurologic deterioration with mental retardation, skeletal anomalies, organomegaly, and skin changes as in X-linked ichthyosis. The only organ that was not examined in MSD patients is the dentition. To evaluate the effect of the metabolic error on dental development in a patient with the intermediate severe late-infantile form of MSD (S155P). Histological and chemical study were performed on three deciduous and five permanent teeth from MSD patient and pair-matched normal patients. Tooth germ size and enamel thickness were reduced in both deciduous and permanent MSD teeth, and the scalloping feature of the DEJ was missing in MSD teeth causing enamel to break off from the dentin. The mineral components in the enamel and dentin were different. The metabolic error insults the teeth in the stage of organogenesis in both the deciduous and permanent dentition. The end result is teeth with very sharp cusp tips, thin hypomineralized enamel, and exposed dentin due to the break off of enamel. These findings are different from all other types of MPS syndromes.Clinically the phenotype of intermediate severe late-infantile form of MSD appeared during the third year of life. In children of parents that are carriers, we can diagnose the disease as early as birth using X-ray radiograph of the anterior upper region or as early as 6-8 months when the first deciduous tooth erupt and consider very early treatment to ameliorate the symptoms.

  6. Persistent upper airway obstruction is a diagnostic feature of spondyloepimetaphyseal dysplasia with multiple dislocations (Hall type) with further evidence for dominant inheritance.

    Science.gov (United States)

    Park, Soo-Mi; Hall, Christine M; Gray, Roger; Firth, Helen V

    2007-09-01

    The spondyloepimetaphyseal dysplasias (SEMD) are a group of skeletal dysplasias of variable severity with a heterogeneous genetic aetiology. SEMD with multiple dislocations (Hall type) is a recently identified disorder (OMIM 603546) which is characterized by striking epiphyseal and metaphyseal changes of the long bones and joint laxity with multiple dislocations of the large joints. We report on persistent inspiratory stridor in a child with this type of SEMD in the second reported family with dominant transmission of this disorder. Microlaryngoscopy showed laryngeal stenosis due to failure of abduction of the vocal cords and a tracheostomy was required to provide a satisfactory airway. Since airway compromise has been reported previously in a small series of patients (total of five out of 13 cases so far), the evidence to date supports the association of upper airway obstruction in early childhood with the Hall type of SEMD. We therefore suggest that this is a clinically important diagnostic feature of this disorder. Copyright 2007 Wiley-Liss, Inc.

  7. Diagnostic performance of whole-body MRI for the detection of persistent or relapsing disease in multiple myeloma after stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Bannas, Peter; Hentschel, Hannah B.; Bley, Thorsten A.; Derlin, Thorsten; Yamamura, Jin; Adam, Gerhard; Weber, Christoph [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Treszl, Andras; Eulenburg, Christine [University Medical Center Hamburg-Eppendorf, Department of Medical Biometry and Epidemiology, Hamburg (Germany); Stuebig, Thomas; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation, Hamburg (Germany)

    2012-09-15

    To compare the diagnostic performance of whole-body MRI (WBMRI) with haematological parameters for detecting persistent or relapsing disease in patients with multiple myeloma after stem cell transplantation. Sixty-six WBMRI acquisitions were performed in 33 patients with multiple myeloma at two time points after stem cell transplantation. Extent of disease and inter-test dynamics of intra- and extramedullary myeloma manifestations were compared (kappa statistics) with Uniform Response Criteria, comprising haematological parameters. Using data from 66 sequential WBMRI acquisitions in 33 patients, 10 patients (30.3 %) were classified as having progressive disease and 23 (69.7 %) as being in remission. Eight (80 %) of the ten patients with progressive disease revealed intramedullary lesions, and two patients (20 %) had intra- and extramedullary lesions. WBMRI and laboratory tests were concordant in 26/33 (78.8 %) patients. We found an agreement of 51.2 %, 95 % confidence interval 19.8 %-82.6 %, between results from WBMRI and haematological parameters. WBMRI had a sensitivity of 63.6 %, specificity of 86.4 %, PPV of 70.0 %, NPV of 82.6 % and accuracy of 78.8 % for detection of remission. WBMRI allows the detection and exact localisation of intra- and extramedullary myeloma manifestations after stem cell transplantation, but shows only moderate agreement with routinely performed laboratory tests for determination of remission. (orig.)

  8. Importance of the capability for complete resuscitative treatment combining surgery and interventional radiology for potentially lethal multiple injuries: A case report

    Directory of Open Access Journals (Sweden)

    Hiroyuki Otsuka

    2017-10-01

    Conclusions: The capability to perform complete resuscitative treatments that seamlessly combine surgery and interventional radiology in the appropriate order is important for the survival of patients with multiple traumatic injuries.

  9. [REAL-TIME PCR IN THE COMPLEX DIAGNOSTICS OF COMBINED PATHOLOGY OF THE PERIODONTIUM AND GASTRO-DUODENAL ZONE].

    Science.gov (United States)

    Yanushevich, O O; Mayev, I V; Ayvazova, R A; Shibaeva, A V; Shevelev, A B

    2015-01-01

    Biological material of 92 patients (18-85 years old) with different severity chronic periodontitis were analyzed for bacterial pathogen colonization by using Dentofol kit (DNA-technology, Moscow). The cohort included 70 individuals with chronic gastritis, 2 patients with gastric and duodenal ulceration and 20 individuals with no gastric/duodenal pathology. The tight- est association with severity of the chronic periodontitis in the analyzed sub-cohort with the chronic gastritis was found with the prevalence of a complex T. for sythensis/T. denticola. Key contribution of this complex to progression of periodon- titis in males of the eldest group (above 55) was hypothesized. This data essentially differ from published results of other research groups where T. forsythensis and T. denticola were never reported as the principal causative agents of the chronic periodonitis in the gender/age/combined pathology normalized cohorts.

  10. [Added diagnostic benefit of 16-row whole-body spiral CT in patients with multiple trauma differentiated by region and injury severity according to the ATLS concept].

    Science.gov (United States)

    Maurer, M H; Knopke, S; Schröder, R J

    2008-12-01

    To determine the added diagnostic benefit of using MS-CT in multiple trauma patients differentiated by severity of injury and affected body region. A retrospective analysis was performed of the 16-row whole-body spiral CT findings in 275 multiple trauma patients (73 % men, 27 % women; age 39.6 +/- 18.9 years) with regard to additional findings and new findings obtained with CT compared to the findings obtained by conventional projection radiography and abdominal ultrasound in the emergency room. The additional and new findings were differentiated by body region (head, face, chest, pelvis, abdomen, spine) and the degree of severity according to the three classes of injuries distinguished by the ATLS concept (class 1: simple injury, class 2: potentially life threatening, class 3: immediately life threatening). A total of 921 additional findings (= findings potentially relevant for further diagnosis and therapy in addition to the findings obtained by conventional radiography or ultrasound) were obtained by MS-CT in all patients. The distribution by number of patients and body region was as follows: 22 neck, 76 face, 125 chest, 112 abdomen, 50 pelvis, and 91 spine. Most additional findings were categorized as potentially life threatening (ATLS class 2). In addition, there were 439 completely new findings, involving the head in 128 patients (mostly ATLS class 3), the face in 18, the chest in 47, the abdomen in 26, and the spine in 9 patients. Most new findings involving the face, abdomen, and spine were ATLS class 2 injuries. Compared with conventional radiography and ultrasound in the emergency room, 16-row whole-body spiral CT yields numerous additional and new findings in different body regions in patients with multiple traumas. New findings primarily involved the head, and the additional findings involved the chest, pelvis, and spine. Most findings obtained with CT were potentially life threatening (ATLS class 2).

  11. An evaluation of the clinical diagnostic value of contrast-enhanced ultrasound combined with contrast-enhanced computed tomography in space-occupying lesions of the kidney

    Directory of Open Access Journals (Sweden)

    Tian W

    2017-07-01

    Full Text Available Wen Tian,1 Jianbo Lu,2 Dan Jiao,3 Zhibin Cong2 1Department of Blood Transfusion, The Second Hospital of Jilin University, 2Department of Ultrasound, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, 3Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China Background: There are a variety of space-occupying lesions of the kidney, and the benign lesions may be difficult to differentiate from the malignant ones. Therefore, an accurate judgment of the benign and malignant nature of the space-occupying lesions of the kidney is of high importance for the treatment and prognosis of these patients.Objective: To evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS combined with contrast-enhanced computed tomography (CECT in space-occupying lesions of the kidney.Data and methods: Three hundred and sixty-seven patients with space-occupying lesions of the kidney (378 lesions were examined by CEUS and CECT, respectively, then, a combined diagnosis was made after the combination of CEUS and CECT by a multidisciplinary team. The diagnoses from the three methods were compared. The pathological results were taken as the gold standard. The sensitivity, specificity, positive and negative predictive values and area under the receiver operating characteristic (ROC curve were calculated for the three methods. Thus, the diagnostic value of the three methods was assessed.Results: Of the 378 lesions examined, there were 301 malignant lesions and 77 benign lesions. The combined examination revealed 303 malignant lesions, with 9 benign lesions mistakenly diagnosed as malignant ones; thus, the misdiagnosis rate was 11.7%. By using the combined examination, 75 benign lesions were diagnosed, with the missed diagnosis of 7 malignant lesions, so the missed diagnosis rate was 2.3%. The sensitivity, specificity, positive and negative predictive values and area under the ROC

  12. ADMET Evaluation in Drug Discovery. 16. Predicting hERG Blockers by Combining Multiple Pharmacophores and Machine Learning Approaches.

    Science.gov (United States)

    Wang, Shuangquan; Sun, Huiyong; Liu, Hui; Li, Dan; Li, Youyong; Hou, Tingjun

    2016-08-01

    Blockade of human ether-à-go-go related gene (hERG) channel by compounds may lead to drug-induced QT prolongation, arrhythmia, and Torsades de Pointes (TdP), and therefore reliable prediction of hERG liability in the early stages of drug design is quite important to reduce the risk of cardiotoxicity-related attritions in the later development stages. In this study, pharmacophore modeling and machine learning approaches were combined to construct classification models to distinguish hERG active from inactive compounds based on a diverse data set. First, an optimal ensemble of pharmacophore hypotheses that had good capability to differentiate hERG active from inactive compounds was identified by the recursive partitioning (RP) approach. Then, the naive Bayesian classification (NBC) and support vector machine (SVM) approaches were employed to construct classification models by integrating multiple important pharmacophore hypotheses. The integrated classification models showed improved predictive capability over any single pharmacophore hypothesis, suggesting that the broad binding polyspecificity of hERG can only be well characterized by multiple pharmacophores. The best SVM model achieved the prediction accuracies of 84.7% for the training set and 82.1% for the external test set. Notably, the accuracies for the hERG blockers and nonblockers in the test set reached 83.6% and 78.2%, respectively. Analysis of significant pharmacophores helps to understand the multimechanisms of action of hERG blockers. We believe that the combination of pharmacophore modeling and SVM is a powerful strategy to develop reliable theoretical models for the prediction of potential hERG liability.

  13. A combined inspiratory and expiratory muscle training program improves respiratory muscle strength and fatigue in multiple sclerosis.

    Science.gov (United States)

    Ray, Andrew D; Udhoji, Supriya; Mashtare, Terry L; Fisher, Nadine M

    2013-10-01

    To determine the effects of a short-duration, combined (inspiratory and expiratory), progressive resistance respiratory muscle training (RMT) protocol on respiratory muscle strength, fatigue, health-related quality of life, and functional performance in individuals with mild-to-moderate multiple sclerosis (MS). Quasi-experimental before-after trial. University rehabilitation research laboratory. Volunteers with MS (N=21) were divided into 2 groups: RMT (n=11; 9 women, 2 men; mean age ± SD, 50.9 ± 5.7y, mean Expanded Disability Status Scale score ± SD, 3.2 ± 1.9) and a control group that did not train (n=10; 7 women, 3 men; mean age ± SD, 56.2 ± 8.8y, mean Expanded Disability Status Scale score ± SD, 4.4 ± 2.1). Expanded Disability Status Scale scores ranged from 1 to ≤6.5. No patients withdrew from the study. Training was a 5-week combined progressive resistance RMT program, 3d/wk, 30 minutes per session. The primary outcome measures were maximal inspiratory pressure and expiratory pressure and the Modified Fatigue Impact Scale. All subjects completed secondary measures of pulmonary function, the six-minute walk test, the timed stair climb, the Multiple Sclerosis Self-Efficacy Scale, the Medical Outcomes Study 36-Item Short-Form Health Survey, and the Physical Activity Disability Scale. Maximal inspiratory pressure and expiratory pressure (mean ± SD) increased 35% ± 22% (Pfatigue (Modified Fatigue Impact Scale, Pmuscle strength and reduced fatigue in patients with mild to moderate MS. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  14. The use of a novel combination of diagnostic molecular and cytogenetic approaches in horses with sexual karyotype abnormalities: a rare case with an abnormal cellular chimerism.

    Science.gov (United States)

    Demyda-Peyrás, S; Anaya, G; Bugno-Poniewierska, M; Pawlina, K; Membrillo, A; Valera, M; Moreno-Millán, M

    2014-05-01

    Sex chromosome aberrations are known to cause congenital abnormalities and unexplained infertility in horses. Most of these anomalies remain undiagnosed because of the complexity of the horse karyotype and the lack of specialized laboratories that can perform such diagnoses. On the other hand, the utilization of microsatellite markers is a technique widely spread in horse breeding, mostly because of their usage in parentage tests. We studied the usage of a novel combination of diagnostic approaches in the evaluation of a very uncommon case of chromosomal abnormalities in a Spanish purebred colt, primarily detected using a commercial panel of short tandem repeat (STR) makers. Based on these results, we performed a full cytogenetic analysis using conventional and fluorescent in situ hybridization techniques with individual Equus caballus chromosome X and Equus caballus chromosome Y painting probes. We also tested the presence of two genes associated with the sexual development in horses and an extra novel panel of eight microsatellite markers specifically located in the sex chromosome pair. This is the first case report of a leukocyte chimerism between chromosomally normal (64,XY) and abnormal (63,X0) cell lines in horses. Our results indicate that the use of the short tandem repeat markers as a screening technique and as a confirmation utilizing cytogenetic techniques can be used as a very interesting, easy, and nonexpensive diagnostic approach to detect chromosomal abnormalities in the domestic horse. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Chromosomal microarray as a primary diagnostic genomic tool for pregnancies defined as being at increased risk within a population based combined first-trimester screening program

    DEFF Research Database (Denmark)

    Vogel, Ida; Petersen, Olav Bjørn; Christensen, Rikke

    2017-01-01

    OBJECTIVE: To evaluate the impact of using high-resolution chromosomal microarray (CMA) as the standard diagnostic approach to examine for genomic imbalances in pregnancies with increased risk (≥1 in 300) defined through combined first trimester screening (cFTS). METHODS: A cohort of 575...... consecutive pregnancies that had cFTS risk ≥1:300 through a publicly funded population based screening program in the Central and Northern Regions of Denmark between September 2015 and September 2016. Women with an NT ≥3.5 mm or opting for NIPT were excluded. Comparative genomic hybridization was performed...... of aneuploidy were detected as well as 15 (15/575, 2.6%: 95% CI: 1.5-4.3%) cases with a pathogenic or likely pathogenic copy number variant (CNV). Reducing the cFTS risk threshold for invasive diagnostic testing to 1 in 100 or 1 in 50 would have led, respectively, to 60% or 100% of the pathogenic CNVs being...

  16. Combining non selective gas sensors on a mobile robot for identification and mapping of multiple chemical compounds.

    Science.gov (United States)

    Bennetts, Victor Hernandez; Schaffernicht, Erik; Pomareda, Victor; Lilienthal, Achim J; Marco, Santiago; Trincavelli, Marco

    2014-09-17

    In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources.

  17. [An Elderly Patient with Multiple Lung Metastases after Colectomy Successfully Treated with a Combination Oral UFT/LV Chemotherapy Regimen].

    Science.gov (United States)

    Shiraishi, Takehiro; Moriya, Tomoyuki; Ueno, Hideki; Shinto, Eiji; Kajiwara, Yoshiki; Sueyama, Takahiro; Watanabe, Tomoki; Yamadera, Masato; Yamamoto, Junji; Hase, Kazuo

    2016-07-01

    We report an 84-year-old woman with multiple lung metastases from sigmoid colon cancer successfully treated with an oral combination chemotherapeutic agent regimen(UFT/LV).The patient had undergone colectomy for sigmoid colon cancer. Histological examination confirmed a pT4a, pN3, pM1a(LYM), pStage IV tumor.The patient refused adjuvant chemotherapy. However, approximately 9 months postoperatively, she developed a severe cough.Chest radiography and computed tomography(CT)revealed multiple progressive lung metastases.Thereafter, considering her advanced age and general condition, an oral UFT/LV regimen(UFT 300mg/LV 75mg for 7 days every 14 days)was initiated.Two and a half months after initiating chemotherapy, symptom amelioration was observed.Chest radiography and CT showed disappearance of several of the lung metastases, indicating a Partial Response(PR).For the nearly one year to date since diagnosis, she has remained free of cough and the PR has been maintained without chemotherapy-associated adverse events.She is currently being managed on an outpatient basis.The oral UFT/LV regimen is considered to be among the potentially effective and safe treatments for elderly patients with postoperative metastases from colon cancer.

  18. Combined inhibition of p97 and the proteasome causes lethal disruption of the secretory apparatus in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Holger W Auner

    Full Text Available Inhibition of the proteasome is a widely used strategy for treating multiple myeloma that takes advantage of the heavy secretory load that multiple myeloma cells (MMCs have to deal with. Resistance of MMCs to proteasome inhibition has been linked to incomplete disruption of proteasomal endoplasmic-reticulum (ER-associated degradation (ERAD and activation of non-proteasomal protein degradation pathways. The ATPase p97 (VCP/Cdc48 has key roles in mediating both ERAD and non-proteasomal protein degradation and can be targeted pharmacologically by small molecule inhibition. In this study, we compared the effects of p97 inhibition with Eeyarestatin 1 and DBeQ on the secretory apparatus of MMCs with the effects induced by the proteasome inhibitor bortezomib, and the effects caused by combined inhibition of p97 and the proteasome. We found that p97 inhibition elicits cellular responses that are different from those induced by proteasome inhibition, and that the responses differ considerably between MMC lines. Moreover, we found that dual inhibition of both p97 and the proteasome terminally disrupts ER configuration and intracellular protein metabolism in MMCs. Dual inhibition of p97 and the proteasome induced high levels of apoptosis in all of the MMC lines that we analysed, including bortezomib-adapted AMO-1 cells, and was also effective in killing primary MMCs. Only minor toxicity was observed in untransformed and non-secretory cells. Our observations highlight non-redundant roles of p97 and the proteasome in maintaining secretory homeostasis in MMCs and provide a preclinical conceptual framework for dual targeting of p97 and the proteasome as a potential new therapeutic strategy in multiple myeloma.

  19. Diagnostic value of combining heart rate recovery and P-wave changes with exercise-induced changes in the ST segments for prediction of myocardial ischaemia.

    Science.gov (United States)

    Koyuncu, Ilhan; Tuluce, Kamil; Tuluce, Selcen Yakar; Koyuncu, Betul; Eyuboglu, Mehmet; Eyopoglu, Mehmet; Gursul, Erdal; Akcay, Filiz Akyildiz; Safak, Ozgen; Ekinci, Mehmet Akif; Ozdogan, Ozhan; Kozan, Omer

    2015-08-01

    In patients admitted to outpatient clinics with chest pain, changes in the ST-segments of electrocardiogram (ECG) readings are the most widely used criteria during treadmill ECG tests to determine myocardial ischaemia, despite its poor accuracy. In this study, we evaluated the benefit of combining elongation of P-wave duration (Pdur) and abnormal heart rate recovery (HRR) parameters in addition to changes in the ST-segments for the detection of myocardial ischaemia with treadmill ECG testing. Patients (n = 369) with chest pain who underwent both a treadmill ECG test and myocardial perfusion scintigraphy (MPS) were enrolled. P-wave duration was measured at rest and at the end of the first minute of the recovery phase and elongation of the P-wave was calculated. Abnormal HRR was defined as the failure of a decreasing HR at the end of the first minute of the recovery phase >10% of the maximum HR reached during treadmill ECG testing. The sensitivity, specificity, positive and negative predictive values, diagnostic accuracy values, and likelihood ratios (LRs) of changes in the ST-segments, P-wave elongation, abnormal HRR, and the combination of these three variables for predicting myocardial ischaemia detected by MPS, were calculated separately-in patients without previous coronary artery disease (CAD) and in those with CAD. Elongation of Pdur by 20 ms or longer and abnormal HRR during treadmill ECG test were more common in patients with reversible perfusion defects in MPS than in those without perfusion defects (both P < 0.001). When patients were divided into two groups according to the presence or absence of a history of CAD, the addition of elongation of Pdur 20 ms and abnormal HRR to the development of significant changes in the ST-segments detected myocardial ischaemia with 46.7% sensitivity, 97.8% specificity, 67.2% negative predictive value, 88.9% positive predictive value, and 70% diagnostic accuracy in 77 patients with previous CAD. The LR+ of the combination

  20. Assessment of the diagnostic accuracy of double inversion recovery sequence compared with FLAIR and T2W_TSE in detection of cerebral multiple sclerosis lesions.

    Science.gov (United States)

    Abidi, Zahra; Faeghi, Fariborz; Mardanshahi, Zahra; Mortazavi, Hasan

    2017-04-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. MRI has an important role in early diagnosis of MS within diagnostic criteria. To determine the diagnostic value of the double inversion recovery (DIR) sequence in detection of brain MS lesions. In this cross-sectional study, 55 patients were admitted to the MRI department in Vali-E-Asr Hospital in Qaemshahr, Iran, from May 2016 to February 2016. Imaging was performed on a 1.5T Philips MR system using DIR, fluid attenuated inversion recovery (FLAIR), and T2-weighted turbo spin echo (T2W_TSE) sequences with the same parameters, including field of view (FOV), matrix, slice thickness, voxel size, and number of signal averaging (NSA). The DIR sequence has two different time inversions (TI1=3400, TI2=325ms): suppressing cerebrospinal fluid (CSF) and white matter signal. Data analysis was performed using the SPSS version 20, and p-value was gained from the patient-wise analysis by Wilcoxon analysis and paired samples t-test for matched pairs. More lesions in number and size were depicted on the DIR sequence compared with FLAIR (p=0.000 with a relative ratio of 6) and T2W_TSE (p=0.000 with a relative ratio of 10). DIR demonstrated significantly more intracortical lesions compared with FLAIR (p=0.000 with a relative ratio of 2.53) and T2W_TSE (p=0.000 and relative ratio of 8.87). There was significantly higher contrast ratio between the white matter lesions and the normal appearing white matter (NAWM) in all anatomical regions especially in deep white matter (p=0.001). An increasing total number of MS lesions can be detected by DIR sequence; thus, we recommend adding DIR sequence in routine MR protocols for MS patients.

  1. Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: a multidimensional statistical approach.

    Science.gov (United States)

    Südmeyer, Martin; Antke, Christina; Zizek, Tanja; Beu, Markus; Nikolaus, Susanne; Wojtecki, Lars; Schnitzler, Alfons; Müller, Hans-Wilhelm

    2011-05-01

    In vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration and sympathetic cardiac innervation with SPECT is used to distinguish idiopathic Parkinson disease (PD) from atypical parkinsonian disorder (APD). However, the diagnostic accuracy of these imaging approaches as stand-alone procedures is often unsatisfying. The aim of this study was therefore to evaluate to which extent diagnostic accuracy can be increased by their combined use together with a multidimensional statistical algorithm. The SPECT radiotracers (123)I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[1-ethyl-2-pyrrodinyl)-methyl]benzamide (IBZM), (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (FP-CIT), and meta-(123)I-iodobenzylguanidine (MIBG) were used to assess striatal postsynaptic D(2) receptor binding, striatal presynaptic dopamine transporter binding, and myocardial adrenergic innervation, respectively. Thirty-one PD and 17 APD patients were prospectively investigated. PD and APD diagnoses were established using consensus criteria and reevaluated after 37.4 ± 12.4 and 26 ± 11.6 mo in PD and APD, respectively. Test accuracy (TA) for PD-APD differentiation was computed for all logical (Boolean) combinations of imaging modalities by receiver-operating-characteristic analysis--that is, after multidimensional optimization of cutoff values. Analysis showed moderate TA for PD-APD differentiation using each molecular approach alone (IBZM, 79%; MIBG, 73%; and FP-CIT, 73%). For combined use, the highest TA resulted under the assumption that at least 2 of the 3 biologic markers had to be positive for APD using the following cutoff values: 1.46 or less for IBZM, less than 2.10 for FP-CIT, and greater than 1.43 for MIBG. This algorithm distinguished APD from PD with a sensitivity of 94%, specificity of 94% (TA, 94%), positive predictive value of 89%, and negative predictive value of 97%. Results suggest that the multidimensional combination of FP-CIT, IBZM, and MIBG

  2. Diagnostic performance of a combination of Mini-Mental State Examination and Clock Drawing Test in detecting Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Kato Y

    2013-04-01

    Full Text Available Yuka Kato,1 Jin Narumoto,1 Teruyuki Matsuoka,1 Aiko Okamura,1 Hiroyuki Koumi,2 Yusuke Kishikawa,3 Shigenori Terashima,4 Kenji Fukui1 1Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Clinical Psychology, Faculty of Social Welfare, Hanazono University, Kyoto, Japan; 3Misatopia Ogura Hospital, Nagano, Japan; 4Graduate School of Psychology, Kansai University, Osaka, Japan Objective: Because of the growing need for quick cognitive screening tests to distinguish Alzheimer’s disease (AD from mild cognitive impairment (MCI, we compare the diagnostic performance of a combination of the Mini-Mental State Examination (MMSE and a Clock Drawing Test (CDT to the Japanese version of the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-J cog in differentiating between patients with AD, patients with MCI, and healthy controls (HC. Methods: Data from 146 subjects with AD and 60 subjects with MCI, as well as 49 HC, was retrospectively analyzed. We used logistic regression analysis with diagnosis as dependent variables and scores of the MMSE, the CDT-command, and the CDT-copy as independent variables, and receiver operating characteristic analysis to distinguish patients with AD from patients with MCI or HC. Results: When patients with AD were compared to HC, the independent predictors of AD were scores on the MMSE and the CDT-command. This combination was more sensitive than the MMSE alone and has nearly the same sensitivity and specificity as the ADAS-J cog. When patients with AD were compared to patients with MCI, the independent predictors were the MMSE and the CDT-copy. This combination was more sensitive and specific than the MMSE alone and was almost as sensitive and specific as the ADAS-J cog. Conclusion: The combination of the MMSE and the CDT could be a powerful screening tool for differentiating between patients with AD, patients with MCI, and HC. Its

  3. Machine Learning Classification Combining Multiple Features of A Hyper-Network of fMRI Data in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Hao Guo

    2017-11-01

    Full Text Available Exploring functional interactions among various brain regions is helpful for understanding the pathological underpinnings of neurological disorders. Brain networks provide an important representation of those functional interactions, and thus are widely applied in the diagnosis and classification of neurodegenerative diseases. Many mental disorders involve a sharp decline in cognitive ability as a major symptom, which can be caused by abnormal connectivity patterns among several brain regions. However, conventional functional connectivity networks are usually constructed based on pairwise correlations among different brain regions. This approach ignores higher-order relationships, and cannot effectively characterize the high-order interactions of many brain regions working together. Recent neuroscience research suggests that higher-order relationships between brain regions are important for brain network analysis. Hyper-networks have been proposed that can effectively represent the interactions among brain regions. However, this method extracts the local properties of brain regions as features, but ignores the global topology information, which affects the evaluation of network topology and reduces the performance of the classifier. This problem can be compensated by a subgraph feature-based method, but it is not sensitive to change in a single brain region. Considering that both of these feature extraction methods result in the loss of information, we propose a novel machine learning classification method that combines multiple features of a hyper-network based on functional magnetic resonance imaging in Alzheimer's disease. The method combines the brain region features and subgraph features, and then uses a multi-kernel SVM for classification. This retains not only the global topological information, but also the sensitivity to change in a single brain region. To certify the proposed method, 28 normal control subjects and 38 Alzheimer

  4. Machine Learning Classification Combining Multiple Features of A Hyper-Network of fMRI Data in Alzheimer's Disease.

    Science.gov (United States)

    Guo, Hao; Zhang, Fan; Chen, Junjie; Xu, Yong; Xiang, Jie

    2017-01-01

    Exploring functional interactions among various brain regions is helpful for understanding the pathological underpinnings of neurological disorders. Brain networks provide an important representation of those functional interactions, and thus are widely applied in the diagnosis and classification of neurodegenerative diseases. Many mental disorders involve a sharp decline in cognitive ability as a major symptom, which can be caused by abnormal connectivity patterns among several brain regions. However, conventional functional connectivity networks are usually constructed based on pairwise correlations among different brain regions. This approach ignores higher-order relationships, and cannot effectively characterize the high-order interactions of many brain regions working together. Recent neuroscience research suggests that higher-order relationships between brain regions are important for brain network analysis. Hyper-networks have been proposed that can effectively represent the interactions among brain regions. However, this method extracts the local properties of brain regions as features, but ignores the global topology information, which affects the evaluation of network topology and reduces the performance of the classifier. This problem can be compensated by a subgraph feature-based method, but it is not sensitive to change in a single brain region. Considering that both of these feature extraction methods result in the loss of information, we propose a novel machine learning classification method that combines multiple features of a hyper-network based on functional magnetic resonance imaging in Alzheimer's disease. The method combines the brain region features and subgraph features, and then uses a multi-kernel SVM for classification. This retains not only the global topological information, but also the sensitivity to change in a single brain region. To certify the proposed method, 28 normal control subjects and 38 Alzheimer's disease patients were

  5. Retreatment with bortezomib alone or in combination for patients with multiple myeloma following an initial response to bortezomib.

    Science.gov (United States)

    Sood, Raman; Carloss, Harry; Kerr, Robert; Lopez, Jose; Lee, Martin; Druck, Mark; Walters, Ian B; Noga, Stephen J

    2009-10-01

    This clinical trial was conducted to determine the safety and efficacy of bortezomib retreatment in patients with multiple myeloma (MM) who had previously responded to bortezomib. Patients with progressive MM who had previously tolerated bortezomib as a single agent or in combination with other drugs, with a minimum of partial response (PR; >or=50% M-protein reduction) for >or=4 months, who had not received intervening MM therapy, were retreated with bortezomib (days 1, 4, 8, and 11 of a 21-day cycle) with a starting dose being the dose at which the patient ended the initial treatment. Patients were allowed to receive bortezomib on retreatment in combination with dexamethasone, thalidomide, or doxorubicin. Thirty-two patients received bortezomib retreatment (most with added dexamethasone). The median treatment-free interval (last dose of initial bortezomib treatment to first dose of retreatment) was 9.9 (range 2.5-34.0) months. The median duration of retreatment was 2.8 (<1-7.9) months; median total duration of bortezomib treatment was 6.7 (2.5-19.8) months. Based on the investigators' assessment of best response, the overall response rate (complete plus PR) was 50%. The median time from start of retreatment to progressive disease (PD) was 6.6 (95% confidence interval: 5.1-9.6) months. Thirteen patients (41%) experienced PN; bortezomib-related SAEs were reported in four patients. Retreatment with bortezomib alone or in combination is effective and well tolerated in patients with MM who have responded to their initial bortezomib treatment. (c) 2009 Wiley-Liss, Inc.

  6. Combining peak- and chromatogram-based retention time alignment algorithms for multiple chromatography-mass spectrometry datasets

    Directory of Open Access Journals (Sweden)

    Hoffmann Nils

    2012-08-01

    Full Text Available Abstract Background Modern analytical methods in biology and chemistry use separation techniques coupled to sensitive detectors, such as gas chromatography-mass spectrometry (GC-MS and liquid chromatography-mass spectrometry (LC-MS. These hyphenated methods provide high-dimensional data. Comparing such data manually to find corresponding signals is a laborious task, as each experiment usually consists of thousands of individual scans, each containing hundreds or even thousands of distinct signals. In order to allow for successful identification of metabolites or proteins within such data, especially in the context of metabolomics and proteomics, an accurate alignment and matching of corresponding features between two or more experiments is required. Such a matching algorithm should capture fluctuations in the chromatographic system which lead to non-linear distortions on the time axis, as well as systematic changes in recorded intensities. Many different algorithms for the retention time alignment of GC-MS and LC-MS data have been proposed and published, but all of them focus either on aligning previously extracted peak features or on aligning and comparing the complete raw data containing all available features. Results In this paper we introduce two algorithms for retention time alignment of multiple GC-MS datasets: multiple alignment by bidirectional best hits peak assignment and cluster extension (BIPACE and center-star multiple alignment by pairwise partitioned dynamic time warping (CeMAPP-DTW. We show how the similarity-based peak group matching method BIPACE may be used for multiple alignment calculation individually and how it can be used as a preprocessing step for the pairwise alignments performed by CeMAPP-DTW. We evaluate the algorithms individually and in combination on a previously published small GC-MS dataset studying the Leishmania parasite and on a larger GC-MS dataset studying grains of wheat (Triticum aestivum. Conclusions We

  7. Combining peak- and chromatogram-based retention time alignment algorithms for multiple chromatography-mass spectrometry datasets

    Science.gov (United States)

    2012-01-01

    Background Modern analytical methods in biology and chemistry use separation techniques coupled to sensitive detectors, such as gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). These hyphenated methods provide high-dimensional data. Comparing such data manually to find corresponding signals is a laborious task, as each experiment usually consists of thousands of individual scans, each containing hundreds or even thousands of distinct signals. In order to allow for successful identification of metabolites or proteins within such data, especially in the context of metabolomics and proteomics, an accurate alignment and matching of corresponding features between two or more experiments is required. Such a matching algorithm should capture fluctuations in the chromatographic system which lead to non-linear distortions on the time axis, as well as systematic changes in recorded intensities. Many different algorithms for the retention time alignment of GC-MS and LC-MS data have been proposed and published, but all of them focus either on aligning previously extracted peak features or on aligning and comparing the complete raw data containing all available features. Results In this paper we introduce two algorithms for retention time alignment of multiple GC-MS datasets: multiple alignment by bidirectional best hits peak assignment and cluster extension (BIPACE) and center-star multiple alignment by pairwise partitioned dynamic time warping (CeMAPP-DTW). We show how the similarity-based peak group matching method BIPACE may be used for multiple alignment calculation individually and how it can be used as a preprocessing step for the pairwise alignments performed by CeMAPP-DTW. We evaluate the algorithms individually and in combination on a previously published small GC-MS dataset studying the Leishmania parasite and on a larger GC-MS dataset studying grains of wheat (Triticum aestivum). Conclusions We have shown that BIPACE

  8. In vitro activity of mastoparan-AF alone and in combination with clinically used antibiotics against multiple-antibiotic-resistant Escherichia coli isolates from animals.

    Science.gov (United States)

    Lin, Chun-Hsien; Hou, Roger F; Shyu, Ching-Lin; Shia, Wei-Yau; Lin, Chuen-Fu; Tu, Wu-Chun

    2012-07-01

    The in vitro activity of mastoparan-AF, an amphipathic antimicrobial peptide isolated from the hornet venom of Vespa affinis, alone and in combination with various clinically used antibiotics, was investigated against 21 Escherichia coli isolates/strains. Most E. coli isolates tested were detected containing multiple-antimicrobial resistance genes. Antimicrobial activity of mastoparan-AF was measured by MIC, MBC, time-kill kinetic assay and chequerboard titration method. Mastoparan-AF exhibited potent antimicrobial activity against most multiple-antibiotic-resistant E. coli isolates at the concentrations ranging from 4 to 16 μg/ml. Combination studies showed that mastoparan-AF acts synergistically with certain antibiotics, i.e., cephalothin or gentamicin, against some multiple-antibiotic-resistant E. coli isolates. In conclusion, mastoparan-AF alone or in combination with other antibiotics could be promising as alternatives for combating multiple-antibiotic-resistant E. coli in future clinical applications. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Diagnostic value of whole-body low-dose computed tomography (WBLDCT) in bone lesions detection in patients with multiple myeloma (MM)

    Energy Technology Data Exchange (ETDEWEB)

    Ippolito, Davide, E-mail: davide.atena@tiscalinet.it [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Besostri, Valeria, E-mail: valeriabesostri@gmail.com [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Bonaffini, Pietro Andrea, E-mail: pa.bonaffini@gmail.com [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Rossini, Fausto, E-mail: valeriabesostri@hotmail.it [Department of Hematology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Di Lelio, Alessandro, E-mail: valebeso@libero.it [Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Sironi, Sandro, E-mail: sandrosironi@libero.it [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy)

    2013-12-01

    Purpose: To assess the role of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of patients with suspicion of multiple myeloma (MM). Materials and methods: A total of 138 patients (76 male and 62 female; mean age 63.5 years, range 50–81 years), with early MM, underwent WBLDCT protocol study, performed on 16-slice scanner (Brilliance, Philips Medical System, Eindhoven, The Netherlands): tube voltage 120 kV; tube current time product 40 mAs. Diagnosis of osteolytic lesions was performed on the basis of axial and multiplanar reformatted images, whereas the assessment of spinal misalignment and fracture was done by using multiplanar reformatted images. The overall dose delivered to each patient was 4.2 mSv. Every patient gave personal informed consent, as required by our institution guidelines. Results: The diagnosis was established either by histopathology or imaging follow-up (size increase of over a period time). In all 138 patients, image resolution was diagnostic, enabling correct classification of multiple myeloma patients. WBLDCT showed a total of 328 pathologic bone findings in 81/138 patients. CT scanning resulted in complete evaluation of the bone lesions in these areas of the skeleton: skull (42), humerus (15), femur (20), ribs (7), scapulae (13), pelvis (35), clavicle (13), sternum (10), cervical (39), dorsal (65), lombar (48) and sacral rachis (21). In 40/81 bone involvement detected by CT was the only CRAB criterion present. Furthermore, WBLDCT demonstrated pleuro-pulmonary lesions in 20 patients (11 infective, 9 as MM localizations) and 1 renal neoplasia. Conclusion: WBLDCT, detecting bone marrow localizations and demonstrating extra-osseous findings, with a fast scanning time and high resolution images, is a reliable imaging-based tool for a proper management of MM patients.

  10. Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors.

    Science.gov (United States)

    Turner, Joel G; Dawson, Jana L; Grant, Steven; Shain, Kenneth H; Dalton, William S; Dai, Yun; Meads, Mark; Baz, Rachid; Kauffman, Michael; Shacham, Sharon; Sullivan, Daniel M

    2016-08-24

    Acquired drug resistance is the greatest obstacle to the successful treatment of multiple myeloma (MM). Despite recent advanced treatment options such as liposomal formulations, proteasome inhibitors, immunomodulatory drugs, myeloma-targeted antibodies, and histone deacetylase inhibitors, MM is still considered an incurable disease. We investigated whether the clinical exportin 1 (XPO1) inhibitor selinexor (KPT-330), when combined with pegylated liposomal doxorubicin (PLD) or doxorubicin hydrochloride, could overcome acquired drug resistance in multidrug-resistant human MM xenograft tumors, four different multidrug-resistant MM cell lines, or ex vivo MM biopsies from relapsed/refractory patients. Mechanistic studies were performed to assess co-localization of topoisomerase II alpha (TOP2A), DNA damage, and siRNA knockdown of drug targets. Selinexor was found to restore sensitivity of multidrug-resistant 8226B25, 8226Dox6, 8226Dox40, and U266PSR human MM cells to doxorubicin to levels found in parental myeloma cell lines. NOD/SCID-γ mice challenged with drug-resistant or parental U266 human MM and treated with selinexor/PLD had significantly decreased tumor growth and increased survival with minimal toxicity. Selinexor/doxorubicin treatment selectively induced apoptosis in CD138/light-chain-positive MM cells without affecting non-myeloma cells in ex vivo-treated bone marrow aspirates from newly diagnosed or relapsed/refractory MM patients. Selinexor inhibited XPO1-TOP2A protein complexes (proximity ligation assay), preventing nuclear export of TOP2A in both parental and multidrug-resistant MM cell lines. Selinexor/doxorubicin treatment significantly increased DNA damage (comet assay/γ-H2AX) in both parental and drug-resistant MM cells. TOP2A knockdown reversed both the anti-tumor effect and significantly reduced DNA damage induced by selinexor/doxorubicin treatment. The combination of an XPO1 inhibitor and liposomal doxorubicin was highly effective against

  11. Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors

    Directory of Open Access Journals (Sweden)

    Joel G. Turner

    2016-08-01

    Full Text Available Abstract Background Acquired drug resistance is the greatest obstacle to the successful treatment of multiple myeloma (MM. Despite recent advanced treatment options such as liposomal formulations, proteasome inhibitors, immunomodulatory drugs, myeloma-targeted antibodies, and histone deacetylase inhibitors, MM is still considered an incurable disease. Methods We investigated whether the clinical exportin 1 (XPO1 inhibitor selinexor (KPT-330, when combined with pegylated liposomal doxorubicin (PLD or doxorubicin hydrochloride, could overcome acquired drug resistance in multidrug-resistant human MM xenograft tumors, four different multidrug-resistant MM cell lines, or ex vivo MM biopsies from relapsed/refractory patients. Mechanistic studies were performed to assess co-localization of topoisomerase II alpha (TOP2A, DNA damage, and siRNA knockdown of drug targets. Results Selinexor was found to restore sensitivity of multidrug-resistant 8226B25, 8226Dox6, 8226Dox40, and U266PSR human MM cells to doxorubicin to levels found in parental myeloma cell lines. NOD/SCID-γ mice challenged with drug-resistant or parental U266 human MM and treated with selinexor/PLD had significantly decreased tumor growth and increased survival with minimal toxicity. Selinexor/doxorubicin treatment selectively induced apoptosis in CD138/light-chain-positive MM cells without affecting non-myeloma cells in ex vivo-treated bone marrow aspirates from newly diagnosed or relapsed/refractory MM patients. Selinexor inhibited XPO1-TOP2A protein complexes (proximity ligation assay, preventing nuclear export of TOP2A in both parental and multidrug-resistant MM cell lines. Selinexor/doxorubicin treatment significantly increased DNA damage (comet assay/γ-H2AX in both parental and drug-resistant MM cells. TOP2A knockdown reversed both the anti-tumor effect and significantly reduced DNA damage induced by selinexor/doxorubicin treatment. Conclusions The combination of an XPO1 inhibitor

  12. Serum soluble CD26 levels: diagnostic efficiency for atopic dermatitis, cutaneous T-cell lymphoma and psoriasis in combination with serum thymus and activation-regulated chemokine levels.

    Science.gov (United States)

    Miyagaki, T; Sugaya, M; Suga, H; Morimura, S; Kamata, M; Ohmatsu, H; Fujita, H; Asano, Y; Tada, Y; Kadono, T; Sato, S

    2013-01-01

    CD26 is a multifunctional type II transmembrane glycoprotein, which also exists as a secreted isoform, soluble CD26 (sCD26). The CD26 expression on circulating T cells is decreased in some skin diseases such as cutaneous T-cell lymphoma (CTCL) and psoriasis. It remains to be determined whether sCD26 can be used as a marker of skin diseases or not. To investigate utility of sCD26 as a diagnostic marker of skin diseases in combination with thymus and activation-regulated chemokine (TARC). Serum sCD26 levels were measured using enzyme-linked immunosorbent assay in 130 participants including 32 patients with atopic dermatitis (AD); 45 patients with CTCL; 26 patients with psoriasis; and 27 healthy controls. Serum sCD26 levels in patients with CTCL and psoriasis (162.1 ± 80.2 ng/mL and 125.4 ± 82.1 ng/mL respectively) were significantly lower than those of healthy controls (392.6 ± 198.7 ng/mL; P psoriasis were 65.2-73.7%, 81.4-97.6%, 65.2-94.4%, and 81.4-88.9% respectively. Serum sCD26 levels, combined with serum TARC levels, are helpful in diagnosis of AD, CTCL and psoriasis. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

  13. Biochemical markers of vitamin B12 deficiency combined in one diagnostic parameter: the age-dependence and association with cognitive function and blood hemoglobin.

    Science.gov (United States)

    Fedosov, Sergey N

    2013-06-25

    Vitamin B12 deficiency is diagnosed by measurements of total B12, holo-transcobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (Hcy) in blood. Results of the individual biochemical tests are often contradictory. Here the four markers are combined to achieve a more reliable indication of the B12 status. The results are aligned with hemoglobin and cognitive score. Databases from the literature were plotted in coordinates x=(holoTC·B12)(1∕2), y=1∕2·log10(MMA·Hcy), where distribution of points revealed the subgroups characterized by logarithmic ratios lr=log10[(holoTC·B12)/(MMA·Hcy)]. Distance between the subgroups w=lr(Test)-lr(Normal) was taken as a robust biochemical indicator of B12 status ("wellness parameter"). The dependence of lr(Normal) vs. age was described by a mathematical function to correct parameter w. The B12 status was defined as "excellent" (w≈+0.4), "normal" (w≈0), "transitional" (w≈-0.5), "deficient" (w≈-1.7) and "pernicious" (w≈-3.0). The groups of individuals with either w≥0 or w≤-1 exhibited the statistically significant differences in both hemoglobin and cognitive score. Analogous assessment of B12 status by the individual markers agreed with only one out of two physiological characteristics. Combined parameter w is a reliable diagnostic tool. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Combined proximal tubulopathy, crystal-storing histiocytosis, and cast nephropathy in a patient with light chain multiple myeloma.

    Science.gov (United States)

    Wu, Chung-Kuan; Yang, An-Hang; Lai, Hung-Chih; Lin, Bing-Shi

    2017-05-25

    The diagnosis of myeloma, a plasma dyscrasia, often results from the workup of unexplained renal disease. Persistent renal failure in myeloma is commonly caused by tubular nephropathy due to circulating immunoglobulins and free light chains. Myeloma cast nephropathy is characterized by crystalline precipitates of monoclonal light chains within distal tubules. Immunoglobulin crystallization rarely occurs intracellularly, within proximal tubular cells (light chain proximal tubulopathy) and interstitial histiocytes (crystal-storing histiocytosis). We present a case report of a rare simultaneous occurrence of light chain proximal tubulopathy, crystal-storing histiocytosis, and myeloma cast nephropathy in a patient with κ light chain multiple myeloma. A 48-years-old man presented with uremia and anemia. Laboratory examination revealed low levels of serum IgG, IgA, and IgM. Serum and urine immunofixation electrophoresis showed a free κ monoclonal band. Bone marrow aspiration and biopsy revealed hypercellularity with marked plasmacytosis. Light microscopy revealed eosinophilic cuboid- and rhomboid-shaped crystals in the cytoplasm of proximal tubular epithelial cells, diffuse large mononuclear and multinuclear cells in the interstitium, and obstructed distal tubules with cast and giant cell reaction. Immunohistochemical examination indicated intense staining for κ light chains within casts, histiocytes, and tubular epithelial cells. Electron microscopy revealed electro-dense cuboid-, rhomboid-, or needle-shaped crystalline inclusions in proximal tubular epithelial cells and interstitial histiocytes. According to these results, we confirmed that this patient with myeloma exhibited simultaneous light chain proximal tubulopathy, crystal-storing histiocytosis, and myeloma cast nephropathy, which were attributed to monoclonal κ light chains. In addition to dialysis, the patient received induction chemotherapy with a combination of bortezomib, cyclophosphamide, and

  15. Co-existence of Blau syndrome and NAID? Diagnostic challenges associated with presence of multiple pathogenic variants in NOD2 gene: a case report.

    Science.gov (United States)

    Dziedzic, Magdalena; Marjańska, Agata; Bąbol-Pokora, Katarzyna; Urbańczyk, Anna; Grześk, Elżbieta; Młynarski, Wojciech; Kołtan, Sylwia

    2017-07-27

    Pediatric autoinflammatory diseases are rare and still poorly understood conditions resulting from defective genetic control of innate immune system, inter alia from anomalies of NOD2 gene. The product of this gene is Nod2 protein, taking part in maintenance of immune homeostasis. Clinical form of resultant autoinflammatory condition depends on NOD2 genotype; usually patients with NOD2 defects present with Blau syndrome, NOD2-associated autoinflammatory disease (NAID) or Crohn's disease. We present the case of a 7-year-old girl with co-existing symptoms of two rare diseases, Blau syndrome and NAID. Overlapping manifestations of two syndromes raised a significant diagnostic challenge, until next-generation molecular test (NGS) identified presence of three pathogenic variants of NOD2 gene: P268S, IVS8+158, 1007 fs, and established the ultimate diagnosis. Presence of multiple genetical abnormalities resulted in an ambiguous clinical presentation with overlapping symptoms of Blau syndrome and NAID. Final diagnosis of autoinflammatory disease opened new therapeutic possibilities, including the use of biological treatments.

  16. [Diagnostic value of combining serum soluble ST2 and interleukin-33 for heart failure patients with preserved left ventricular ejection fraction].

    Science.gov (United States)

    Luo, N S; Zhang, H F; Liu, P M; Lin, Y Q; Huang, T C; Yang, Y; Wang, J F

    2017-03-24

    Objective: Diagnostic efficacy of serum markers is low for heart failure patients with preserved left ventricular ejection fraction (HF-pEF) as compared to heart failure patients with reduced left ventricular ejection fraction.We sought to explore the diagnostic value of serum levels of soluble ST2 (sST2) combined with interleukin-33 (IL-33) for the diagnosis of HF-pEF in this study. Methods: A total of 376 patients with HF-pEF (HF group), 376 matched-control patients without heart failure who shared similar clinical characteristics (non-HF group) were included in the study.Another 500 healthy individuals were recruited for assessing the normal ranges of IL-33 and sST2.Serum levels of NT-proBNP were measured by chemi-luminescence assay, while IL-33 and sST2 were measured by enzyme linked immunosorbent assay. Results: Serum levels of IL-33 and sST2 were not normally distributed in healthy population.Serum concentrations of IL-33 and sST2 were significantly higher in HF-pEF patients than in patients in non-HF group (median, IL-33: 0.437 μg/L vs. 0.127 μg/L, P pEF was 0.763 (95% CI 0.729-0.795, P pEF was 0.83, with 74.73% sensitivity and 84.57% specificity.The AUC of sST2 for detecting HF-pEF was significantly higher than NT-proBNP in population with high serum IL-33 (AUC: 0.88 vs. 0.83, P pEF diagnosis, especially for patients with high serum IL-33 concentrations.

  17. Discordance rate, a new concept for combining diagnostic decisions with analytical performance characteristics. 1. Application in method or sample system comparisons and in defining decision limits.

    Science.gov (United States)

    Haeckel, Rainer; Wosniok, Werner; Puentmann, Isabel

    2003-03-01

    Method comparison studies are usually evaluated by several statistical tests (e.g., regression analysis) which sufficiently describe the analytical (dis)agreement between the results of two procedures. However, they do not provide any information how differences, if observed, influence diagnostic decision making. A novel statistical approach is described to test the clinical relevance of differences between two analytical procedures. The new procedure requires a population-based probability which describes the distribution of values within the population under study and an analytical probability quantifying the risk of errors due to replacing one method by the other. The population probability was derived from 171 subjects from two outpatient departments (internal medicine and dermatology) who were subjected to an oral glucose tolerance test because type 2 diabetes mellitus was suspected. The analytical probability was determined from duplicate glucose measurements in venous and capillary blood, and venous plasma in the fasting and 2 h post-challenge state by the routine method used in a central laboratory (Ebio analyzer) and a (POCT) glucometer (Elite). The two probabilities were combined into one "error rate" (discordance rate). The new concept was applied to three examples. In the first example, a comparison between two analytical systems led to discordance rates above 15%. After transforming the Elite analyzer results by a regression function, the discordance rate decreased below 5%, which was considered to be acceptable for the diagnostic purpose studied. In the second example, discordance rates were estimated by comparing different sample systems with each other. The use of whole blood in comparison with venous plasma led to discordance rates of 5-7% for venous blood and 7-10% for capillary blood. The same data set was also used in a third example to derive decision limits for capillary and venous blood from the established plasma values. The proposed

  18. Diagnostic value of combining {sup 11}C-choline and {sup 18}F-FDG PET/CT in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Castilla-Lievre, Maria-Angela [University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Department of Nuclear Medicine, Hopital Antoine Beclere, Clamart (France); IMIV - UMR 1023 Inserm/CEA/Universite Paris Sud - ERL 9218 CNRS, Orsay (France); Franco, Dominique [Universite Paris-Sud, Department of Surgery, Hopital Antoine Beclere, University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Clamart (France); Gervais, Philippe; Kuhnast, Bertrand; Desarnaud, Serge; Helal, Badia-Ourkia [IMIV - UMR 1023 Inserm/CEA/Universite Paris Sud - ERL 9218 CNRS, Orsay (France); CEA, DSV, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Agostini, Helene [University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Clinical Research Unit of Hopitaux universitaires Paris-Sud, Hopital Kremlin Bicetre (France); Marthey, Lysiane [Universite Paris-Sud, Department of Gastroenterology, Hopital Antoine Beclere, University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Clamart (France)

    2016-05-15

    In this prospective study, our goal was to emphasize the diagnostic value of combining {sup 11}C-choline and {sup 18}F-FDG PET/CT for hepatocellular carcinoma (HCC) in patients with chronic liver disease. Thirty-three consecutive patients were enrolled. All patients were suspected to have HCC based on CT and/or MRI imaging. A final diagnosis was obtained by histopathological examination or by imaging alone according to American Association for the Study of Liver Disease criteria. All patients underwent PET/CT with both tracers within a median of 5 days. All lesions showing higher tracer uptake than normal liver were considered positive for HCC. We examined how tracer uptake was related to biological (serum α-fetoprotein levels) and pathological (differentiation status, peritumoral capsule and vascular invasion) prognostic markers of HCC, as well as clinical observations at 6 months (recurrence and death). Twenty-eight HCC, four cholangiocarcinomas and one adenoma were diagnosed. In the HCC patients, the sensitivity of {sup 11}C-choline, {sup 18}F-FDG and combined {sup 11}C-choline and {sup 18}F-FDG PET/CT for the detection of HCC was 75 %, 36 % and 93 %, respectively. Serum α-fetoprotein levels >200 ng/ml were more frequent among patients with {sup 18}F-FDG-positive lesions than those with {sup 18}F-FDG-negative lesions (p < 0.05). Early recurrence (n=2) or early death (n=5) occurred more frequently in patients with {sup 18}F-FDG-positive lesions than in those with {sup 18}F-FDG-negative lesions (p < 0.05). The combined use of {sup 11}C-choline and {sup 18}F-FDG PET/CT detected HCC with high sensitivity. This approach appears to be of potential prognostic value and may facilitate the selection of patients for surgical resection or liver transplantation. (orig.)

  19. Using Meta-Analysis to Inform the Design of Subsequent Studies of Diagnostic Test Accuracy

    Science.gov (United States)

    Hinchliffe, Sally R.; Crowther, Michael J.; Phillips, Robert S.; Sutton, Alex J.

    2013-01-01

    An individual diagnostic accuracy study rarely provides enough information to make conclusive recommendations about the accuracy of a diagnostic test; particularly when the study is small. Meta-analysis methods provide a way of combining information from multiple studies, reducing uncertainty in the result and hopefully providing substantial…

  20. Targeted Antibiotic Prophylaxis for Lung Transplantation in Cystic Fibrosis Patients Colonised with Pseudomonas aeruginosa Using Multiple Combination Bactericidal Testing

    Directory of Open Access Journals (Sweden)

    Helmy Haja Mydin

    2012-01-01

    Full Text Available Early infection is a recognised complication after lung transplantation in patients with cystic fibrosis (CF. Our centre uses multiple combination bactericidal testing (MCBT when determining appropriate peritransplant prophylactic regimens. To evaluate our strategy, we compared the incidence of posttransplant infection in patients whose peritransplant antimicrobial regimens were determined using MCBT versus standard sensitivity testing. Patients with CF who were infected with Pseudomonas aeruginosa and underwent lung transplantations between 2000 and 2010 were included. Data was collected from clinical records and our microbiology database. Microorganisms cultured were mapped against antibiotic resistance, method of sensitivity testing, and antibiotics administered peritransplant. 129 patients were identified (mean age 28, male : female, 63 : 66. Fifty patients (38.8% had antibiotics determined by MCBT. Two patients in the MCBT group developed septicaemia, 13 in the conventional group (P≤0.05, 2-tailed Fisher's test. Sepsis was attributable to P. aeruginosa in one patient from the MCBT group and seven patients in the conventional group (P=0.15. P. aeruginosa was recovered from the posttransplant pleural fluid of one patient who received MCBT-guided prophylaxis, six patients in the conventional group (P=0.25. Patients given antibiotics based on MCBT had significantly lower rates of septicaemia and lower rates of empyema.

  1. Multiple trait model combining random regressions for daily feed intake with single measured performance traits of growing pigs

    Directory of Open Access Journals (Sweden)

    Künzi Niklaus

    2002-01-01

    Full Text Available Abstract A random regression model for daily feed intake and a conventional multiple trait animal model for the four traits average daily gain on test (ADG, feed conversion ratio (FCR, carcass lean content and meat quality index were combined to analyse data from 1 449 castrated male Large White pigs performance tested in two French central testing stations in 1997. Group housed pigs fed ad libitum with electronic feed dispensers were tested from 35 to 100 kg live body weight. A quadratic polynomial in days on test was used as a regression function for weekly means of daily feed intake and to escribe its residual variance. The same fixed (batch and random (additive genetic, pen and individual permanent environmental effects were used for regression coefficients of feed intake and single measured traits. Variance components were estimated by means of a Bayesian analysis using Gibbs sampling. Four Gibbs chains were run for 550 000 rounds each, from which 50 000 rounds were discarded from the burn-in period. Estimates of posterior means of covariance matrices were calculated from the remaining two million samples. Low heritabilities of linear and quadratic regression coefficients and their unfavourable genetic correlations with other performance traits reveal that altering the shape of the feed intake curve by direct or indirect selection is difficult.

  2. Retrievals of Surface Air Temperature Using Multiple Satellite Data Combinations over Complex Terrain in the Korean Peninsula

    Science.gov (United States)

    Jang, K.; Won, M.; Yoon, S.; Lim, J.

    2016-12-01

    Surface air temperature (Tair) is a fundamental factor for terrestrial environments and plays a major role in the fields of applied meteorology, climatology, and ecology. The satellite remotely sensed data offers the opportunity to estimate Tair on the earth's surface with high spatial and temporal resolutions. The Moderate Resolution Imaging Spectroradiometer (MODIS) provides effective Tair retrievals although restricted to clear sky condition. MODIS Tair over complex terrain can result in significant retrieval errors due to the retrieval height mismatch to the elevation of local weather stations. In this study, we propose the methodology to estimate Tair over complex terrain for all sky conditions using multiple satellite data fusion based on the pixel-wise regression method. The combination of synergistic information from MODIS Tair and the brightness temperature (Tb) retrievals at 37 GHz frequency from the satellite microwave sensor were used for analysis. The air temperature lapse rate was applied to estimate the near-surface Tair considering the complex terrain such as mountainous regions. The retrieval results produced from this study showed a good agreement (RMSE Administration (KMA). The gaps in the MODIS Tair data due to cloud contamination were successfully filled using the proposed method which yielded similar accuracy as retrievals of clear sky. The results of this study indicate that the satellite data fusion can continuously produce Tair retrievals with reasonable accuracy and that the application of the temperature lapse rate can lead to improvement of the reliability over complex terrains such as the Korean Peninsula.

  3. Multiple Cross Displacement Amplification Combined with Gold Nanoparticle-Based Lateral Flow Biosensor for Detection of Vibrio parahaemolyticus.

    Science.gov (United States)

    Wang, Yi; Li, Hui; Li, Dongxun; Li, Kewei; Wang, Yan; Xu, Jianguo; Ye, Changyun

    2016-01-01

    Vibrio parahaemolyticus (V. parahaemolyticus) is a marine seafood-borne pathogen causing severe illnesses in humans and aquatic animals. In the present study, multiple cross displacement amplification was combined with a lateral flow biosensor (MCDA-LFB) to detect the toxR gene of V. parahaemolyticus in DNA extracts from pure cultures and spiked oyster homogenates. Amplification was carried out at a constant temperature (62°C) for only 30 min, and amplification products were directly applied to the biosensor. The entire process, including oyster homogenate processing (30 min), isothermal amplification (30 min) and results indicating (∼2 min), could be completed within 65 min. Amplification product was detectable from as little as 10 fg of pure V. parahaemolyticus DNA and from approximately 4.2 × 10(2) CFU in 1 mL of oyster homogenate. No cross-reaction with other Vibrio species and with non-Vibrio species was observed. Therefore, the MCDA-LFB method established in the current report is suitable for the rapid screening of V. parahaemolyticus in clinical, food, and environmental samples.

  4. LENALIDOMIDE IN COMBINATION WITH DEXAMETHASONE IN ELDERLY PATIENTS WITH ADVANCED, RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2013-06-01

    Full Text Available Salvage therapy of elderly patients with advanced, relapsed and refractory multiple myeloma (MM is often limited by poor marrow reserve and multi-organ impairment. In particular, renal failure occurs in up to 50% of such patients, an this can potentially limit the therapeutic options. Both thalidomide and bortezomib have proven effective in these patients, with an acceptable toxicity, while, in clinical practice, lenalidomide is generally not considered a first-choice drug for MM patients with renal failure as early reports showed an increased hematological toxicity unless appropriate dose reduction is applied. Aim of this study was a retrospective evaluation of the efficacy of the combination Lenalidomide +Dexamethasone in a population of elderly MM patients treated in 5 Italian Centers. The study included 20 consecutive MM patients (9 M, 11 F, median age 76.5 years with relapsed (N= 6 or refractory (N=13 MM and moderate to severe renal failure, defined as creatinine clearance (Cr Cl partial response was observed in 8 patients (40%, 1 of whom obtained a VGPR; 4 additional patients achieved a minor response. Median response duration was 16 months (range 2-19+ months. A complete and partial renal response was obtained in 4 and 3 patients, respectively, all of them were responsive to Lenalidomide-dexamethasone According to our data, LEN+DEX has shown efficacy and acceptable toxicity in this population of elderly patients with advanced MM and renal failure

  5. Composition dependent multiple structural transformations of myoglobin in aqueous ethanol solution: A combined experimental and theoretical study

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, R.; Samajdar, R. N.; Bhattacharyya, Aninda Jiban; Bagchi, B., E-mail: bbagchi@sscu.iisc.ernet.in [Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012 (India)

    2015-07-07

    Experimental studies (circular dichroism and ultra-violet (UV) absorption spectra) and large scale atomistic molecular dynamics simulations (accompanied by order parameter analyses) are combined to establish a number of remarkable (and unforeseen) structural transformations of protein myoglobin in aqueous ethanol mixture at various ethanol concentrations. The following results are particularly striking. (1) Two well-defined structural regimes, one at x{sub EtOH} ∼ 0.05 and the other at x{sub EtOH} ∼ 0.25, characterized by formation of distinct partially folded conformations and separated by a unique partially unfolded intermediate state at x{sub EtOH} ∼ 0.15, are identified. (2) Existence of non-monotonic composition dependence of (i) radius of gyration, (ii) long range contact order, (iii) residue specific solvent accessible surface area of tryptophan, and (iv) circular dichroism spectra and UV-absorption peaks are observed. Interestingly at x{sub EtOH} ∼ 0.15, time averaged value of the contact order parameter of the protein reaches a minimum, implying that this conformational state can be identified as a molten globule state. Multiple structural transformations well known in water-ethanol binary mixture appear to have considerably stronger effects on conformation and dynamics of the protein. We compare the present results with studies in water-dimethyl sulfoxide mixture where also distinct structural transformations are observed along with variation of co-solvent composition.

  6. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    Science.gov (United States)

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs.

  7. Composition dependent multiple structural transformations of myoglobin in aqueous ethanol solution: A combined experimental and theoretical study

    Science.gov (United States)

    Ghosh, R.; Samajdar, R. N.; Bhattacharyya, Aninda Jiban; Bagchi, B.

    2015-07-01

    Experimental studies (circular dichroism and ultra-violet (UV) absorption spectra) and large scale atomistic molecular dynamics simulations (accompanied by order parameter analyses) are combined to establish a number of remarkable (and unforeseen) structural transformations of protein myoglobin in aqueous ethanol mixture at various ethanol concentrations. The following results are particularly striking. (1) Two well-defined structural regimes, one at xEtOH ˜ 0.05 and the other at xEtOH ˜ 0.25, characterized by formation of distinct partially folded conformations and separated by a unique partially unfolded intermediate state at xEtOH ˜ 0.15, are identified. (2) Existence of non-monotonic composition dependence of (i) radius of gyration, (ii) long range contact order, (iii) residue specific solvent accessible surface area of tryptophan, and (iv) circular dichroism spectra and UV-absorption peaks are observed. Interestingly at xEtOH ˜ 0.15, time averaged value of the contact order parameter of the protein reaches a minimum, implying that this conformational state can be identified as a molten globule state. Multiple structural transformations well known in water-ethanol binary mixture appear to have considerably stronger effects on conformation and dynamics of the protein. We compare the present results with studies in water-dimethyl sulfoxide mixture where also distinct structural transformations are observed along with variation of co-solvent composition.

  8. Combining interactive multiple goal linear programming with an inter-stakeholder communication matrix to generate land use options

    NARCIS (Netherlands)

    Nidumolu, U.B.; Keulen, van H.; Lubbers, M.T.M.H.; Mapfumo, P.

    2007-01-01

    An Interactive Multiple Goal Linear Programming (IMGLP) model is developed that considers objectives of multiple stakeholders, i.e. different farmer groups, district agricultural officers and agricultural scientists for agricultural land use analysis. The analysis focuses on crop selection;

  9. Introduction of a New Diagnostic Method for Breast Cancer Based on Fine Needle Aspiration (FNA) Test Data and Combining Intelligent Systems

    Science.gov (United States)

    Fiuzy, Mohammad; Haddadnia, Javad; Mollania, Nasrin; Hashemian, Maryam; Hassanpour, Kazem

    2012-01-01

    Background Accurate Diagnosis of Breast Cancer is of prime importance. Fine Needle Aspiration test or "FNA”, which has been used for several years in Europe, is a simple, inexpensive, noninvasive and accurate technique for detecting breast cancer. Expending the suitable features of the Fine Needle Aspiration results is the most important diagnostic problem in early stages of breast cancer. In this study, we introduced a new algorithm that can detect breast cancer based on combining artificial intelligent system and Fine Needle Aspiration (FNA). Methods We studied the Features of Wisconsin Data Base Cancer which contained about 569 FNA test samples (212 patient samples (malignant) and 357 healthy samples (benign)). In this research, we combined Artificial Intelligence Approaches, such as Evolutionary Algorithm (EA) with Genetic Algorithm (GA), and also used Exact Classifier Systems (here by Fuzzy C-Means (FCM)) to separate malignant from benign samples. Furthermore, we examined artificial Neural Networks (NN) to identify the model and structure. This research proposed a new algorithm for an accurate diagnosis of breast cancer. Results According to Wisconsin Data Base Cancer (WDBC) data base, 62.75% of samples were benign, and 37.25% were malignant. After applying the proposed algorithm, we achieved high detection accuracy of about "96.579%” on 205 patients who were diagnosed as having breast cancer. It was found that the method had 93% sensitivity, 73% specialty, 65% positive predictive value, and 95% negative predictive value, respectively. If done by experts, Fine Needle Aspiration (FNA) can be a reliable replacement for open biopsy in palpable breast masses. Evaluation of FNA samples during aspiration can decrease insufficient samples. FNA can be the first line of diagnosis in women with breast masses, at least in deprived regions, and may increase health standards and clinical supervision of patients. Conclusion Such a smart, economical, non-invasive, rapid

  10. Introduction of a New Diagnostic Method for Breast Cancer Based on Fine Needle Aspiration (FNA) Test Data and Combining Intelligent Systems.

    Science.gov (United States)

    Fiuzy, Mohammad; Haddadnia, Javad; Mollania, Nasrin; Hashemian, Maryam; Hassanpour, Kazem

    2012-01-01

    Accurate Diagnosis of Breast Cancer is of prime importance. Fine Needle Aspiration test or "FNA", which has been used for several years in Europe, is a simple, inexpensive, noninvasive and accurate technique for detecting breast cancer. Expending the suitable features of the Fine Needle Aspiration results is the most important diagnostic problem in early stages of breast cancer. In this study, we introduced a new algorithm that can detect breast cancer based on combining artificial intelligent system and Fine Needle Aspiration (FNA). We studied the Features of Wisconsin Data Base Cancer which contained about 569 FNA test samples (212 patient samples (malignant) and 357 healthy samples (benign)). In this research, we combined Artificial Intelligence Approaches, such as Evolutionary Algorithm (EA) with Genetic Algorithm (GA), and also used Exact Classifier Systems (here by Fuzzy C-Means (FCM)) to separate malignant from benign samples. Furthermore, we examined artificial Neural Networks (NN) to identify the model and structure. This research proposed a new algorithm for an accurate diagnosis of breast cancer. According to Wisconsin Data Base Cancer (WDBC) data base, 62.75% of samples were benign, and 37.25% were malignant. After applying the proposed algorithm, we achieved high detection accuracy of about "96.579%" on 205 patients who were diagnosed as having breast cancer. It was found that the method had 93% sensitivity, 73% specialty, 65% positive predictive value, and 95% negative predictive value, respectively. If done by experts, Fine Needle Aspiration (FNA) can be a reliable replacement for open biopsy in palpable breast masses. Evaluation of FNA samples during aspiration can decrease insufficient samples. FNA can be the first line of diagnosis in women with breast masses, at least in deprived regions, and may increase health standards and clinical supervision of patients. Such a smart, economical, non-invasive, rapid and accurate system can be introduced as a

  11. Multiplexed analysis combining distinctly-sized CdTe-MPA quantum dots and chemometrics for multiple mutually interfering analyte determination.

    Science.gov (United States)

    Bittar, Dayana B; Ribeiro, David S M; Páscoa, Ricardo N M J; Soares, José X; Rodrigues, S Sofia M; Castro, Rafael C; Pezza, Leonardo; Pezza, Helena R; Santos, João L M

    2017-11-01

    Semiconductor quantum dots (QDs) have demonstrated a great potential as fluorescent probes for heavy metals monitoring. However, their great reactivity, whose tunability could be difficult to attain, could impair selectivity yielding analytical results with poor accuracy. In this work, the combination in the same analysis of multiple QDs, each with a particular ability to interact with the analyte, assured a multi-point detection that was not only exploited for a more precise analyte discrimination but also for the simultaneous discrimination of multiple mutually interfering species, in the same sample. Three different MPA-CdTe QDs (2.5, 3.0 and 3.8nm) with a good size distribution, confirmed by the FWHM values of 48.6, 55.4 and 80.8nm, respectively, were used. Principal component analysis (PCA) and partial least squares regression (PLS) were used for fluorescence data analysis. Mixtures of two MPA-CdTe QDs, emitting at different wavelength namely 549/566, 549/634 and 566/634nm were assayed. The 549/634nm emitting QDs mixture provided the best results for the discrimination of distinct ions on binary and ternary mixtures. The obtained RMSECV and R(2)CV values for the binary mixture were good, namely, from 0.01 to 0.08mgL(-1) and from 0.74 to 0.89, respectively. Regarding the ternary mixture the RMSECV and R(2)CV values were good for Hg(II) (0.06 and 0.73mgL(-1), respectively) and Pb(II) (0.08 and 0.87mg L(-1), respectively) and acceptable for Cu(II) (0.02 and 0.51mgL(-1), respectively). In conclusion, the obtained results showed that the developed approach is capable of resolve binary and ternary mixtures of Pb (II), Hg (II) and Cu (II), providing accurate information about lead (II) and mercury (II) concentration and signaling the occurrence of Cu (II). Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Metagenomic diagnostics for the simultaneous detection of multiple pathogens in human stool specimens from Côte d'Ivoire: a proof-of-concept study.

    Science.gov (United States)

    Schneeberger, Pierre H H; Becker, Sören L; Pothier, Joël F; Duffy, Brion; N'Goran, Eliézer K; Beuret, Christian; Frey, Jürg E; Utzinger, Jürg

    2016-06-01

    The intestinal microbiome is a complex community and its role in influencing human health is poorly understood. While conventional microbiology commonly attributes digestive disorders to a single microorganism, a metagenomic approach can detect multiple pathogens simultaneously and might elucidate the role of microbial communities in the pathogenesis of intestinal diseases. We present a proof-of-concept that a shotgun metagenomic approach provides useful information on the diverse composition of intestinal pathogens and antimicrobial resistance profiles in human stool samples. In October 2012, we obtained stool specimens from patients with persistent diarrhea in south Côte d'Ivoire. Four stool samples were purposefully selected and subjected to microscopy, multiplex polymerase chain reaction (PCR), and a metagenomic approach. For the latter, we employed the National Center for Biotechnology Information nucleotide database and screened for 36 pathogenic organisms (bacteria, helminths, intestinal protozoa, and viruses) that may cause digestive disorders. We further characterized the bacterial population and the prevailing resistance patterns by comparing our metagenomic datasets with a genome-specific marker database and with a comprehensive antibiotic resistance database. In the four patients, the metagenomic approach identified between eight and 11 pathogen classes that potentially cause digestive disorders. For bacterial pathogens, the diagnostic agreement between multiplex PCR and metagenomics was high; yet, metagenomics diagnosed several bacteria not detected by multiplex PCR. In contrast, some of the helminth and intestinal protozoa infections detected by microscopy were missed by metagenomics. The antimicrobial resistance analysis revealed the presence of genes conferring resistance to several commonly used antibiotics. A metagenomic approach provides detailed information on the presence and diversity of pathogenic organisms in human stool samples

  13. Clinical outcomes of combined flow-pressure drop measurements using newly developed diagnostic endpoint: Pressure drop coefficient in patients with coronary artery dysfunction

    Science.gov (United States)

    Effat, Mohamed A; Peelukhana, Srikara Viswanath; Banerjee, Rupak K

    2016-01-01

    AIM: To combine pressure and flow parameter, pressure drop coefficient (CDP) will result in better clinical outcomes in comparison to the fractional flow reserve (FFR) group. METHODS: To test this hypothesis, a comparison was made between the FFR 27.9 groups in this study, for the major adverse cardiac events [major adverse cardiac events (MACE): Primary outcome] and patients’ quality of life (secondary outcome). Further, a comparison was also made between the survival curves for the FFR 27.9 groups. Two-tailed χ2 test proportions were performed for the comparison of primary and secondary outcomes. Kaplan-Meier survival analysis was performed to compare the survival curves of FFR 27.9 groups (MedcalcV10.2, Mariakerke, Belgium). Results were considered statistically significant for P 27.9 group (8.57%, 2 out of 35). Noteworthy is the reduction in the %MACE in the CDP > 27.9 group, in comparison to the FFR 27.9 groups. Survival analysis results suggest that the survival time for the CDP > 27.9 group (n = 35) is significantly higher (P = 0.048) in comparison to the survival time for the FFR < 0.75 group (n = 20). The results remained similar for a FFR = 0.80 cut-off. CONCLUSION: Based on the above, CDP could prove to be a better diagnostic end-point for clinical revascularization decision-making in the cardiac catheterization laboratories. PMID:27022460

  14. Multiple nanoemulsion system for an oral combinational delivery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation.

    Science.gov (United States)

    Pangeni, Rudra; Choi, Sang Won; Jeon, Ok-Cheol; Byun, Youngro; Park, Jin Woo

    Oxaliplatin (OXA) is a third-generation cisplatin analog that has been approved as first-line chemotherapy in combination with 5-fluorouracil (5-FU) for the treatment of resectable and advanced colorectal cancer. However, the therapeutic efficacy of oral OXA and 5-FU is limited by their low bioavailability due to poor membrane permeability. The aim of the present study was to develop an oral delivery system for OXA and 5-FU. We constructed an ion-pairing complex of OXA with a deoxycholic acid derivative (N α -deoxycholyl-l-lysyl-methylester, DCK) (OXA/DCK) as a permeation enhancer. Next, we prepared multiple water-in-oil-in-water nanoemulsions incorporating OXA/DCK and 5-FU to enhance their oral absorption. To evaluate their membrane permeability, we assessed in vitro permeabilities of OXA/DCK and 5-FU through an artificial intestinal membrane and Caco-2 cell monolayer. Finally, oral bioavailability in rats and tumor growth inhibition in the colorectal adenocarcinoma cell (CT26)-bearing mouse model were investigated after oral administration of nanoemulsion containing OXA/DCK and 5-FU. The droplet size of the optimized nanoemulsion was 20.3±0.22 nm with a zeta potential of -4.65±1.68 mV. In vitro permeabilities of OXA/DCK and 5-FU from the nanoemulsion through a Caco-2 cell monolayer were 4.80- and 4.30-fold greater than those of OXA and 5-FU, respectively. The oral absorption of OXA/DCK and 5-FU from the nanoemulsion also increased significantly, and the resulting oral bioavailability values of OXA/DCK and 5-FU in the nanoemulsive system were 9.19- and 1.39-fold higher than those of free OXA and 5-FU, respectively. Furthermore, tumor growth in CT26 tumor-bearing mice given the oral OXA/DCK- and 5-FU-loaded nanoemulsion was maximally inhibited by 73.9%, 48.5%, and 38.1%, compared with tumor volumes in the control group and the oral OXA and 5-FU groups, respectively. These findings demonstrate the therapeutic potential of a nanoemulsion incorporating OXA/DCK and

  15. Barcoding against a paradox? Combined molecular species delineations reveal multiple cryptic lineages in elusive meiofaunal sea slugs

    Science.gov (United States)

    2012-01-01

    Background Many marine meiofaunal species are reported to have wide distributions, which creates a paradox considering their hypothesized low dispersal abilities. Correlated with this paradox is an especially high taxonomic deficit for meiofauna, partly related to a lower taxonomic effort and partly to a high number of putative cryptic species. Molecular-based species delineation and barcoding approaches have been advocated for meiofaunal biodiversity assessments to speed up description processes and uncover cryptic lineages. However, these approaches show sensitivity to sampling coverage (taxonomic and geographic) and the success rate has never been explored on mesopsammic Mollusca. Results We collected the meiofaunal sea-slug Pontohedyle (Acochlidia, Heterobranchia) from 28 localities worldwide. With a traditional morphological approach, all specimens fall into two morphospecies. However, with a multi-marker genetic approach, we reveal multiple lineages that are reciprocally monophyletic on single and concatenated gene trees in phylogenetic analyses. These lineages are largely concordant with geographical and oceanographic parameters, leading to our primary species hypothesis (PSH). In parallel, we apply four independent methods of molecular based species delineation: General Mixed Yule Coalescent model (GMYC), statistical parsimony, Bayesian Species Delineation (BPP) and Automatic Barcode Gap Discovery (ABGD). The secondary species hypothesis (SSH) is gained by relying only on uncontradicted results of the different approaches (‘minimum consensus approach’), resulting in the discovery of a radiation of (at least) 12 mainly cryptic species, 9 of them new to science, some sympatric and some allopatric with respect to ocean boundaries. However, the meiofaunal paradox still persists in some Pontohedyle species identified here with wide coastal and trans-archipelago distributions. Conclusions Our study confirms extensive, morphologically cryptic diversity among

  16. HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

    Science.gov (United States)

    Rose, Rebecca; Lamers, Susanna L; Nolan, David J; Maidji, Ekaterina; Faria, N R; Pybus, Oliver G; Dollar, James J; Maruniak, Samuel A; McAvoy, Andrew C; Salemi, Marco; Stoddart, Cheryl A; Singer, Elyse J; McGrath, Michael S

    2016-10-15

    While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In

  17. Machine Learning Approach for Classifying Multiple Sclerosis Courses by Combining Clinical Data with Lesion Loads and Magnetic Resonance Metabolic Features.

    Science.gov (United States)

    Ion-Mărgineanu, Adrian; Kocevar, Gabriel; Stamile, Claudio; Sima, Diana M; Durand-Dubief, Françoise; Van Huffel, Sabine; Sappey-Marinier, Dominique

    2017-01-01

    Purpose: The purpose of this study is classifying multiple sclerosis (MS) patients in the four clinical forms as defined by the McDonald criteria using machine learning algorithms trained on clinical data combined with lesion loads and magnetic resonance metabolic features. Materials and Methods: Eighty-seven MS patients [12 Clinically Isolated Syndrome (CIS), 30 Relapse Remitting (RR), 17 Primary Progressive (PP), and 28 Secondary Progressive (SP)] and 18 healthy controls were included in this study. Longitudinal data available for each MS patient included clinical (e.g., age, disease duration, Expanded Disability Status Scale), conventional magnetic resonance imaging and spectroscopic imaging. We extract N-acetyl-aspartate (NAA), Choline (Cho), and Creatine (Cre) concentrations, and we compute three features for each spectroscopic grid by averaging metabolite ratios (NAA/Cho, NAA/Cre, Cho/Cre) over good quality voxels. We built linear mixed-effects models to test for statistically significant differences between MS forms. We test nine binary classification tasks on clinical data, lesion loads, and metabolic features, using a leave-one-patient-out cross-validation method based on 100 random patient-based bootstrap selections. We compute F1-scores and BAR values after tuning Linear Discriminant Analysis (LDA), Support Vector Machines with gaussian kernel (SVM-rbf), and Random Forests. Results: Statistically significant differences were found between the disease starting points of each MS form using four different response variables: Lesion Load, NAA/Cre, NAA/Cho, and Cho/Cre ratios. Training SVM-rbf on clinical and lesion loads yields F1-scores of 71-72% for CIS vs. RR and CIS vs. RR+SP, respectively. For RR vs. PP we obtained good classification results (maximum F1-score of 85%) after training LDA on clinical and metabolic features, while for RR vs. SP we obtained slightly higher classification results (maximum F1-score of 87%) after training LDA and SVM-rbf on

  18. Lenalidomide in Combination with Dexamethasone in Elderly Patients with Advanced, Relapsed or Refractory Multiple Myeloma and Renal Failure

    Science.gov (United States)

    Tosi, Patrizia; Gamberi, Barbara; Castagnari, Barbara; Molinari, Anna Lia; Savini, Paolo; Ceccolini, Michela; Tani, Monica; Merli, Anna; Imola, Manuela; Mianulli, Anna Maria; Cellini, Claudia; Tomassetti, Simona; Merli, Francesco; Fattori, Pierpaolo; Zaccaria, Alfonso

    2013-01-01

    Salvage therapy of elderly patients with advanced, relapsed and refractory multiple myeloma (MM) is often limited by poor marrow reserve and multi-organ impairment. In particular, renal failure occurs in up to 50% of such patients, and this can potentially limit the therapeutic options. Both thalidomide and bortezomib have proven effective in these patients, with an acceptable toxicity, while, in clinical practice, lenalidomide is generally not considered a first-choice drug for MM patients with renal failure as early reports showed an increased hematological toxicity unless appropriate dose reduction is applied. Aim of this study was a retrospective evaluation of the efficacy of the combination Lenalidomide + Dexamethasone in a population of elderly MM patients treated in 5 Italian Centers. The study included 20 consecutive MM patients (9 M, 11 F, median age 76.5 years) with relapsed (N= 6) or refractory (N=13) MM and moderate to severe renal failure, defined as creatinine clearance (Cr Cl) 50ml/min. Four patients were undergoing hemodyalisis at study entry. 85 % of the patients had been previously treated with bortezomib-containing regimens. Lenalidomide dose was adjusted according to renal function and patients clinical conditions Median treatment duration was 16 months (1–22), therapy was interrupted after 1 21-day cycle in 2 patients. Grade III–IV neutropenia was observed in 7 patients (35%); grade III–IV non hematological toxicity was recorded in 3 cases (28%). A > partial response was observed in 8 patients (40%), 1 of whom obtained a VGPR; 4 additional patients achieved a minor response. Median response duration was 16 months (range 2–19+ months). A complete and partial renal response was obtained in 4 and 3 patients, respectively, all of them were responsive to Lenalidomide-dexamethasone According to our data, LEN+DEX has shown efficacy and acceptable toxicity in this population of elderly patients with advanced MM and renal failure PMID:23795275

  19. Robust Grape Cluster Detection in a Vineyard by Combining the AdaBoost Framework and Multiple Color Components.

    Science.gov (United States)

    Luo, Lufeng; Tang, Yunchao; Zou, Xiangjun; Wang, Chenglin; Zhang, Po; Feng, Wenxian

    2016-12-10

    The automatic fruit detection and precision picking in unstructured environments was always a difficult and frontline problem in the harvesting robots field. To realize the accurate identification of grape clusters in a vineyard, an approach for the automatic detection of ripe grape by combining the AdaBoost framework and multiple color components was developed by using a simple vision sensor. This approach mainly included three steps: (1) the dataset of classifier training samples was obtained by capturing the images from grape planting scenes using a color digital camera, extracting the effective color components for grape clusters, and then constructing the corresponding linear classification models using the threshold method; (2) based on these linear models and the dataset, a strong classifier was constructed by using the AdaBoost framework; and (3) all the pixels of the captured images were classified by the strong classifier, the noise was eliminated by the region threshold method and morphological filtering, and the grape clusters were finally marked using the enclosing rectangle method. Nine hundred testing samples were used to verify the constructed strong classifier, and the classification accuracy reached up to 96.56%, higher than other linear classification models. Moreover, 200 images captured under three different illuminations in the vineyard were selected as the testing images on which the proposed approach was applied, and the average detection rate was as high as 93.74%. The experimental results show that the approach can partly restrain the influence of the complex background such as the weather condition, leaves and changing illumination.

  20. Robust Grape Cluster Detection in a Vineyard by Combining the AdaBoost Framework and Multiple Color Components

    Directory of Open Access Journals (Sweden)

    Lufeng Luo

    2016-12-01

    Full Text Available The automatic fruit detection and precision picking in unstructured environments was always a difficult and frontline problem in the harvesting robots field. To realize the accurate identification of grape clusters in a vineyard, an approach for the automatic detection of ripe grape by combining the AdaBoost framework and multiple color components was developed by using a simple vision sensor. This approach mainly included three steps: (1 the dataset of classifier training samples was obtained by capturing the images from grape planting scenes using a color digital camera, extracting the effective color components for grape clusters, and then constructing the corresponding linear classification models using the threshold method; (2 based on these linear models and the dataset, a strong classifier was constructed by using the AdaBoost framework; and (3 all the pixels of the captured images were classified by the strong classifier, the noise was eliminated by the region threshold method and morphological filtering, and the grape clusters were finally marked using the enclosing rectangle method. Nine hundred testing samples were used to verify the constructed strong classifier, and the classification accuracy reached up to 96.56%, higher than other linear classification models. Moreover, 200 images captured under three different illuminations in the vineyard were selected as the testing images on which the proposed approach was applied, and the average detection rate was as high as 93.74%. The experimental results show that the approach can partly restrain the influence of the complex background such as the weather condition, leaves and changing illumination.

  1. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy

    NARCIS (Netherlands)

    P. Sonneveld (Pieter); R. Hajek (Roman); A. Nagler (Arnon); A. Spencer (Andrew); J. Bladé (Joan); T. Robak (Tadeusz); S.H. Zhuang (Sen); J-L. Harousseau (Jean-Luc); R.Z. Orlowski (Robert)

    2008-01-01

    textabstractBACKGROUND. Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In

  2. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy.

    NARCIS (Netherlands)

    Sonneveld, P.; Hajek, R.; Nagler, A.; Spencer, A.; Blade, J.; Robak, T.; Zhuang, S.H.; Harousseau, J.L.; Orlowski, R.Z.

    2008-01-01

    BACKGROUND: Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In the current

  3. Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients

    NARCIS (Netherlands)

    Waal, de Esther G. M.; de Munck, Linda; Hoogendoorn, Mels; Woolthuis, Gerhard; van der Velden, Annette; Tromp, Yvonne; Vellenga, Edo; Hovenga, Sjoerd

    2015-01-01

    Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of

  4. A Hybrid Chalcone Combining the Trimethoxyphenyl and Isatinyl Groups Targets Multiple Oncogenic Proteins and Pathways in Hepatocellular Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Lili Cao

    Full Text Available Small molecule inhibitors that can simultaneously inhibit multiple oncogenic proteins in essential pathways are promising therapeutic chemicals for hepatocellular carcinoma (HCC. To combine the anticancer effects of combretastatins, chalcones and isatins, we synthesized a novel hybrid molecule 3',4',5'-trimethoxy-5-chloro-isatinylchalcone (3MCIC. 3MCIC inhibited proliferation of cultured HepG2 cells, causing rounding-up of the cells and massive vacuole accumulation in the cytoplasm. Paxillin and focal adhesion plaques were downregulated by 3MCIC. Surprisingly, unlike the microtubule (MT-targeting agent CA-4 that inhibits tubulin polymerization, 3MCIC stabilized tubulin polymers both in living cells and in cell lysates. 3MCIC treatment reduced cyclin B1, CDK1, p-CDK1/2, and Rb, but increased p53 and p21. Moreover, 3MCIC caused GSK3β degradation by promoting GSK3β-Ser9 phosphorylation. Nevertheless, 3MCIC inhibited the Wnt/β-catenin pathway by downregulating β-catenin, c-Myc, cyclin D1 and E2F1. 3MCIC treatment not only activated the caspase-3-dependent apoptotic pathway, but also caused massive autophagy evidenced by rapid and drastic changes of LC3 and p62. 3MCIC also promoted cleavage and maturation of the lysosomal protease cathepsin D. Using ligand-affinity chromatography (LAC, target proteins captured onto the Sephacryl S1000-C12-3MCIC resins were isolated and analyzed by mass spectrometry (MS. Some of the LAC-MS identified targets, i.e., septin-2, vimentin, pan-cytokeratin, nucleolin, EF1α1/2, EBP1 (PA2G4, cyclin B1 and GSK3β, were further detected by Western blotting. Moreover, both septin-2 and HIF-1α decreased drastically in 3MCIC-treated HepG2 cells. Our data suggest that 3MCIC is a promising anticancer lead compound with novel targeting mechanisms, and also demonstrate the efficiency of LAC-MS based target identification in anticancer drug development.

  5. Combined effects of multiple large-scale hydraulic engineering on water stages in the middle Yangtze River

    Science.gov (United States)

    Han, Jianqiao; Sun, Zhaohua; Li, Yitian; Yang, Yunping

    2017-12-01

    Investigation of water stages influenced by human projects provides better understanding of riverine geomorphological processes and river management. Based on hydrological data collected over 60 years, an extreme stage-extreme discharge analysis and a specific-gauge analysis were performed to research the individual and combined effects of multiple engineering projects on a long-term time series of water stages in the middle Yangtze River. Conclusions are as follows. (1) In accordance with the operation years of the Jingjiang cutoff (CF), the Gezhouba Dam (GD), and the Three Gorges Dam (TGD), the time series (1955-2012) was divided into periods of P1 (1955-1970), P2 (1971-1980), P3 (1981-2002), and P4 (2003 - 2012). Water stage changes during P1-P2, P2-P3, and P3-P4 are varied because of the differences in the types and scales of these projects. The stage decreased at Shashi and increased at Luoshan owing to the operation of the CF. Additionally, after the GD was constructed, the low-flow stage decreased in the upstream reach of Chenglingji and increased in its downstream reach, whereas the flood stage merely decreased at Yichang. Moreover, the TGD resulted in an overall decrease in low-flow stages and a limited increase in flood stages because of the differential adjustments of river geometry and resistance between the low-flow channel and flood channel. (2) Although differences existed in the scouring mechanisms between streamwise erosion associated with dams and headward erosion associated with cutoffs, particular bed textures in the gravel reach led to a similar adjustment that stage reduction at Shashi was the greatest of all stations, which caused the flow slope and sediment transport capacity to decrease in the sandy reach. (3) These engineering projects caused changes in average low-flow and flood stages that varied between Yichang (- 1.58 and - 0.08 m respectively), Shashi (- 3.54 and - 0.12 m), and Luoshan (1.15 and 0.97 m) from P1 to P4. However, less

  6. Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based combination therapy from private drug shops in Mukono District, Uganda.

    Science.gov (United States)

    Hansen, Kristian Schultz; Pedrazzoli, Debora; Mbonye, Anthony; Clarke, Sian; Cundill, Bonnie; Magnussen, Pascal; Yeung, Shunmay

    2013-03-01

    In Uganda, as in many parts of Africa, the majority of the population seek treatment for malaria in drug shops as their first point of care; however, parasitological diagnosis is not usually offered in these outlets. Rapid diagnostic tests (RDTs) for malaria have attracted interest in recent years as a tool to improve malaria diagnosis, since they have proved accurate and easy to perform with minimal training. Although RDTs could feasibly be performed by drug shop vendors, it is not known how much customers would be willing to pay for an RDT if offered in these settings. We conducted a contingent valuation survey among drug shop customers in Mukono District, Uganda. Exit interviews were undertaken with customers aged 15 years and above after leaving a drug shop having purchased an antimalarial and/or paracetamol. The bidding game technique was used to elicit the willingness-to-pay (WTP) for an RDT and a course of artemisinin-based combination therapy (ACT) with and without RDT confirmation. Factors associated with WTP were investigated using linear regression. The geometric mean WTP for an RDT was US$0.53, US$1.82 for a course of ACT and US$2.05 for a course of ACT after a positive RDT. Factors strongly associated with a higher WTP for these commodities included having a higher socio-economic status, no fever/malaria in the household in the past 2 weeks and if a malaria diagnosis had been obtained from a qualified health worker prior to visiting the drug shop. The findings further suggest that the WTP for an RDT and a course of ACT among drug shop customers is considerably lower than prevailing and estimated end-user prices for these commodities. Increasing the uptake of ACTs in drug shops and restricting the sale of ACTs to parasitologically confirmed malaria will therefore require additional measures.

  7. Diagnostic Utility of Alpha-fetoprotein and Des-gamma ...

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... reports on the clinical characteristics of hepatocellular carcinoma in relation to the combination of the two tumor markers in .... Data were expressed as means ± standard deviations. Multiple comparisons were .... that C-reactive protein has significant diagnostic power in AFP-negative, HBV-related HCC.[23].

  8. Improved diagnostic accuracy of Alzheimer's disease by combining regional cortical thickness and default mode network functional connectivity: Validated in the Alzheimer's disease neuroimaging initiative set

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Eun; Park, Bum Woo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Jung; Oh, Joo Young; Shim, Woo Hyun [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Jae Hong; Roh, Jee Hoon [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2017-11-15

    To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease.

  9. Combination of real-time PCR and sequencing to detect multiple clinically relevant genetic variations in the lactase gene.

    Science.gov (United States)

    Brasen, Claus Lohman; Frischknecht, Lone; Ørnskov, Dorthe; Andreasen, Lotte; Madsen, Jonna Skov

    2017-02-01

    Lactase persistence is an autosomal dominant trait commonly distributed in Europe as well as some parts of east Africa and the Arabian Peninsula. Using real-time PCR to detect the -13910C > T variant common in the European population is a reliable analysis although other variants in the probe-binding site may cause errors in analysis. The aim of this study was to determine the prevalence of the variants in a Danish cohort examined for lactose intolerance as well as to improve the real-time PCR analysis for detection of the different variants. We genotyped 3395 routine samples using real-time PCR for the -13910C > T-variant. All consecutive samples identified as -13910CC were sequenced using Sanger Sequencing. Using the SDS software we examined various quality value settings to improve on the genetic analysis. Using real-time PCR resulted in 100% successful genotyping of the -13910C > T variant. By using a quality value of 99% and sequencing the undetermined samples we improved the ability of the assay to identify variants other than -13910C > T. This resulted in a reduction of the diagnostic error rate by a factor of 2.4 while increasing the expenses only 3%. We conclude that using a quality value of 99% in the SDS software significantly improves the diagnostic efficiency of the real-time PCR assay for detecting variants associated to lactase persistence.

  10. HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase

    NARCIS (Netherlands)

    Ferdinandusse, Sacha; Waterham, Hans R.; Heales, Simon J. R.; Brown, Garry K.; Hargreaves, Iain P.; Taanman, Jan-Willem; Gunny, Roxana; Abulhoul, Lara; Wanders, Ronald J. A.; Clayton, Peter T.; Leonard, James V.; Rahman, Shamima

    2013-01-01

    Deficiency of 3-hydroxy-isobutyryl-CoA hydrolase (HIBCH) caused by HIBCH mutations is a rare cerebral organic aciduria caused by disturbance of valine catabolism. Multiple mitochondrial respiratory chain (RC) enzyme deficiencies can arise from a number of mechanisms, including defective maintenance

  11. Emergence of Multiple Human Cytomegalovirus Ganciclovir-Resistant Mutants with Deletions and Substitutions within the UL97 Gene in a Patient with Severe Combined Immunodeficiency

    Science.gov (United States)

    Wolf, Dana G.; Yaniv, Isaac; Ashkenazi, Shai; Honigman, Alik

    2001-01-01

    Infection with multiple ganciclovir-resistant human cytomegalovirus mutants, containing different substitutions and deletions in the UL97 gene, was found in a patient with severe combined immunodeficiency (SCID) within 3 weeks of ganciclovir therapy. A novel 11-codon deletion at positions 590 to 600 was identified. These unique findings may be related to the nature of the immunodeficiency in the SCID patient. PMID:11158760

  12. Triple Combination of Oseltamivir, Amantadine, and Ribavirin Displays Synergistic Activity against Multiple Influenza Virus Strains In Vitro ▿

    Science.gov (United States)

    Nguyen, Jack T.; Hoopes, Justin D.; Smee, Donald F.; Prichard, Mark N.; Driebe, Elizabeth M.; Engelthaler, David M.; Le, Minh H.; Keim, Paul S.; Spence, R. Paul; Went, Gregory T.

    2009-01-01

    The recurring emergence of influenza virus strains that are resistant to available antiviral medications has become a global health concern, especially in light of the potential for a new influenza virus pandemic. Currently, virtually all circulating strains of influenza A virus in the United States are resistant to either of the two major classes of anti-influenza drugs (adamantanes and neuraminidase inhibitors). Thus, new therapeutic approaches that can be rapidly deployed and that will address the issue of recurring resistance should be developed. We have tested double and triple combinations of the approved anti-influenza drugs oseltamivir and amantadine together with ribavirin against three influenza virus strains using cytopathic effect inhibition assays in MDCK cells. We selected A/New Caledonia/20/99 (H1N1) and A/Sydney/05/97 (H3N2) as representatives of the wild-type versions of the predominant circulating seasonal influenza virus strains and A/Duck/MN/1525/81 (H5N1) as a representative of avian influenza virus strains. Dose-response curves were generated for all drug combinations, and the degree of drug interaction was quantified using a model that calculates the synergy (or antagonism) between the drugs in double and triple combinations. This report demonstrates that a triple combination of antivirals was highly synergistic against influenza A virus. Importantly, the synergy of the triple combination was 2- to 13-fold greater than the synergy of any double combination depending on the influenza virus subtype. These data support the investigation of a novel combination of oseltamivir, amantadine, and ribavirin as an effective treatment for both seasonal and pandemic influenza virus, allowing the efficient use of the existing drug supplies. PMID:19620324

  13. Revisiting Tversky's diagnosticity principle

    OpenAIRE

    Evers, Ellen R. K.; Daniel eLakens

    2014-01-01

    Similarity is a fundamental concept in cognition. In 1977 Amos Tversky published a highly influential feature-based model of how people judge the similarity between objects. The model highlights the context-dependence of similarity judgments, and challenged geometric models of similarity. One of the context-dependent effects Tversky describes is the diagnosticity principle. The diagnosticity principle determines which features are used to cluster multiple objects into subgroups. Perceived sim...

  14. Development and Application of a Two-Tier Multiple-Choice Diagnostic Test for High School Students' Understanding of Cell Division and Reproduction

    Science.gov (United States)

    Sesli, Ertugrul; Kara, Yilmaz

    2012-01-01

    This study involved the development and application of a two-tier diagnostic test for measuring students' understanding of cell division and reproduction. The instrument development procedure had three general steps: defining the content boundaries of the test, collecting information on students' misconceptions, and instrument development.…

  15. Combination of real-time PCR and sequencing to detect multiple clinically relevant genetic variations in the lactase gene

    DEFF Research Database (Denmark)

    Brasen, Claus Lohman; Frischknecht, Lone; Ørnskov, Dorthe

    2017-01-01

    in the probe-binding site may cause errors in analysis. The aim of this study was to determine the prevalence of the variants in a Danish cohort examined for lactose intolerance as well as to improve the real-time PCR analysis for detection of the different variants. METHODS: We genotyped 3395 routine samples...... genotyping of the -13910C > T variant. By using a quality value of 99% and sequencing the undetermined samples we improved the ability of the assay to identify variants other than -13910C > T. This resulted in a reduction of the diagnostic error rate by a factor of 2.4 while increasing the expenses only 3...

  16. Diagnostic Support for Selected Paediatric Pulmonary Diseases Using Answer-Pattern Recognition in Questionnaires Based on Combined Data Mining Applications--A Monocentric Observational Pilot Study.

    Directory of Open Access Journals (Sweden)

    Ann-Katrin Rother

    Full Text Available Clinical symptoms in children with pulmonary diseases are frequently non-specific. Rare diseases such as primary ciliary dyskinesia (PCD, cystic fibrosis (CF or protracted bacterial bronchitis (PBB can be easily missed at the general practitioner (GP.To develop and test a questionnaire-based and data mining-supported tool providing diagnostic support for selected pulmonary diseases.First, interviews with parents of affected children were conducted and analysed. These parental observations during the pre-diagnostic time formed the basis for a new questionnaire addressing the parents' view on the disease. Secondly, parents with a sick child (e.g. PCD, PBB answered the questionnaire and a data base was set up. Finally, a computer program consisting of eight different classifiers (support vector machine (SVM, artificial neural network (ANN, fuzzy rule-based, random forest, logistic regression, linear discriminant analysis, naive Bayes and nearest neighbour and an ensemble classifier was developed and trained to categorise any given new questionnaire and suggest a diagnosis. For estimating the diagnostic accuracy, we applied ten-fold stratified cross validation.All questionnaires of patients suffering from CF, asthma (AS, PCD, acute bronchitis (AB and the healthy control group were correctly diagnosed by the fusion algorithm. For the pneumonia (PM group 19/21 (90.5% and for the PBB group 17/18 (94.4% correct diagnoses could be reached. The program detected the correct diagnoses with an overall sensitivity of 98.8%. Receiver operating characteristics (ROC analyses confirmed the accuracy of this diagnostic tool. Case studies highlighted the applicability of the tool in the daily work of a GP.For children with symptoms of pulmonary diseases a questionnaire-based diagnostic support tool using data mining techniques exhibited good results in arriving at diagnostic suggestions. In the hands of a doctor, this tool could be of value in arousing awareness for

  17. Slip regulation for anti-lock braking systems using multiple surface sliding controller combined with inertial delay control

    Science.gov (United States)

    Verma, Rahul; Ginoya, Divyesh; Shendge, P. D.; Phadke, S. B.

    2015-08-01

    In this paper, a multiple surface sliding controller is designed for an anti-lock braking system to maintain the slip ratio at a desired level. Various types of uncertainties coming from unknown road surface conditions, the variations in normal force and the mass of the vehicle are estimated using an uncertainty estimation technique called the inertial delay control and then the estimate is used in the design of the multiple surface sliding controller. The proposed scheme does not require the bounds of uncertainties. The ultimate boundedness of the overall system is proved. The proposed scheme is validated by simulation under various scenarios of road friction, road gradient and vehicle loading followed by experimentation on a laboratory anti-lock braking set-up for different friction conditions.

  18. A combined QC methodology in Ebro Delta HF radar system: real time web monitoring of diagnostic parameters and offline validation of current data

    Science.gov (United States)

    Lorente, Pablo; Piedracoba, Silvia; Soto-Navarro, Javier; Ruiz, Maria Isabel; Alvarez Fanjul, Enrique

    2015-04-01

    Over recent years, special attention has been focused on the development of protocols for near real-time quality control (QC) of HF radar derived current measurements. However, no agreement has been worldwide achieved to date to establish a standardized QC methodology, although a number of valuable international initiatives have been launched. In this context, Puertos del Estado (PdE) aims to implement a fully operational HF radar network with four different Codar SeaSonde HF radar systems by means of: - The development of a best-practices robust protocol for data processing and QC procedures to routinely monitor sites performance under a wide variety of ocean conditions. - The execution of validation works with in-situ observations to assess the accuracy of HF radar-derived current measurements. The main goal of the present work is to show this combined methodology for the specific case of Ebro HF radar (although easily expandable to the rest of PdE radar systems), deployed to manage Ebro River deltaic area and promote the conservation of an important aquatic ecosystem exposed to a severe erosion and reshape. To this aim, a web interface has been developed to efficiently monitor in real time the evolution of several diagnostic parameters provided by the manufacturer (CODAR) and used as indicators of HF radar system health. This web, updated automatically every hour, examines sites performance on different time basis in terms of: - Hardware parameters: power and temperature. - Radial parameters, among others: Signal-to-Noise Ratio (SNR), number of radial vectors provided by time step, maximum radial range and bearing. - Total uncertainty metrics provided by CODAR: zonal and meridional standard deviations and covariance between both components. - Additionally, a widget embedded in the web interface executes queries against PdE database, providing the chance to compare current time series observed by Tarragona buoy (located within Ebro HF radar spatial domain) and

  19. Multiple Olefin Metathesis Polymerization That Combines All Three Olefin Metathesis Transformations: Ring-Opening, Ring-Closing, and Cross Metathesis.

    Science.gov (United States)

    Lee, Ho-Keun; Bang, Ki-Taek; Hess, Andreas; Grubbs, Robert H; Choi, Tae-Lim

    2015-07-29

    We demonstrated tandem ring-opening/ring-closing metathesis (RO/RCM) polymerization of monomers containing two cyclopentene moieties and postmodification via insertion polymerization. In this system, well-defined polymers were efficiently formed by tandem cascade RO/RCM reaction pathway. Furthermore, these polymers could be transformed to new A,B-alternating copolymers via a sequential cross metathesis reaction with a diacrylate. Additionally, we demonstrated the concept of multiple olefin metathesis polymerization in which the dicyclopentene and diacrylate monomers underwent all three olefin metathesis transformations (ring-opening, ring-closing, and cross metathesis) in one shot to produce A,B-alternating copolymer.

  20. Combining Genes from Multiple Phages for Improved Cell Lysis and DNA Transfer from Escherichia coli to Bacillus subtilis.

    Directory of Open Access Journals (Sweden)

    Mario Juhas

    Full Text Available The ability to efficiently and reliably transfer genetic circuits between the key synthetic biology chassis, such as Escherichia coli and Bacillus subtilis, constitutes one of the major hurdles of the rational genome engineering. Using lambda Red recombineering we integrated the thermosensitive lambda repressor and the lysis genes of several bacteriophages into the E. coli chromosome. The lysis of the engineered autolytic cells is inducible by a simple temperature shift. We improved the lysis efficiency by introducing different combinations of lysis genes from bacteriophages lambda, ΦX174 and MS2 under the control of the thermosensitive lambda repressor into the E. coli chromosome. We tested the engineered autolytic cells by transferring plasmid and bacterial artificial chromosome (BAC-borne genetic circuits from E. coli to B. subtilis. Our engineered system combines benefits of the two main synthetic biology chassis, E. coli and B. subtilis, and allows reliable and efficient transfer of DNA edited in E. coli into B. subtilis.

  1. Gene-based multiple regression association testing for combined examination of common and low frequency variants in quantitative trait analysis.

    Science.gov (United States)

    Yoo, Yun Joo; Sun, Lei; Bull, Shelley B

    2013-01-01

    Multi-marker methods for genetic association analysis can be performed for common and low frequency SNPs to improve power. Regression models are an intuitive way to formulate multi-marker tests. In previous studies we evaluated regression-based multi-marker tests for common SNPs, and through identification of bins consisting of correlated SNPs, developed a multi-bin linear combination (MLC) test that is a compromise between a 1 df linear combination test and a multi-df global test. Bins of SNPs in high linkage disequilibrium (LD) are identified, and a linear combination of individual SNP statistics is constructed within each bin. Then association with the phenotype is represented by an overall statistic with df as many or few as the number of bins. In this report we evaluate multi-marker tests for SNPs that occur at low frequencies. There are many linear and quadratic multi-marker tests that are suitable for common or low frequency variant analysis. We compared the performance of the MLC tests with various linear and quadratic statistics in joint or marginal regressions. For these comparisons, we performed a simulation study of genotypes and quantitative traits for 85 genes with many low frequency SNPs based on HapMap Phase III. We compared the tests using (1) set of all SNPs in a gene, (2) set of common SNPs in a gene (MAF ≥ 5%), (3) set of low frequency SNPs (1% ≤ MAF analysis using all SNPs including common and low frequency SNPs is a good and robust choice whereas using common SNPs alone or low frequency SNP alone can lose power. MLC tests performed well in combined analysis except where two low frequency causal SNPs with opposing effects are positively correlated. Overall, across different sets of analysis, the joint regression Wald test showed consistently good performance whereas other statistics including the ones based on marginal regression had lower power for some situations.

  2. High-intensity interval training combined with resistance training improves physiological capacities, strength and quality of life in multiple sclerosis patients: a pilot study.

    Science.gov (United States)

    Zaenker, Pierre; Favret, Fabrice; Lonsdorfer, Evelyne; Muff, Guillaume; DE Seze, Jérôme; Isner-Horobeti, Marie-Eve

    2017-07-05

    Numerous studies have shown that mild-to-moderate intensity or resistance exercise training improves physical capacities such as, peak oxygen consumption, maximal tolerated power and strength in multiple sclerosis patients. However, few studies have evaluated the effects of high intensity interval training associated to with resistance training. Only few studies have analysed difference between men and women before and after combined training. Moreover, the evaluation of exercise between ambulatory multiple sclerosis patients without disability (EDSS 0- 3) and patients with disabilities (EDSS 3.5-5) was not largely published. The main objective of our study was to determine if high intensity interval training combined with resistance training improved aerobic and strength capacities as well as quality of life in multiple sclerosis patients and if gender and disabilities play a role in these changes. This study was an open-label uncontrolled study. The study was performed outside from conventional care facilities and including homebased training. 26 multiple sclerosis patients have completed the program (19 women/7men, Age 44.6+7.9years, Expanded Disability Status Score 2 (0-5)). We conducted a 12-week programme of high intensity interval training combined with resistance training at body weight. Peak oxygen consumption, maximal tolerated power, lactates, isokinetic strength of quadriceps and hamstrings (at 90°/sec, 180°/sec and 240°/sec) and quality of life were evaluated before and after the programme. Peak oxygen consumption and maximum tolerated power improved by 13.5% and 9.4%, respectively. Isokinetic muscle strength increased in both quadriceps and hamstrings at each speed, with a rebalancing of strength between the two legs in quadriceps. Quality of life was also enhanced in three domains. Women showed better improvements than men in VO2peak, maximal tolerated power, lactates at the end of test, and heart rate peak, strength in both quadriceps and

  3. Influence of cytokinins in combination with GA₃ on shoot multiplication and elongation of tea clone Iran 100 (Camellia sinensis (L.) O. Kuntze).

    Science.gov (United States)

    Gonbad, Reza Azadi; Rani Sinniah, Uma; Aziz, Maheran Abdul; Mohamad, Rosfarizan

    2014-01-01

    The use of in vitro culture has been accepted as an efficient technique for clonal propagation of many woody plants. In the present research, we report the results of a number of experiments aimed at optimizing micropropagation protocol for tea (Camellia sinensis (L.) O. Kuntze) (clone Iran 100) using nodal segments as the explant. The effect of different combinations and concentrations of plant growth regulators (PGR) (BAP, TDZ, GA₃) on shoot multiplication and elongation was assessed. The influence of exposure to IBA in liquid form prior to transfer to solid media on rooting of tea microshoots was investigated. The results of this study showed that the best treatment for nodal segment multiplication in terms of the number of shoot per explant and shoot elongation was obtained using 3 mg/L BAP in combination with 0.5 mg/L GA₃. TDZ was found to be inappropriate for multiplication of tea clone Iran 100 as it resulted in hyperhydricity especially at concentrations higher than 0.05 mg/L. Healthy shoots treated with 300 mg/L IBA for 30 min followed by transfer to 1/2 strength MS medium devoid of PGR resulted in 72.3% of shoots producing roots and upon transferring them to acclimatization chamber 65% survival was obtained prior to field transfer.

  4. Influence of Cytokinins in Combination with GA3 on Shoot Multiplication and Elongation of Tea Clone Iran 100 (Camellia sinensis (L.) O. Kuntze)

    Science.gov (United States)

    Gonbad, Reza Azadi; Mohamad, Rosfarizan

    2014-01-01

    The use of in vitro culture has been accepted as an efficient technique for clonal propagation of many woody plants. In the present research, we report the results of a number of experiments aimed at optimizing micropropagation protocol for tea (Camellia sinensis (L.) O. Kuntze) (clone Iran 100) using nodal segments as the explant. The effect of different combinations and concentrations of plant growth regulators (PGR) (BAP, TDZ, GA3) on shoot multiplication and elongation was assessed. The influence of exposure to IBA in liquid form prior to transfer to solid media on rooting of tea microshoots was investigated. The results of this study showed that the best treatment for nodal segment multiplication in terms of the number of shoot per explant and shoot elongation was obtained using 3 mg/L BAP in combination with 0.5 mg/L GA3. TDZ was found to be inappropriate for multiplication of tea clone Iran 100 as it resulted in hyperhydricity especially at concentrations higher than 0.05 mg/L. Healthy shoots treated with 300 mg/L IBA for 30 min followed by transfer to 1/2 strength MS medium devoid of PGR resulted in 72.3% of shoots producing roots and upon transferring them to acclimatization chamber 65% survival was obtained prior to field transfer. PMID:24605069

  5. [EFFECTIVENESS OF ONE-STAGE REPAIR AND RECONSTRUCTION OF TRAUMATIC DISLOCATION OF KNEE JOINT COMBINED WITH MULTIPLE LIGAMENT INJURIES].

    Science.gov (United States)

    Jiang, Wu; Yao, Jianhua; Kong, Dejia; Sun, Wei; Huang, Yan; Zheng, Huayong; Liu, Chen; Bao, Xianguo

    2014-07-01

    To investigate the effectiveness of one-stage repair and reconstruction of multiple ligament injuries of the knee under arthroscopy. Between March 2007 and March 2009, 25 patients (25 knees) with multiple ligament injuries of the knee underwent one-stage repair and reconstruction under arthroscopy. Of 25 cases, 16 were male and 9 were female with an average age of 29.6 years (range, 18-43 years). The causes of injury were traffic accident injury in 20 cases, falling injury from height in 3 cases, and sport injury in 2 cases. The time between injury and surgery was 8-14 days (mean, 10.5 days). The preoperative Lysholm score was 37.92 ± 3.57. The X-ray film and MRI examinations showed that 17 patients had tears of anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and medial collateral ligament, and 8 patients had tears of ACL, PCL, and posterolateral corner (PLC); 5 cases had medial meniscus injury and 7 cases had lateral meniscus injury. The ACL, PCL, and PLC were reconstructed under arthroscopy with autologous tendon or allogeneic tendon, and the MCL was repaired. Early active and passive functional exercises were done postoperatively. All the incisions healed by first intention, and there was no complications of infection and deep venous thrombosis. Twenty-five patients were followed up 24-78 months (mean, 50.9 months). Six patients had knee stiff postoperatively; after manipulation under anesthsia, 5 patients lost less than 15° of flexion and only 1 patient lost 26° of flexion. At last follow-up, the stability of the knee joint was significantly improved. There were significant differences in the anterior drawer test, posterior drawer test, Lachman test, and varus stress and valgus stress testing at 30° between at last follow-up and at preoperation (P Knee Documentation Committee (IKDC) rating was nearly normal in 16 cases (64%), abnormal in 8 cases (32%), and obviously abnormal in 1 case (4%). One-stage repair and reconstruction of

  6. The combination of energy-dependent internal adaptation mechanisms and external factors enables Listeria monocytogenes to express a strong starvation survival response during multiple-nutrient starvation.

    Science.gov (United States)

    Lungu, Bwalya; Saldivar, Joshua C; Story, Robert; Ricke, Steven C; Johnson, Michael G

    2010-05-01

    The goal of this study was to characterize the starvation survival response (SSR) of a wild-type Listeria monocytogenes 10403S and an isogenic DeltasigB mutant strain during multiple-nutrient starvation conditions over 28 days. This study examined the effects of inhibitors of protein synthesis, the proton motive force, substrate level phosphorylation, and oxidative phosphorylation on the SSR of L. monocytogenes 10403S and a DeltasigB mutant during multiple-nutrient starvation. The effects of starvation buffer changes on viability were also examined. During multiple-nutrient starvation, both strains expressed a strong SSR, suggesting that L. monocytogenes possesses SigB-independent mechanism(s) for survival during multiple-nutrient starvation. Neither strain was able to express an SSR following starvation buffer changes, indicating that the nutrients/factors present in the starvation buffer could be a source of energy for cell maintenance and survival. Neither the wild-type nor the DeltasigB mutant strain was able to elicit an SSR when exposed to the protein synthesis inhibitor chloramphenicol within the first 4 h of starvation. However, both strains expressed an SSR when exposed to chloramphenicol after 6 h or more of starvation, suggesting that the majority of proteins required to elicit an effective SSR in L. monocytogenes are likely produced somewhere between 4 and 6 h of starvation. The varying SSRs of both strains to the different metabolic inhibitors under aerobic or anaerobic conditions suggested that (1) energy derived from the proton motive force is important for an effective SSR, (2) L. monocytogenes utilizes an anaerobic electron transport during multiple-nutrient starvation conditions, and (3) the glycolytic pathway is an important energy source during multiple-nutrient starvation when oxygen is available, and less important under anaerobic conditions. Collectively, the data suggest that the combination of energy-dependent internal adaptation mechanisms

  7. Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations

    Directory of Open Access Journals (Sweden)

    Aurelio Lopez

    2015-01-01

    Full Text Available We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients and more aggressive forms of disease (32 patients were the most common patterns of relapse. After second-line therapy, 75 (51.7% patients achieved at partial response and 16 (11% complete response (CR. Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037, in patients achieving CR (28.3 vs. 14.8 months; P=0.04, and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007.

  8. Combining phylogeography with distribution modeling: multiple Pleistocene range expansions in a parthenogenetic gecko from the Australian arid zone.

    Directory of Open Access Journals (Sweden)

    Jared L Strasburg

    2007-08-01

    Full Text Available Phylogenetic and geographic evidence suggest that many parthenogenetic organisms have evolved recently and have spread rapidly. These patterns play a critical role in our understanding of the relative merits of sexual versus asexual reproductive modes, yet their interpretation is often hampered by a lack of detail. Here we present a detailed phylogeographic study of a vertebrate parthenogen, the Australian gecko Heteronotia binoei, in combination with statistical and biophysical modeling of its distribution during the last glacial maximum. Parthenogenetic H. binoei occur in the Australian arid zone and have the widest range of any known vertebrate parthenogen. They are broadly sympatric with their sexual counterparts, from which they arose via hybridization. We have applied nested clade phylogeographic, effective migration, and mismatch distribution analyses to mitochondrial DNA (mtDNA sequences obtained for 319 individuals sampled throughout the known geographic ranges of two parthenogenetic mitochondrial lineages. These analyses provide strong evidence for past range expansion events from west to east across the arid zone, and for continuing eastward range expansion. Parthenogen formation and range expansion events date to the late Pleistocene, with one lineage expanding from the northwest of its present range around 240,000 years ago and the second lineage expanding from the far west around 70,000 years ago. Statistical and biophysical distribution models support these inferences of recent range expansion, with suitable climatic conditions during the last glacial maximum most likely limited to parts of the arid zone north and west of much of the current ranges of these lineages. Combination of phylogeographic analyses and distribution modeling allowed considerably stronger inferences of the history of this complex than either would in isolation, illustrating the power of combining complementary analytical approaches.

  9. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma.

    Science.gov (United States)

    Santo, Loredana; Hideshima, Teru; Kung, Andrew L; Tseng, Jen-Chieh; Tamang, David; Yang, Min; Jarpe, Matthew; van Duzer, John H; Mazitschek, Ralph; Ogier, Walter C; Cirstea, Diana; Rodig, Scott; Eda, Homare; Scullen, Tyler; Canavese, Miriam; Bradner, James; Anderson, Kenneth C; Jones, Simon S; Raje, Noopur

    2012-03-15

    Histone deacetylase (HDAC) enzymatic activity has been linked to the transcription of DNA in cancers including multiple myeloma (MM). Therefore, HDAC inhibitors used alone and in combination are being actively studied as novel therapies in MM. In the present study, we investigated the preclinical activity of ACY-1215, an HDAC6-selective inhibitor, alone and in combination with bortezomib in MM. Low doses of ACY-1215 combined with bortezomib triggered synergistic anti-MM activity, resulting in protracted endoplasmic reticulum stress and apoptosis via activation of caspase-3, caspase-8, and caspase-9 and poly (ADP) ribosome polymerase. In vivo, the anti-MM activity of ACY-1215 in combination with bortezomib was confirmed using 2 different xenograft SCID mouse models: human MM injected subcutaneously (the plasmacytoma model) and luciferase-expressing human MM injected intravenously (the disseminated MM model). Tumor growth was significantly delayed and overall survival was significantly prolonged in animals treated with the combination therapy. Pharmacokinetic data showed peak plasma levels of ACY-1215 at 4 hours after treatment coincident with an increase in acetylated α-tubulin, a marker of HDAC6 inhibition, by immunohistochemistry and Western blot analysis. These studies provide preclinical rationale for acetylated α-tubulin use as a pharmacodynamic biomarker in future clinical trials.

  10. Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

    NARCIS (Netherlands)

    Garderet, L.; Iacobelli, S.; Moreau, P.; Dib, M.; Lafon, I.; Niederwieser, D.; Masszi, T.; Fontan, J.; Michallet, M.; Gratwohl, A.; Milone, G.; Doyen, C.; Pegourie, B.; Hajek, R.; Casassus, P.; Kolb, B.; Chaleteix, C.; Hertenstein, B.; Onida, F.; Ludwig, H.; Ketterer, N.; Koenecke, C.; Os, M. van; Mohty, M.; Cakana, A.; Gorin, N.C.; Witte, T.J. de; Harousseau, J.L.; Morris, C.; Gahrton, G.

    2012-01-01

    PURPOSE This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous

  11. Effect of Combination Exercise Therapy on Walking Distance, Postural Balance, Fatigue and Quality of Life in Multiple Sclerosis Patients: A Clinical Trial Study

    Science.gov (United States)

    Sangelaji, Bahram; Nabavi, Seyed Massood; Estebsari, Fatemeh; Banshi, Mohammad Reza; Rashidian, Hamideh; Jamshidi, Ensiyeh; Dastoorpour, Maryam

    2014-01-01

    Background: Multiple Sclerosis (MS) is a demyelinating disease of the nervous system which has numerous disabling effects on patients. Objectives: This study aimed at investigating the short- and long-term effects of a period of combination exercise therapy on walking distance, balance, fatigue and quality of life in multiple sclerosis patients referred to the physiotherapy clinic of Iran's Multiple Sclerosis Society in 2013. Patients and Methods: This study was a randomized controlled clinical trial on 59 patients divided into the intervention (n = 39) and control groups (n = 20). The intervention group received 10 weeks of combination therapy including aerobic, strengthening, balancing and stretching exercises. A week before, a week later and a year after the beginning of the exercises, both groups of patients received BBSS, six minute walking, Family Support Services (FSS), Expanded Disability Status Scale (EDSS) and quality of life tests. The scores of two groups were then compared using statistical tests such as repeated measures ANOVA test. Results: The results indicated significant changes in the intervention group in comparison to the control group in the second phase of the study comparing to the first one for all tests except EDSS (Mean difference scores of EDSS: -0.13), P-value = 0.60; FSS: -6.9, P-value = 0.02, Mental Quality of Life (QOL): 16.36, P-value = 0.001; Physical QOL: 12.17, P-value = 0.001, six minute walking: 137.2, P-value multiple sclerosis, and cessation of exercise may cause recurrence of symptoms in the intervention group with a slope similar to that of the control group. Therefore, continuous rather than short period exercises have valuable symptomatic and supportive relief effects in patients. PMID:25068045

  12. Ruxolitinib and Polycation Combination Treatment Overcomes Multiple Mechanisms of Resistance of Pancreatic Cancer Cells to Oncolytic Vesicular Stomatitis Virus.

    Science.gov (United States)

    Felt, Sébastien A; Droby, Gaith N; Grdzelishvili, Valery Z

    2017-08-15

    Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV). Although VSV is effective against a majority of pancreatic ductal adenocarcinoma cell (PDAC) cell lines, some PDAC cell lines are highly resistant to VSV, and the mechanisms of resistance are still unclear. JAK1/2 inhibitors (such as ruxolitinib and JAK inhibitor I) strongly stimulate VSV replication and oncolysis in all resistant cell lines but only partially improve the susceptibility of resistant PDACs to VSV. VSV tumor tropism is generally dependent on the permissiveness of malignant cells to viral replication rather than on receptor specificity, with several ubiquitously expressed cell surface molecules playing a role in VSV attachment to host cells. However, as VSV attachment to PDAC cells has never been tested before, here we examined if it was possibly inhibited in resistant PDAC cells. Our data show a dramatically weaker attachment of VSV to HPAF-II cells, the most resistant human PDAC cell line. Although sequence analysis of low-density lipoprotein (LDL) receptor (LDLR) mRNA did not reveal any amino acid substitutions in this cell line, HPAF-II cells displayed the lowest level of LDLR expression and dramatically lower LDL uptake. Treatment of cells with various statins strongly increased LDLR expression levels but did not improve VSV attachment or LDL uptake in HPAF-II cells. However, LDLR-independent attachment of VSV to HPAF-II cells was dramatically improved by treating cells with Polybrene or DEAE-dextran. Moreover, combining VSV with ruxolitinib and Polybrene or DEAE-dextran successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication.IMPORTANCE Oncolytic virus (OV) therapy is an anticancer approach that uses viruses that selectively infect and kill cancer cells. This study focuses on oncolytic vesicular stomatitis virus (VSV) against pancreatic ductal adenocarcinoma (PDAC) cells. Although VSV is effective against most PDAC

  13. Risk Assessment and Prediction of Flyrock Distance by Combined Multiple Regression Analysis and Monte Carlo Simulation of Quarry Blasting

    Science.gov (United States)

    Armaghani, Danial Jahed; Mahdiyar, Amir; Hasanipanah, Mahdi; Faradonbeh, Roohollah Shirani; Khandelwal, Manoj; Amnieh, Hassan Bakhshandeh

    2016-09-01

    Flyrock is considered as one of the main causes of human injury, fatalities, and structural damage among all undesirable environmental impacts of blasting. Therefore, it seems that the proper prediction/simulation of flyrock is essential, especially in order to determine blast safety area. If proper control measures are taken, then the flyrock distance can be controlled, and, in return, the risk of damage can be reduced or eliminated. The first objective of this study was to develop a predictive model for flyrock estimation based on multiple regression (MR) analyses, and after that, using the developed MR model, flyrock phenomenon was simulated by the Monte Carlo (MC) approach. In order to achieve objectives of this study, 62 blasting operations were investigated in Ulu Tiram quarry, Malaysia, and some controllable and uncontrollable factors were carefully recorded/calculated. The obtained results of MC modeling indicated that this approach is capable of simulating flyrock ranges with a good level of accuracy. The mean of simulated flyrock by MC was obtained as 236.3 m, while this value was achieved as 238.6 m for the measured one. Furthermore, a sensitivity analysis was also conducted to investigate the effects of model inputs on the output of the system. The analysis demonstrated that powder factor is the most influential parameter on fly rock among all model inputs. It is noticeable that the proposed MR and MC models should be utilized only in the studied area and the direct use of them in the other conditions is not recommended.

  14. Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Shenghao Wu

    2015-01-01

    Full Text Available Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM patients with the therapy of subcutaneous (subQ administration of bortezomib and dexamethasone plus thalidomide (VTD regimen. Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group.The efficacy and safety of two groups were analyzed retrospectively. Results. The overall remission (OR after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05. No significant differences in time to 1-year estimate of overall survival (72% versus 75%, P=0.848 and progression-free survival (median 22 months versus 25 months; P=0.725 between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50% than VTD group (80%, P=0.015. Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

  15. Effect of 8-Week Aquatic, Land- based and Combined (Aquatic-Land Training Programs On Walking Capacity in Women with Multiple Sclerosis (MS: A Burdenko Approach

    Directory of Open Access Journals (Sweden)

    Raheleh Ghaffari

    2017-10-01

    Full Text Available Multiple sclerosis (MS is a chronic disease affecting all aspects of life in patients with this disease and causes a wide range of functional problems, including reduced walking capacity. The aim of this study was to compare the effects of 8 weeks aquatic, land-based and combined (aquatic-land (exercise programs according to Burdenko method on the walking capacity measured by 6-Minute Walk Test (6MWT. This was a pre- post design study. Thirty one women diagnosed with MS, age range 30-50 years, EDSS0.05. According to the results of this study, the combined and land-based exercises can be suggested for people with MS in order to improve their walking capacity. These methods can be suggested as appropriate non-pharmacologic complementary therapies in the rehabilitation centers.

  16. Combination-targeting to multiple endothelial cell adhesion molecules modulates binding, endocytosis, and in vivo biodistribution of drug nanocarriers and their therapeutic cargoes.

    Science.gov (United States)

    Papademetriou, Iason; Tsinas, Zois; Hsu, Janet; Muro, Silvia

    2014-08-28

    Designing of drug nanocarriers to aid delivery of therapeutics is an expanding field that can improve medical treatments. Nanocarriers are often functionalized with elements that recognize cell-surface molecules involved in subcellular transport to improve targeting and endocytosis of therapeutics. Combination-targeting using several affinity elements further modulates this outcome. The most studied example is endothelial targeting via multiple cell adhesion molecules (CAMs), which mimics the strategy of leukocytes to adhere and traverse the vascular endothelium. Yet, the implications of this strategy on intracellular transport and in vivo biodistribution remain uncharacterized. We examined this using nanocarriers functionalized for dual- or triple-targeting to intercellular, platelet-endothelial, and/or vascular CAMs (ICAM-1, PECAM-1, VCAM-1). These molecules differ in expression level, location, pathological stimulation, and/or endocytic pathway. In endothelial cells, binding of PECAM-1/VCAM-1-targeted nanocarriers was intermediate to single-targeted counterparts and enhanced in disease-like conditions. ICAM-1/PECAM-1-targeted nanocarriers surpassed PECAM-1/VCAM-1 in control, but showed lower selectivity toward disease-like conditions. Triple-targeting resulted in binding similar to ICAM-1/PECAM-1 combination and displayed the highest selectivity in disease-like conditions. All combinations were effectively internalized by the cells, with slightly better performance when targeting receptors of different endocytic pathways. In vivo, ICAM-1/PECAM-1-targeted nanocarriers outperformed PECAM-1/VCAM-1 in control and disease-like conditions, and triple-targeted counterparts slightly enhanced this outcome in some organs. As a result, delivery of a model therapeutic cargo (acid sphingomyelinase, deficient in Niemann-Pick disease A-B) was enhanced to all affected organs by triple-targeted nanocarriers, particularly in disease-like conditions. Therefore, multi-CAM targeting

  17. Isolated palatal weakness without optic neuritis as the presenting manifestation of multiple sclerosis and its diagnostic dilemma with acute disseminated encephalomyelitis in a young boy.

    Science.gov (United States)

    Shah, Virti D; Mirgh, Sumeet Prakash; Surya, Nirmal

    2017-01-01

    We present a case of a young boy who at initial presentation was diagnosed as acute disseminated encephalomyelitis (ADEM) but subsequently on follow-up was diagnosed as multiple sclerosis (MS). Differentiating ADEM from MS in their first presentation can be tricky as the features may not be typical of anyone. The importance lies in the close follow-up of these patients.

  18. Cross-diagnostic validity of the SF-36 physical functioning scale in patients with stroke, multiple sclerosis and amyotrophic lateral sclerosis: a study using Rasch analysis

    NARCIS (Netherlands)

    Dallmeijer, Annet J.; de Groot, Vincent; Roorda, Leo D.; Schepers, Vera P. M.; Lindeman, Eline; van den Berg, Leonard H.; Beelen, Anita; Dekker, Joost

    2007-01-01

    The aim of this study was to investigate unidimensionality and differential item functioning of the SF-36 physical functioning scale (PF10) in patients with various neurological disorders. Patients: Patients post-stroke (n = 198), with multiple sclerosis (n = 151) and amyotrophic lateral sclerosis

  19. Combined effects of ULF, VLF, and EMIC Waves, Substorms, and Solar Wind Parameters on Relativistic Electron Flux: Multiple Regression Analysis

    Science.gov (United States)

    Simms, L. E.; Engebretson, M. J.; Rodger, C. J.; Gjerloev, J. W.; Lessard, M.; Clilverd, M. A.; Pilipenko, V.; Reeves, G. D.

    2016-12-01

    Relativistic electron flux may be influenced by energy inputs from the solar wind (velocity, number density, and IMF Bz), substorm activity, source and seed electron populations (tens of keV and hundreds of keV, respectively), as well as by the ULF, VLF, and EMIC waves triggered by these factors. As all these variables are intercorrelated, we use multiple regression analyses to determine which are most influential when other factors are controlled. For the years 2005-2011, we use daily averages of LANL geostationary orbit electron data (three high energy channels, as well as source and seed electrons), number of substorms per day from the SUPERMAG substorm list, a ULF index from ground magnetometers, lower band whistler mode chorus power (VLF) observed by the DEMETER satellite, and EMIC (support several hypotheses. ULF and VLF waves enhance the 1.8-3.5 MeV electron flux but their effect falls off (or becomes negative) on higher energy fluxes (3.5-6.0 and 6.0-7.8 MeV). EMIC waves reduce high energy electron flux mainly in the highest energy channel (6.0-7.8 MeV); their effect on the lower 1.8-3.5 MeV channel is minimal. A higher number of substorms in a day also enhance relativistic electron flux, with more impact at higher energy channels. We explore the relations between these parameters using path analysis to determine the mechanisms driving wave power which subsequently impact flux levels. We also assess the predictive ability of these models in forecasting flux.

  20. Diagnostic capacity for viral haemorrhagic septicaemia virus (VHSV) infection in rainbow trout (Oncorhynchus mykiss) is greatly increased by combining viral isolation with specific antibody detection

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Ariel, Ellen; Korsholm, H.

    2012-01-01

    Detection of disease specific antibodies in farmed rainbow trout (Oncorhynchus mykiss) has been proposed as an alternative or supplement to the currently approved procedures for diagnosis and surveillance in this species. In samples from natural outbreaks of the disease viral haemorrhagic...... septicaemia (VHS) at two freshwater farms in southern Denmark serologic testing was used to broaden the diagnostic window from outbreak to diagnosis in the laboratory as compared to traditional procedures of isolation and identification of the virus. The serologic assay clearly increased the chance...

  1. Combination of robot-assisted and conventional body-weight-supported treadmill training improves gait in persons with multiple sclerosis: a pilot study.

    Science.gov (United States)

    Ruiz, Jennifer; Labas, Michele P; Triche, Elizabeth W; Lo, Albert C

    2013-12-01

    The majority of persons with multiple sclerosis (MS) experience problems with gait, which they characterize as highly disabling impairments that adversely impact their quality of life. Thus, it is crucial to develop effective therapies to improve mobility for these individuals. The purpose of this study was to determine whether combination gait training, using robot-assisted treadmill training followed by conventional body-weight-supported treadmill training within the same session, improved gait and balance in individuals with MS. This study tested combination gait training in 7 persons with MS. The participants were randomized into the immediate therapy group (IT group) or the delayed therapy group (DT group). In phase I of the trial, the IT group received treatment while the DT group served as a concurrent comparison group. In phase II of the trial, the DT group received treatment identical to the treatment received by the IT group in phase I. Outcome measures included the 6-Minute Walk Test (6MWT), the Timed 25-Foot Walk Test, velocity, cadence, and the Functional Reach Test (FRT). Nonparametric statistical techniques were used for analysis. Combination gait training resulted in significantly greater improvements in the 6MWT for the IT group (median change = +59 m) compared with Phase I DT group (median change = -8 m) (P = 0.08) and FRT (median change = +3.3 cm in IT vs -0.8 cm in the DT group phase I; P = 0.03). Significant overall pre-post improvements following combination gait training were found in 6MWT (+32 m; P = 0.02) and FRT (+3.3 cm; P = 0.06) for IT and Phase II DT groups combined. Combination of robot with body-weight-supported treadmill training gait training is feasible and improved 6MWT and FRT distances in persons with MS.Video Abstract available (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A62) for more insights from the authors.

  2. Increasing the Fine Flaky Graphite Recovery in Flotation via a Combined MultipleTreatments Technique of Middlings

    Directory of Open Access Journals (Sweden)

    Weijun Peng

    2017-11-01

    Full Text Available As the residual flaky graphite ores become miscellaneous and fine, a single treatment technique for the middlings from the flotation process of graphite ore cannot efficiently recover the valuable graphite in the multistage grinding-flotation technology. In the study, the existence form of graphite and relationship of graphite with the associated gangue minerals were estimated by optical microscope analysis. The results indicated that the fine flaky graphite particles embedded with gangue minerals like a honeycomb, making it difficult to be beneficiated using the typical flotation technique. A combination technique of individual process and concentrated returning for the treatment of middlings was used to increase the graphite recovery based on the co-existing relationship between graphite and gangue minerals in the middlings. The graphite recovery of the final concentrate upgraded from 51.81% to 91.14% at a fixed carbon (FC content of 92.01% by a beneficiation process consisted of once coarse (94.41% passing 74 μm and rougher, five stages regrinding and six stages cleaning. The proposed treatment technique for middlings is of great significance to increase the recovery of fine flaky graphite.

  3. Combining Multiple Hypothesis Testing with Machine Learning Increases the Statistical Power of Genome-wide Association Studies

    Science.gov (United States)

    Mieth, Bettina; Kloft, Marius; Rodríguez, Juan Antonio; Sonnenburg, Sören; Vobruba, Robin; Morcillo-Suárez, Carlos; Farré, Xavier; Marigorta, Urko M.; Fehr, Ernst; Dickhaus, Thorsten; Blanchard, Gilles; Schunk, Daniel; Navarro, Arcadi; Müller, Klaus-Robert

    2016-01-01

    The standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008–2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0. PMID:27892471

  4. Combination chemotherapy for metastatic breast carcinoma. Prospective comparison of multiple drug therapy with L-phenylalanine mustard.

    Science.gov (United States)

    Canellos, G P; Pocock, S J; Taylor, S G; Sears, M E; Klaasen, D J; Band, P R

    1976-11-01

    A prospective randomized clinical trial was undertaken in 184 patients with metastatic breast carcinoma to compare single drug chemotherapy with L-phenylalanine mustard (L-PAM) and intermittent combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluourouracil (CMF). All patients had not been previously treated with cytotoxic drugs and all had objectively measurable visceral of soft tissue disease. Of the 93 patients who received CMF, 49 (53%) achieved a complete (14 patients) or partial (35 patients) regression of measurable tumor, for a median duration of 25 weeks. Eighteen of the 91 patients (20%) treated with L-PAM responded, for a median duration of 13 weeks. The toxicity was primarily hematologic, and greater in the CMF group, which also received more cycles of therapy because of the higher rate and duration of response. The overall survival of CMF-treated patients was superior to that of the single drug group. The differences were even greater when the patients were subclassified according to the presence of liver involvement or nonambulatory performance status. The superior antitumor effect of CMF over L-PAM suggests that it may be a more effective drug regimen to be used as an adjuvant to primary therapy.

  5. Hybrid approach combining multiple characterization techniques and simulations for microstructural analysis of proton exchange membrane fuel cell electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Cetinbas, Firat C.; Ahluwalia, Rajesh K.; Kariuki, Nancy; De Andrade, Vincent; Fongalland, Dash; Smith, Linda; Sharman, Jonathan; Ferreira, Paulo; Rasouli, Somaye; Myers, Deborah J.

    2017-03-01

    The cost and performance of proton exchange membrane fuel cells strongly depend on the cathode electrode due to usage of expensive platinum (Pt) group metal catalyst and sluggish reaction kinetics. Development of low Pt content high performance cathodes requires comprehensive understanding of the electrode microstructure. In this study, a new approach is presented to characterize the detailed cathode electrode microstructure from nm to μm length scales by combining information from different experimental techniques. In this context, nano-scale X-ray computed tomography (nano-CT) is performed to extract the secondary pore space of the electrode. Transmission electron microscopy (TEM) is employed to determine primary C particle and Pt particle size distributions. X-ray scattering, with its ability to provide size distributions of orders of magnitude more particles than TEM, is used to confirm the TEM-determined size distributions. The number of primary pores that cannot be resolved by nano-CT is approximated using mercury intrusion porosimetry. An algorithm is developed to incorporate all these experimental data in one geometric representation. Upon validation of pore size distribution against gas adsorption and mercury intrusion porosimetry data, reconstructed ionomer size distribution is reported. In addition, transport related characteristics and effective properties are computed by performing simulations on the hybrid microstructure.

  6. Combining Multiple Hypothesis Testing with Machine Learning Increases the Statistical Power of Genome-wide Association Studies

    Science.gov (United States)

    Mieth, Bettina; Kloft, Marius; Rodríguez, Juan Antonio; Sonnenburg, Sören; Vobruba, Robin; Morcillo-Suárez, Carlos; Farré, Xavier; Marigorta, Urko M.; Fehr, Ernst; Dickhaus, Thorsten; Blanchard, Gilles; Schunk, Daniel; Navarro, Arcadi; Müller, Klaus-Robert

    2016-11-01

    The standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008-2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0.

  7. Comparison of a skin-lightening cream targeting melanogenesis on multiple levels to triple combination cream for melasma.

    Science.gov (United States)

    Monheit, Gary D; Dreher, Frank

    2013-03-01

    The safety and efficacy of a novel skin-lightening cream (SLC) with 4% hydroquinone (HQ), which additionally contains 4 skin-brightening actives, was compared with a triple combination cream (TCC) with 4% HQ, 0.05% tretinoin, and 0.01% fluocinolone acetonide for the treatment of melasma under measures of sun protection. The study was a randomized, investigator-blinded, split-face study including 20 Caucasian females with at least mild epidermal or mixed melasma. Evaluations were made before treatment, after 4 and 8 weeks, and after 12 weeks at the end of the once-daily treatment period with the creams. The evaluations included the investigator's tolerability assessments, the Investigator's Global Assessment, the Melasma Area and Severity Index (MASI), and a participant questionnaire. Under the conditions of the present study, the SLC was comparable in both efficacy and tolerability with the well-established TCC treatment for facial melasma. The MASI reduction became significant for both creams after 4 weeks and reached -77% for SLC and -79% for TCC cream after 12 weeks of once-daily use under measures of sun protection. None of the subjects discontinued treatment because of an intolerability or adverse event. About one-third of the subjects experienced at least one local intolerability (eg, erythema, dryness, or peeling) with both creams over the entire study period, while the remaining subjects did not experience any intolerabilities.

  8. Doppler Impedance Changes at the Fetal Brain Vessels in a Pregnancy Affected with a Multiple Combination of Uteroplacental Anomalies

    Directory of Open Access Journals (Sweden)

    José Morales-Roselló

    2012-01-01

    Full Text Available A fetus with a very rare five-fold combination of uteroplacental anomalies, bicornuate uterus, short cervix with cervical incompetence, multilobed placenta succenturiata, accessory cotyledon within the cervical funneling, and umbilical cord insertion into the anomalous cervical cotyledon, presented an early and marked decrease at the vertebral and middle cerebral arteries Doppler resistances. This cerebral low-impedance state, usually found before labor, and considered an adaptive mechanism developed to protect the fetus at term from labor asphyxia, was present for an unknown reason at 20 weeks. After the patient was treated with vaginal progesterone, the cervix shortening improved and markedly, at the same time, the cerebral vascular resistances increased and maintained an adequate for gestational age impedance until delivery at 34 weeks. As the described uteroplacental anomalies determined a high risk of preterm delivery, due to cervical dilation, cord compresion, and placental haemorrhage, these fluctuating brain vascular changes might be the result of the fetal adaptation to the changes preceding an imminent delivery.

  9. Predicting siRNA efficacy based on multiple selective siRNA representations and their combination at score level

    Science.gov (United States)

    He, Fei; Han, Ye; Gong, Jianting; Song, Jiazhi; Wang, Han; Li, Yanwen

    2017-03-01

    Small interfering RNAs (siRNAs) may induce to targeted gene knockdown, and the gene silencing effectiveness relies on the efficacy of the siRNA. Therefore, the task of this paper is to construct an effective siRNA prediction method. In our work, we try to describe siRNA from both quantitative and qualitative aspects. For quantitative analyses, we form four groups of effective features, including nucleotide frequencies, thermodynamic stability profile, thermodynamic of siRNA-mRNA interaction, and mRNA related features, as a new mixed representation, in which thermodynamic of siRNA-mRNA interaction is introduced to siRNA efficacy prediction for the first time to our best knowledge. And then an F-score based feature selection is employed to investigate the contribution of each feature and remove the weak relevant features. Meanwhile, we encode the siRNA sequence and existed empirical design rules as a qualitative siRNA representation. These two kinds of siRNA representations are combined to predict siRNA efficacy by supported Vector Regression (SVR) at score level. The experimental results indicate that our method may select the features with powerful discriminative ability and make the two kinds of siRNA representations work at full capacity. The prediction results also demonstrate that our method can outperform other popular siRNA efficacy prediction algorithms.

  10. The current and future state of companion diagnostics

    Directory of Open Access Journals (Sweden)

    Agarwal A

    2015-03-01

    Full Text Available Amit Agarwal,1 Dan Ressler,2 Glenn Snyder1 1Deloitte Consulting LLP, San Francisco, CA, USA; 2Deloitte Consulting LLP, Philadelphia, PA, USA Abstract: Companion diagnostics are an indispensable part of personalized medicine and will likely continue to rapidly increase in number and application to disease areas. The first companion diagnostics were launched in the 1980s and in the face of significant initial skepticism from drug developers as to whether segmenting a drug's market through a diagnostic was advisable. The commercial success of drugs such as Herceptin® (trastuzumab and Gleevec® (imatinib, which both require testing with companion diagnostics before they can be prescribed, has moved the entire companion diagnostic field forward. From an initial start of a handful of oncology drugs with corresponding diagnostics, the field has expanded to include multiple therapeutic areas, and the number of combinations has grown by 12-fold. Based on drugs in clinical trials, the rapid growth will likely continue for the foreseeable future. This expansion of companion diagnostics will also have a global component as markets in Europe will evolve in a similar but not identical pattern as the US. One of the greatest challenges to future growth in companion diagnostics is aligning the incentives of all stakeholders. A major driver of growth will continue to be the economic incentives for drug developers to pair their products with diagnostics. However, diagnostic companies are caught between the conflicting demands of two major stakeholders, pharmaceutical companies on one hand and payers/providers on the other. Regulators are also becoming more demanding in aligning development time lines between drugs and diagnostics. In order to survive and prosper, diagnostic companies will need to think more broadly about companion diagnostics than the historical match between a specific drug and a single diagnostic. They will also have to continue the process of

  11. Combining multiple autosomal introns for studying shallow phylogeny and taxonomy of Laurasiatherian mammals: Application to the tribe Bovini (Cetartiodactyla, Bovidae).

    Science.gov (United States)

    Hassanin, Alexandre; An, Junghwa; Ropiquet, Anne; Nguyen, Trung Thanh; Couloux, Arnaud

    2013-03-01

    Mitochondrial sequences are widely used for species identification and for studying phylogenetic relationships among closely related species or populations of the same species. However, many studies of mammals have shown that the maternal history of the mitochondrial genome can be discordant with the true evolutionary history of the taxa. In such cases, the analyses of multiple nuclear genes can be more powerful for deciphering interspecific relationships. Here, we designed primers for amplifying 13 new exon-primed intron-crossing (EPIC) autosomal loci for studying shallow phylogeny and taxonomy of Laurasiatherian mammals. Three criteria were used for the selection of the markers: gene orthology, a PCR product length between 600 and 1200 nucleotides, and different chromosomal locations in the bovine genome. Positive PCRs were obtained from different species representing the orders Carnivora, Cetartiodactyla, Chiroptera, Perissodactyla and Pholidota. The newly developed markers were analyzed in a phylogenetic study of the tribe Bovini (the group containing domestic and wild cattle, bison, yak, African buffalo, Asian buffalo, and saola) based on 17 taxa and 18 nuclear genes, representing a total alignment of 13,095 nucleotides. The phylogenetic results were compared to those obtained from analyses of the complete mitochondrial genome and Y chromosomal genes. Our analyses support a basal divergence of the saola (Pseudoryx) and a sister-group relationship between yak and bison. These results contrast with recent molecular studies but are in better agreement with morphology. The comparison of pairwise nucleotide distances shows that our nuDNA dataset provides a good signal for identifying taxonomic levels, such as species, genera, subtribes, tribes and subfamilies, whereas the mtDNA genome fails because of mtDNA introgression and higher levels of homoplasy. Accordingly, we conclude that the genus Bison should be regarded as a synonym of Bos, with the European bison

  12. The strategy for establishment of the multiple reaction monitoring based characteristic chemical profile of triterpenes in Alismatis rhizoma using two combined tandem mass spectrometers.

    Science.gov (United States)

    Li, Sen; Jin, Shuna; Song, Chengwu; Jia, Shuailong; Zhang, Yang; Feng, Yulin; Du, Zhifeng; Jiang, Hongliang

    2017-11-17

    It was reported that triterpenes compounds in Alismatis rhizoma (AR) contributed to the lipid lowering effect on high fat diet (HFD)-induced hyperlipidemia. To date only 24 triterpenes (including the isomers) were characterized by LC-QTOF-MS/MS due to the lack of strategies for systematic discovery, classification and identification of triterpenes in AR. In this study, an integrated strategy combining various QTOF-MS/MS and QTRAP-MS/MS scan functions was developed for systematic identification and specific characterization of triterpenes in AR and processed AR. First, MS/MS fragmentation behaviors of different types of triterpenes were investigated and their diagnostic product ions were systematically summarized for discovery and classification of triterpenes. Second, diagnostic product ions were used to filter the data acquired by UHPLC-QTOF MS/MS for efficient identification of targeted triterpenes. Third, MRM-based characteristic chemical profile (CCP) of triterpenes was established using 30 MRM transitions by UHPLC-QTRAP-MS/MS. Fourth, MRM-based CCP was applied for comparative analyses of triterpenes in AR from different regions and from two other processed AR (salt processed AR and bran processed AR). Consequently, a total of 80 triterpenes including 14 novel compounds were identified in the AR, and 7 more triterpenes compounds were discovered using MRM-based CCP in the processed AR. This work is the most comprehensive characterization of triterpenes compounds in AR to date. The established MRM-based CCP of triterpenes compounds can be instructive for qualitative analyses and relative quantitative analyses of triterpenes in AR and its related medicinal products for potential applications including quality control and classification of different AR materials. Copyright © 2017. Published by Elsevier B.V.

  13. Combined gene expression and proteomic analysis of EGF induced apoptosis in A431 cells suggests multiple pathways trigger apoptosis.

    Science.gov (United States)

    Alanazi, Ibrahim; Ebrahimie, Esmaeil; Hoffmann, Peter; Adelson, David L

    2013-11-01

    A431 cells, derived from epidermoid carcinoma, overexpress the epidermal growth factor receptor (EGFR) and when treated with a high dose of EGF will undergo apoptosis. We exploited microarray and proteomics techniques and network prediction to study the regulatory mechanisms of EGF-induced apoptosis in A431 cells. We observed significant changes in gene expression in 162 genes, approximately evenly split between pro-apoptotic and anti-apoptotic genes and identified 30 proteins from the proteomic data that had either pro or anti-apoptotic annotation. Our correlation analysis of gene expression and proteome modeled a number of distinct sub-networks that are associated with the onset of apoptosis, allowing us to identify specific pathways and components. These include components of the interferon signalling pathway, and down stream components, including cytokines and suppressors of cytokine signalling. A central component of almost all gene expression sub-networks identified was TP53, which is mutated in A431 cells, and was down regulated. This down regulation of TP53 appeared to be correlated with proteomic sub-networks of cytoskeletal or cell adhesion components that might induce apoptosis by triggering cytochrome C release. Of the only three genes also differentially expressed as proteins, only serpinb1 had a known association with apoptosis. We confirmed that up regulation and cleavage of serpinb1 into L-DNAaseII was correlated with the induction of apoptosis. It is unlikely that a single pathway, but more likely a combination of pathways is needed to trigger EGF induced apoptosis in A431cells.

  14. [A Case of HER2-Positive Advanced Gastric Cancer with Multiple Liver Metastases Effectively Treated with Trastuzumab, Capecitabine, and Cisplatin Combination Therapy].

    Science.gov (United States)

    Kuga, Yoshio; Kitamura, Shosuke; Okanobu, Hideharu; Sakimoto, Hideto; Nishida, Toshihiro

    2016-10-01

    We reported a case of human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer with multiple liver metastases that responded well to a combination of trastuzumab, capecitabine, and cisplatin(T-XP therapy)as first-line chemotherapy. A 73-year-old man was admitted to our hospital in December 2012 for liver dysfunction. Based on computed tomography(CT)and gastroendoscopy findings, he was diagnosed with advanced gastric cancer with multiple liver metastases. Because HER2 protein overexpression was observed in the primary tumor, he was treated with T-XP therapy. After 5 courses of treatment, the sizes of the primary tumor and multiple liver metastases were reduced on CT scans. In March 2013, a Billroth I distal gastrectomy with D2 lymph node dissection was performed. Liver metastasis was not detected. No residual cancer cells were found in the stomach or lymph nodes. The patient subsequently received oral administration of S-1 alone for 2 weeks followed by a 2-week rest period as 1 course. This was repeated for 19 courses. The postoperative course was uneventful, and there was no detectable liver metastasis 36 months after the original diagnosis. Therefore, T-XP therapy is an option for the management of HER2-positive advanced gastric cancer with liver metastasis.

  15. Analysis of gene expression profiles of soft tissue sarcoma using a combination of knowledge-based filtering with integration of multiple statistics.

    Science.gov (United States)

    Takahashi, Anna; Nakayama, Robert; Ishibashi, Nanako; Doi, Ayano; Ichinohe, Risa; Ikuyo, Yoriko; Takahashi, Teruyoshi; Marui, Shigetaka; Yasuhara, Koji; Nakamura, Tetsuro; Sugita, Shintaro; Sakamoto, Hiromi; Yoshida, Teruhiko; Hasegawa, Tadashi; Takahashi, Hiro

    2014-01-01

    The diagnosis and treatment of soft tissue sarcomas (STS) have been difficult. Of the diverse histological subtypes, undifferentiated pleomorphic sarcoma (UPS) is particularly difficult to diagnose accurately, and its classification per se is still controversial. Recent advances in genomic technologies provide an excellent way to address such problems. However, it is often difficult, if not impossible, to identify definitive disease-associated genes using genome-wide analysis alone, primarily because of multiple testing problems. In the present study, we analyzed microarray data from 88 STS patients using a combination method that used knowledge-based filtering and a simulation based on the integration of multiple statistics to reduce multiple testing problems. We identified 25 genes, including hypoxia-related genes (e.g., MIF, SCD1, P4HA1, ENO1, and STAT1) and cell cycle- and DNA repair-related genes (e.g., TACC3, PRDX1, PRKDC, and H2AFY). These genes showed significant differential expression among histological subtypes, including UPS, and showed associations with overall survival. STAT1 showed a strong association with overall survival in UPS patients (logrank p = 1.84 × 10(-6) and adjusted p value 2.99 × 10(-3) after the permutation test). According to the literature, the 25 genes selected are useful not only as markers of differential diagnosis but also as prognostic/predictive markers and/or therapeutic targets for STS. Our combination method can identify genes that are potential prognostic/predictive factors and/or therapeutic targets in STS and possibly in other cancers. These disease-associated genes deserve further preclinical and clinical validation.

  16. Application du problème de caractérisation multiple à la conception de tests de diagnostic pour la biologie végétale

    OpenAIRE

    Chhel, Fabien; Lardeux, Frédéric; Saubion, Frédéric; Zanuttini, Bruno

    2013-01-01

    National audience; In this paper, we address a characterization problem coming from plant biology. The multiple characterization problem consists of entities (represented by Boolean assignments) belonging to several groups, and the goal is to find a characterization for each group using propositional logic. This characterization must be exact and the main difficulty is to compute the minimal one. We show that this problem is W[2]-Complete. We also propose a reformulation to a linear program a...

  17. Combining multiple measurement and isotope techniques to help target erosion hot-spots in the Great Barrier Reef catchments

    Science.gov (United States)

    Bartley, Rebecca; Croke, Jacky; Bainbridge, Zoe; Wilkinson, Scott; Hancock, Gary; Austin, Jen; Kuhnert, Petra

    2016-04-01

    There is considerable evidence that the amount of sediment reaching the Great Barrier Reef (GBR), Australia, has increased since agricultural development commenced in the 1870's. This is having deleterious effects on freshwater and marine ecosystems. However, understanding the primary source and processes driving the increased sediment delivery has been challenging due to the large size and hydrogeomorphic diversity of adjacent catchments. This paper presents the results from several projects that employed a diverse range of measurement techniques all aimed at understanding the spatial and temporal changes in sediment yield from the 130,000 km2 Burdekin catchment, Australia. Cosmogenic nuclides (10Be) were combined with contemporary sediment flux monitoring to help identify high risk sub-catchments that have anthropogenically accelerated erosion. Within the sub-catchments, fallout radionuclides (137Cs, 7Pb and 7Be) were uses to determine the dominant erosion process (surface vs sub-surface erosion). Long term monitoring of improved grazing land management (using nested flumes and gauges), were used to evaluate the effectiveness of land management changes on sediment yields at paddock and catchment scales over 10 years. The results suggest that the Bowen and Upper Burdekin sub-catchments are the dominant anthropogenic source of sediment to the GBR having an accelerated erosion factor of 7.47 (± 3.71) and 3.64 (± 0.5), respectively. Within these sub-catchments, most of the fine sediment is coming from vertical channel walls (50%) or horizontal sub-surface soils (~42%). Remediating these catchments and reducing sediment delivery is likely to take greater than 10 years, and will require a range of approaches including pasture and rangeland management, as well as targeted erosion control in highly gullied landscapes. Together, these data sets help elucidate the often complex sediment delivery processes to the GBR. This helps policy and management determine where to

  18. Cable Diagnostic Focused Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Hartlein, R.A.; Hampton, R.N.

    2010-12-30

    This report summarizes an extensive effort made to understand how to effectively use the various diagnostic technologies to establish the condition of medium voltage underground cable circuits. These circuits make up an extensive portion of the electric delivery infrastructure in the United States. Much of this infrastructure is old and experiencing unacceptable failure rates. By deploying efficient diagnostic testing programs, electric utilities can replace or repair circuits that are about to fail, providing an optimal approach to improving electric system reliability. This is an intrinsically complex topic. Underground cable systems are not homogeneous. Cable circuits often contain multiple branches with different cable designs and a range of insulation materials. In addition, each insulation material ages differently as a function of time, temperature and operating environment. To complicate matters further, there are a wide variety of diagnostic technologies available for assessing the condition of cable circuits with a diversity of claims about the effectiveness of each approach. As a result, the benefits of deploying cable diagnostic testing programs have been difficult to establish, leading many utilities to avoid the their use altogether. This project was designed to help address these issues. The information provided is the result of a collaborative effort between Georgia Tech NEETRAC staff, Georgia Tech academic faculty, electric utility industry participants, as well as cable system diagnostic testing service providers and test equipment providers. Report topics include: •How cable systems age and fail, •The various technologies available for detecting potential failure sites, •The advantages and disadvantages of different diagnostic technologies, •Different approaches for utilities to employ cable system diagnostics. The primary deliverables of this project are this report, a Cable Diagnostic Handbook (a subset of this report) and an online

  19. Effectiveness of a combination of ezetimibe and statins in patients with acute coronary syndrome and multiple comorbidities: A 6-year population-based cohort study.

    Science.gov (United States)

    Lin Wu, Fe-Lin; Wang, Jui; Ho, Wei; Chou, Chia-Hung; Wu, Yi-Jung; Choo, Dan-Wei; Wang, Yu-Wen; Chen, Po-Yu; Chien, Kuo-Liong; Lin, Zhen-Fang

    2017-04-15

    The clinical benefits of a combination of statins and ezetimibe in patients with acute coronary syndrome (ACS) were observed in a clinical trial. However, little is known regarding the effectiveness of using statins with or without ezetimibe in patients with ACS and multiple comorbidities in real-world clinical practice. This is a nationwide population-based cohort study using Taiwan National Health Insurance Research Database. A total of 212,110 patients with ACS who had been discharged after their first ACS events between 2006 and 2010 were enrolled. A propensity score matching approach was used to create matched cohorts for adjusting potential confounders. Cox proportional hazards regressions were performed to estimate the risk of re-hospitalization for ACS and revascularization. Patients in the statins-plus-ezetimibe group had a significantly lower risk of re-hospitalization for ACS (adjusted hazard ratio [HR]=0.64, 95% confidence interval [CI]: 0.60-0.69) and revascularization (HR=0.69, 95% CI: 0.63-0.76) than those in the statins-alone group. In the statins-plus-ezetimibe group, female patients had a lower risk of re-hospitalization for ACS than male patients did, and patients without diabetes mellitus had a lower risk of re-hospitalization for ACS than did patients with diabetes mellitus. Patients with ACS and multiple comorbidities receiving a combination therapy of statins and ezetimibe had a lower risk of re-hospitalization for ACS and revascularization than those receiving statins alone. Significant interaction effects were observed between combination with ezetimibe, sex, and diabetes mellitus. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The discordance rate, a new concept for combining diagnostic decisions with analytical performance characteristics. 2. Defining analytical goals applied to the diagnosis of type 2 diabetes by blood glucose concentrations.

    Science.gov (United States)

    Haeckel, Rainer; Wosniok, Werner

    2004-02-01

    A novel statistical approach has recently been described to estimate diagnostic "errors" in method comparison studies. This procedure requires a population-based probability, pp, which describes the spread of values within the population under study, and an analytical probability, Pa, quantifying the risk of errors at a decision limit due to replacing one method by the other. The population probability was derived from 207 subjects who were submitted to an oral glucose tolerance test due to suspicion of type 2 diabetes. The new concept was then applied in a reverse mode by determining the analytical variability of glucose concentrations for a fixed discordance rate diagnosing type 2 diabetes. If a combined discordance rate (sum of positive and negative discordances) of 5% is allowed, a maximal imprecision of 3.7% can be tolerated in the absence of bias. In the presence of a 3.0% bias, the allowable imprecision must be reduced to 2.8%. The relationship between bias and imprecision followed a complex function and not a simple linear model. These allowable limits were achieved with venous plasma in the fasting state. The allowable analytical specifications were slightly more stringent with capillary blood. After a 2 h glucose challenge, higher error rates could be tolerated, indicating that post-load glucose concentrations have a higher diagnostic efficiency than fasting levels. The new concept has the advantage that it is derived from patient's samples in relation to diagnostic requirements.

  1. Diagnostic and therapeutic evaluation of multiple choroidal granulomas in a patient with confirmed sarcoidosis using enhanced depth imaging optical coherence tomography.

    Science.gov (United States)

    Ishihara, Mami; Shibuya, Etsuko; Tanaka, Shin; Mizuki, Nobuhisa

    2017-10-05

    Sarcoidosis is a major cause of granulomatous uveitis but rarely manifests as multiple choroidal granulomas. This report describes the use of enhanced depth imaging optical coherence tomography (EDI-OCT) to visualize changes occurring in multiple choroidal granulomas during treatment. The patient was a 36-year-old Japanese man with histopathologically confirmed sarcoidosis, who was examined using EDI-OCT and showed multiple yellowish-white subretinal lesions in the peripapillary region and the arcade of the right eye. EDI-OCT revealed homogeneous hyporeflective choroidal lesions with choriocapillaris thinning, consistent with a diagnosis of choroidal granulomas. Subretinal fluid adjacent to one of the peripapillary choroidal lesions was also apparent. EDI-OCT during oral prednisolone administration revealed a decrease in lesion size at as early as 3 weeks and complete resolution of the lesions after 6 months of treatment. However, 2 months after prednisolone discontinuation, EDI-OCT revealed recurrence of choroidal granulomas in the peripapillary region and the arcade of the right eye. After injection of triamcinolone acetonide into the posterior sub-Tenon's capsule (sub-Tenon's injection), EDI-OCT demonstrated a reduction in granuloma lesion size within 3 months of the injection. EDI-OCT allowed detailed morphologic visualization of the choroidal granulomas caused by sarcoidosis. This imaging technique was useful for monitoring changes in granuloma size in response to steroid administration and for early detection of recurrence. Injection of triamcinolone acetonide into the posterior sub-Tenon's capsule was as effective as oral prednisolone for the treatment of choroidal granulomas.

  2. Diagnostic accuracy of 256-row multidetector CT coronary angiography with prospective ECG-gating combined with fourth-generation iterative reconstruction algorithm in the assessment of coronary artery bypass: evaluation of dose reduction and image quality.

    Science.gov (United States)

    Ippolito, Davide; Fior, Davide; Franzesi, Cammillo Talei; Riva, Luca; Casiraghi, Alessandra; Sironi, Sandro

    2017-08-28

    Effective radiation dose in coronary CT angiography (CTCA) for coronary artery bypass graft (CABG) evaluation is remarkably high because of long scan lengths. Prospective electrocardiographic gating with iterative reconstruction can reduce effective radiation dose. To evaluate the diagnostic performance of low-kV CT angiography protocol with prospective ecg-gating technique and iterative reconstruction (IR) algorithm in follow-up of CABG patients compared with standard retrospective protocol. Seventy-four non-obese patients with known coronary disease treated with artery bypass grafting were prospectively enrolled. All the patients underwent 256 MDCT (Brilliance iCT, Philips) CTCA using low-dose protocol (100 kV; 800 mAs; rotation time: 0.275 s) combined with prospective ECG-triggering acquisition and fourth-generation IR technique (iDose(4); Philips); all the lengths of the bypass graft were included in the evaluation. A control group of 42 similar patients was evaluated with a standard retrospective ECG-gated CTCA (100 kV; 800 mAs).On both CT examinations, ROIs were placed to calculate standard deviation of pixel values and intra-vessel density. Diagnostic quality was also evaluated using a 4-point quality scale. Despite the statistically significant reduction of radiation dose evaluated with DLP (study group mean DLP: 274 mGy cm; control group mean DLP: 1224 mGy cm; P value evaluated by two radiologists in "double blind", did not reveal any significant difference in diagnostic quality of the two groups. The development of high-speed MDCT scans combined with modern IR allows an accurate evaluation of CABG with prospective ECG-gating protocols in a single breath hold, obtaining a significant reduction in radiation dose.

  3. Video integrated measurement system. [Diagnostic display devices

    Energy Technology Data Exchange (ETDEWEB)

    Spector, B.; Eilbert, L.; Finando, S.; Fukuda, F.

    1982-06-01

    A Video Integrated Measurement (VIM) System is described which incorporates the use of various noninvasive diagnostic procedures (moire contourography, electromyography, posturometry, infrared thermography, etc.), used individually or in combination, for the evaluation of neuromusculoskeletal and other disorders and their management with biofeedback and other therapeutic procedures. The system provides for measuring individual diagnostic and therapeutic modes, or multiple modes by split screen superimposition, of real time (actual) images of the patient and idealized (ideal-normal) models on a video monitor, along with analog and digital data, graphics, color, and other transduced symbolic information. It is concluded that this system provides an innovative and efficient method by which the therapist and patient can interact in biofeedback training/learning processes and holds considerable promise for more effective measurement and treatment of a wide variety of physical and behavioral disorders.

  4. Diagnostic significance of the newest biomarkers of steatosis progression in patients with stable coronary heart disease, combined with nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    I. I. Vakalyuk

    2018-03-01

    Full Text Available The purpose was to determine the diagnostic value of selenoprotein P and M30 fragments of cytokeratin 18 in conjunction with proinflammatory cytokines for early diagnosis and progression of non-alcoholic fatty liver disease (NAFLD in patients with stable coronary heart disease (CHD. Materials and methods. 140 patients with NAFLD and stable CHD of II-III functional classes were examined: 89 patients with non-alcoholic steatosis (Group I; 51 patients with non-alcoholic steatohepatitis (Group II. General-clinical examination, electrocardiography, coronary angiography, echocardiography, liver ultrasound, determination of cytokeratin 18 M30, selenoprotein P, TNF-alpha, interleukin-6, high-sensitivity C-reactive protein serum levels were performed to all patients. Results. The presence of liver steatosis of different degrees was established in all examined patients. However, the majority of the patients of Group I had steatosis of 1 and 2 degrees; in group 2 – steatosis of 3 degree prevailed. Selenoprotein P level in patients with steatosis of 1 degree was on 39.6 % higher compared with 0 degree; at 2 degree – it was by 2.8 times higher vs. its level in the control group and by 1.9 times vs. its level at steatosis of 1 degree (P < 0.05. Cytokeratin 18 M30 level at steatosis of 1 degree was by 1.8 times higher than its value in the control group; at 2 degree – it exceed this value by 2.3 times; at 3 degree – it reached its highest value (P < 0.05. TNF-alpha level at 1 degree of steatosis was by 2.5 times higher than its value in the control group; at 2 degree – it exceed this value by 3.7 times; at 3 degree – it was by 5.4; 2.2 and 1.5 times higher vs. its value at steatosis 0, 1 and 2 degrees (P < 0.05. Similar patterns were observed by IL-6 and hsCRP levels. Positive correlation relationships between serum selenoprotein P, cytokeratin 18 M30 and proinflammatory cytokines levels were revealed. Conclusion. Increasing of serum selenoprotein

  5. Estimating Dbh of Trees Employing Multiple Linear Regression of the best Lidar-Derived Parameter Combination Automated in Python in a Natural Broadleaf Forest in the Philippines

    Science.gov (United States)

    Ibanez, C. A. G.; Carcellar, B. G., III; Paringit, E. C.; Argamosa, R. J. L.; Faelga, R. A. G.; Posilero, M. A. V.; Zaragosa, G. P.; Dimayacyac, N. A.

    2016-06-01

    Diameter-at-Breast-Height Estimation is a prerequisite in various allometric equations estimating important forestry indices like stem volume, basal area, biomass and carbon stock. LiDAR Technology has a means of directly obtaining different forest parameters, except DBH, from the behavior and characteristics of point cloud unique in different forest classes. Extensive tree inventory was done on a two-hectare established sample plot in Mt. Makiling, Laguna for a natural growth forest. Coordinates, height, and canopy cover were measured and types of species were identified to compare to LiDAR derivatives. Multiple linear regression was used to get LiDAR-derived DBH by integrating field-derived DBH and 27 LiDAR-derived parameters at 20m, 10m, and 5m grid resolutions. To know the best combination of parameters in DBH Estimation, all possible combinations of parameters were generated and automated using python scripts and additional regression related libraries such as Numpy, Scipy, and Scikit learn were used. The combination that yields the highest r-squared or coefficient of determination and lowest AIC (Akaike's Information Criterion) and BIC (Bayesian Information Criterion) was determined to be the best equation. The equation is at its best using 11 parameters at 10mgrid size and at of 0.604 r-squared, 154.04 AIC and 175.08 BIC. Combination of parameters may differ among forest classes for further studies. Additional statistical tests can be supplemented to help determine the correlation among parameters such as Kaiser- Meyer-Olkin (KMO) Coefficient and the Barlett's Test for Spherecity (BTS).

  6. ESTIMATING DBH OF TREES EMPLOYING MULTIPLE LINEAR REGRESSION OF THE BEST LIDAR-DERIVED PARAMETER COMBINATION AUTOMATED IN PYTHON IN A NATURAL BROADLEAF FOREST IN THE PHILIPPINES

    Directory of Open Access Journals (Sweden)

    C. A. G. Ibanez

    2016-06-01

    Full Text Available Diameter-at-Breast-Height Estimation is a prerequisite in various allometric equations estimating important forestry indices like stem volume, basal area, biomass and carbon stock. LiDAR Technology has a means of directly obtaining different forest parameters, except DBH, from the behavior and characteristics of point cloud unique in different forest classes. Extensive tree inventory was done on a two-hectare established sample plot in Mt. Makiling, Laguna for a natural growth forest. Coordinates, height, and canopy cover were measured and types of species were identified to compare to LiDAR derivatives. Multiple linear regression was used to get LiDAR-derived DBH by integrating field-derived DBH and 27 LiDAR-derived parameters at 20m, 10m, and 5m grid resolutions. To know the best combination of parameters in DBH Estimation, all possible combinations of parameters were generated and automated using python scripts and additional regression related libraries such as Numpy, Scipy, and Scikit learn were used. The combination that yields the highest r-squared or coefficient of determination and lowest AIC (Akaike’s Information Criterion and BIC (Bayesian Information Criterion was determined to be the best equation. The equation is at its best using 11 parameters at 10mgrid size and at of 0.604 r-squared, 154.04 AIC and 175.08 BIC. Combination of parameters may differ among forest classes for further studies. Additional statistical tests can be supplemented to help determine the correlation among parameters such as Kaiser- Meyer-Olkin (KMO Coefficient and the Barlett’s Test for Spherecity (BTS.

  7. A novel combination of multiple primary carcinomas: Urinary bladder transitional cell carcinoma, prostate adenocarcinoma and small cell lung carcinoma- report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Giannikaki Elpida

    2005-07-01

    Full Text Available Abstract Background The incidence of multiple primary malignant neoplasms increases with age and they are encountered more frequently nowadays than before, the phenomenon is still considered to be rare. Case presentation We report a case of a man in whom urinary bladder transitional cell carcinoma, metachronous prostate adenocarcinoma and small cell lung carcinoma were diagnosed within an eighteen-month period. The only known predisposing factor was that he was heavy smoker (90–100 packets per year. The literature on the phenomenon of multiple primary malignancies in a single patient is reviewed and the data is summarized. Conclusion It is important for the clinicians to keep in mind the possibility of a metachronous (successive or a synchronous (simultaneous malignancy in a cancer patient. It is worthy mentioning this case because clustering of three primary malignancies (synchronous and metachronous is of rare occurrence in a single patient, and, to our knowledge, this is the first report this combination of three carcinomas appearing in the same patient.

  8. A paradigm shift: Cancer therapy with peptide-based B-cell epitopes and peptide immunotherapeutics targeting multiple solid tumor types: Emerging concepts and validation of combination immunotherapy.

    Science.gov (United States)

    Kaumaya, Pravin T P

    2015-01-01

    There is a recognizable and urgent need to speed the development and application of novel, more efficacious anti-cancer vaccine therapies that inhibit tumor progression and prevent acquisition of tumor resistance. We have created and established a portfolio of validated peptide epitopes against multiple receptor tyrosine kinases and we have identified the most biologically effective combinations of EGFR (HER-1), HER-2, HER-3, VEGF and IGF-1R peptide vaccines/mimics to selectively inhibit multiple receptors and signaling pathways. The strategy is based on the use of chimeric conformational B-cell epitope peptides incorporating "promiscuous" T-cell epitopes that afford the possibility of generating an enduring immune response, eliciting protein-reactive high-affinity anti-peptide antibodies as potential vaccines and peptide mimics that act as antagonists to receptor signaling that drive cancer metastasis. In this review we will summarize our ongoing studies based on the development of combinatorial immunotherapeutic strategies that act synergistically to enhance immune-mediated tumor killing aimed at addressing mechanisms of tumor resistance for several tumor types.

  9. Six-band terahertz metamaterial absorber based on the combination of multiple-order responses of metallic patches in a dual-layer stacked resonance structure.

    Science.gov (United States)

    Wang, Ben-Xin; Wang, Gui-Zhen; Sang, Tian; Wang, Ling-Ling

    2017-01-25

    This paper reports on a numerical study of the six-band metamaterial absorber composed of two alternating stack of metallic-dielectric layers on top of a continuous metallic plane. Six obvious resonance peaks with high absorption performance (average larger than 99.37%) are realized. The first, third, fifth, and the second, fourth, sixth resonance absorption bands are attributed to the multiple-order responses (i.e., the 1-, 3- and 5-order responses) of the bottom- and top-layer of the structure, respectively, and thus the absorption mechanism of six-band absorber is due to the combination of two sets of the multiple-order resonances of these two layers. Besides, the size changes of the metallic layers have the ability to tune the frequencies of the six-band absorber. Employing the results, we also present a six-band polarization tunable absorber through varying the sizes of the structure in two orthogonal polarization directions. Moreover, nine-band terahertz absorber can be achieved by using a three-layer stacked structure. Simulation results indicate that the absorber possesses nine distinct resonance bands, and average absorptivities of them are larger than 94.03%. The six-band or nine-band absorbers obtained here have potential applications in many optoelectronic and engineering technology areas.

  10. Combined parasitological and molecular-based diagnostic tools improve the detection of Trypanosoma cruzi in single peripheral blood samples from patients with Chagas disease

    Directory of Open Access Journals (Sweden)

    Fabiana Caroline Zempulski Volpato

    Full Text Available Abstract INTRODUCTION In order to detect Trypanosoma cruzi and determine the genetic profiles of the parasite during the chronic phase of Chagas disease (ChD, parasitological and molecular diagnostic methods were used to assess the blood of 91 patients without specific prior treatment. METHODS Blood samples were collected from 68 patients with cardiac ChD and 23 patients with an indeterminate form of ChD, followed by evaluation using blood culture and polymerase chain reaction. T . cruzi isolates were genotyped using three different genetic markers. RESULTS: Blood culture was positive in 54.9% of all patients, among which 60.3% had the cardiac form of ChD, and 39.1% the indeterminate form of ChD. There were no significant differences in blood culture positivity among patients with cardiac and indeterminate forms. Additionally, patient age and clinical forms did not influence blood culture results. Polymerase chain reaction (PCR was positive in 98.9% of patients, although comparisons between blood culture and PCR results showed that the two techniques did not agree. Forty-two T . cruzi stocks were isolated, and TcII was detected in 95.2% of isolates. Additionally, one isolate corresponded to TcIII or TcIV, and another corresponded to TcV or TcVI. CONCLUSIONS Blood culture and PCR were both effective for identifying T. cruzi using a single blood sample, and their association did not improve parasite detection. However, we were not able to establish an association between the clinical form of ChD and the genetic profile of the parasite.

  11. 12 Weeks of Combined Endurance and Resistance Training Reduces Innate Markers of Inflammation in a Randomized Controlled Clinical Trial in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalie Deckx

    2016-01-01

    Full Text Available Previously, we reported that patients with multiple sclerosis (MS demonstrate improved muscle strength, exercise tolerance, and lean tissue mass following a combined endurance and resistance exercise program. However, the effect of exercise on the underlying disease pathogenesis remains elusive. Since recent evidence supports a crucial role of dendritic cells (DC in the pathogenesis of MS, we investigated the effect of a 12-week combined exercise program in MS patients on the number and function of DC. We demonstrate an increased number of plasmacytoid DC (pDC following the exercise program. These pDC display an activated phenotype, as evidenced by increased numbers of circulating CD62L+ and CD80+ pDC. Interestingly, the number of CD80+ pDC positively correlates with the presence of IL-10-producing regulatory type 1 cells (Tr1, an important cell type for maintaining peripheral tolerance to self-antigens. In addition, decreased production of the inflammatory mediators, TNF-α and MMP-9, upon Toll-like receptor (TLR stimulation was found at the end of the exercise program. Overall, our findings suggest that the 12-week exercise program reduces the secretion of inflammatory mediators upon TLR stimulation and promotes the immunoregulatory function of circulating pDC, suggestive for a favorable impact of exercise on the underlying immunopathogenesis of MS.

  12. Diagnostic performance of combined noninvasive anatomic and functional assessment with dual-source CT and adenosine-induced stress dual-energy CT for detection of significant coronary stenosis.

    Science.gov (United States)

    Ko, Sung Min; Choi, Jin Woo; Hwang, Hweung Kon; Song, Meong Gun; Shin, Je Kyoun; Chee, Hyun Keun

    2012-03-01

    The purpose of our study was to prospectively evaluate the incremental diagnostic value of combined dual-source coronary CT angiography (CTA) and CT myocardial perfusion imaging (MPI) for the detection of significant coronary stenoses. Forty-five patients with known coronary artery disease detected by dual-source coronary CTA were investigated by adenosine-induced stress dual-source CTA and conventional coronary angiography. Analysis was performed in three steps: classification of coronary stenosis severity using dual-source coronary CTA, identification of myocardial perfusion defects using rest and stress CT MPI, and reclassification of coronary stenosis severity according to combined dual-source coronary CTA and CT MPI. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of dual-source coronary CTA before and after CT MPI were calculated on a per-vessel basis compared with conventional coronary angiography as the standard of reference. Dual-source coronary CTA revealed 87 significantly stenotic vessels in 45 patients. Conventional coronary angiography revealed significant stenoses in 73 vessels in 42 patients. CT MPI showed myocardial perfusion defects in 81 vessel territories in 43 patients. After the CT MPI analysis, dual-source coronary CTA identified significant stenoses in 77 coronary vessels in 42 patients. Sensitivity, specificity, PPV, and NPV of the dual-source coronary CTA on a per-vessel basis before CT MPI were 91.8%, 67.7%, 73.6%, and 87.5%, respectively, and after CT MPI were 93.2%, 85.5%, 88.3%, and 91.4%, respectively. The area under the receiver operating characteristic curve increased significantly from 0.798 to 0.893 (p = 0.004). Combined dual-source coronary CTA and CT MPI provides incremental diagnostic value compared with dual-source coronary CTA alone for the detection of significant coronary stenoses.

  13. Technical Note: Combination of multiple EPID imager layers improves image quality and tracking performance of low contrast-to-noise objects.

    Science.gov (United States)

    Yip, Stephen S F; Rottmann, Joerg; Chen, Haijian; Morf, Daniel; Füglistaller, Rony; Star-Lack, Josh; Zentai, George; Berbeco, Ross

    2017-09-01

    We hypothesized that combining multiple amorphous silicon flat panel layers increases photon detection efficiency in an electronic portal imaging device (EPID), improving image quality and tracking accuracy of low-contrast targets during radiotherapy. The prototype imager evaluated in this study contained four individually programmable layers each with a copper converter layer, Gd 2 O 2 S scintillator, and active-matrix flat panel imager (AMFPI). The imager was placed on a Varian TrueBeam linac and a Las Vegas phantom programmed with sinusoidal motion (peak-to-peak amplitude = 20 mm, period = 3.5 s) was imaged at a frame rate of 10 Hz with one to four layers activated. Number of visible circles and CNR of least visible circle (depth = 0.5 mm, diameter = 7 mm) was computed to assess the image quality of single and multiple layers. A previously validated tracking algorithm was employed for auto-tracking. Tracking error was defined as the difference between the programmed and tracked positions of the circle. Pearson correlation coefficient (R) of CNR and tracking errors was computed. Motion-induced blurring significantly reduced circle visibility. During four cycles of phantom motion, the number of visible circles varied from 11-23, 13-24, 15-25, and 16-26 for one-, two-, three-, and four-layer imagers, respectively. Compared with using only a single layer, combining two, three, and four layers increased the median CNR by factors of 1.19, 1.42, and 1.71, respectively and reduced the average tracking error from 3.32 mm to 1.67 mm to 1.47 mm, and 0.74 mm, respectively. Significant correlations (P~10 -9 ) were found between the tracking error and CNR. Combination of four conventional EPID layers significantly improves the EPID image quality and tracking accuracy for a poorly visible object which is moving with a frequency and amplitude similar to respiratory motion. © 2017 American Association of Physicists in Medicine.

  14. Optical diagnostics of intermittent flows

    DEFF Research Database (Denmark)

    Okulov, V.L.; Naumov, I.V.; Sørensen, Jens Nørkær

    2007-01-01

    image velocimetry, frequently give erroneous results, especially for the transition flow and developed nonstationary flow. However, their combined use in diagnostics of unsteady (intermittent) flows significantly improves both the temporal and spatial resolution of measurements. Such a complex approach...

  15. Diagnostic hematology of reptiles.

    Science.gov (United States)

    Stacy, Nicole I; Alleman, A Rick; Sayler, Katherine A

    2011-03-01

    The hematologic evaluation of reptiles is an indispensable diagnostic tool in exotic veterinary practice. The diversity of reptile species, their characteristic physiologic features, and effects of intrinsic and extrinsic factors present unique challenges for accurate interpretation of the hemogram. Combining the clinical presentation with hematologic findings provides valuable information in the diagnosis and monitoring of disease and helps guide the clinician toward therapy and further diagnostic testing. This article outlines the normal and pathologic morphology of blood cells of reptile species. The specific comparative aspects of reptiles are emphasized, and structural and functional abnormalities in the reptilian hemogram are described. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Diagnostic Performance of Combined Contrast-Enhanced Magnetic Resonance Angiography and Phase-Contrast Magnetic Resonance Imaging in Suspected Subclavian Steal Syndrome.

    Science.gov (United States)

    Tsao, Teng-Fu; Cheng, Kai-Lun; Shen, Chao-Yu; Wu, Ming-Chi; Huang, Hsin-Hui; Su, Chun-Hung; Chen, Fong-Lin; Tyan, Yeu-Sheng; Lin, Yung-Chang

    2016-05-01

    The study sought to evaluate the efficacy of magnetic resonance imaging (MRI) in patients with suspected subclavian steal syndrome (SSS) using both contrast-enhanced (CE) MR angiography and phase-contrast (PC) MRI. Fifteen suspected SSSs from 13 patients were evaluated using CE-MR angiography and PC-MRI. Ten patients also received dynamic CE-MR angiography. All MRI examinations were technically successful. By combining CE-MR angiography with PC-MRI, 10 SSSs were diagnosed in 9 patients. The delay enhancement dynamic technique predicted SSS with a sensitivity, specificity, and accuracy of 57.1%, 100%, and 72.7%, respectively. Without the dynamic technique, affected delay-enhanced arteries were poorly visualized and could be mistaken for occluded vessels. Retrograde vertebral flow by PC-MRI was used to predict ipsilateral SSS with a sensitivity, specificity, and accuracy of 100%, 60%, and 86.7%, respectively. There were 2 false positives including 1 patient with a proximal total occlusion of the affected vertebral artery and another with brachiocephalic steal syndrome rather than SSS. This suggested that retrograde vertebral flow does not always indicate SSS. CE-MR angiography combined with PC-MRI is efficacious when evaluating SSS in clinical practice. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

  17. The diagnostic value of SE MRI and DWI of the spine in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Dutoit, Julie C.; Vanderkerken, Matthias A.; Dochy, Frederick; Verstraete, Koenraad L. [Ghent University Hospital, Department of Radiology, Ghent (Belgium); Anthonissen, Joris [Ghent University, Ghent (Belgium)

    2014-11-15

    To evaluate DWI of the bone marrow in the differentiation of monoclonal gammopathy of undetermined significance (MGUS), smouldering myeloma (SMM) and multiple myeloma (MM). The retrospective study includes 64 patients with MGUS, 27 with SMM, 64 with new MM and 12 controls. Signal intensity (SI) of spinal SE-MRI and DWI (b0-1000) as well as apparent diffusion coefficients (ADC) were measured in the T10 and L3. Qualitative assessment of b-images was performed by one experienced radiologist. ADC600 and ADC1000 are the best ADC values in differentiating patient groups (p < 0.030). SIT2, SIb1000 and ADC1000 are higher and SIT1 lower in L3 compared to T10 (p < 0.050). All quantitative parameters of L3 can differentiate significantly between MGUS and MM (p < 0.050) and between patients with percentage plasma cells (PC%) between 0-10 % compared to >50 % (p = 0.001). Only SIT2 for L3 can differentiate MGUS from SMM (p = 0.044) and PC%0-10 from PC%10-25 (p = 0.033). Qualitative interpretation of b1000 images allows differentiating MM patients from those with MGUS or SMM (p < 0.001). Spinal SE-MRI can differentiate among MGUS, SMM, MM and control subjects. DWI based on the SI on b1000 images and ADC values is increased in MM compared to MGUS and SMM. Qualitative assessment of b-images can differentiate MM from MGUS or SMM. (orig.)

  18. Roche/BIOTECON Diagnostics LightCycler foodproof L. monocytogenes detection kit in combination with ShortPrep foodproof II Kit. Performance-Tested Method 070401.

    Science.gov (United States)

    Junge, Benjamin; Berghof-Jäger, Kornelia

    2006-01-01

    A method was developed for the detection of L. monocytogenes in food based on real-time polymerase chain reaction (PCR). This advanced PCR method was designed to reduce the time needed to achieve results from PCR reactions and to enable the user to monitor the amplification of the PCR product simultaneously, in real-time. After DNA isolation using the Roche/BIOTECON Diagnostics ShortPrep foodproof II Kit (formerly called Listeria ShortPrep Kit) designed for the rapid preparation of L. monocytogenes DNA for direct use in PCR, the real-time detection of L. monocytogenes DNA is performed by using the Roche/BIOTECON Diagnostics LightCycler foodproof L. monocytogenes Detection Kit. This kit provides primers and hybridization probes for sequence-specific detection, convenient premixed reagents, and different controls for reliable interpretation of results. For repeatability studies, 20 different foods, covering the 15 food groups recommended from the AOAC Research Institute (AOAC RI) for L. monocytogenes detection were analyzed: raw meats, fresh produce/vegetables, processed meats, seafood, egg and egg products, dairy (cultured/noncultured), spices, dry foods, fruit/juices, uncooked pasta, nuts, confectionery, pet food, food dyes and colorings, and miscellaneous. From each food 20, samples were inoculated with a low level (1-10 colony-forming units (CFU)/25 g) and 20 samples with a high level (10-50 CFU/25 g) of L. monocytogenes. Additionally, 5 uninoculated samples were prepared from each food. The food samples were examined with the test kits and in correlation with the cultural methods according to U.S. Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) or U.S. Department of Agriculture (USDA)/Food Safety and Inspection Service (FSIS) Microbiology Laboratory Guidebook. After 48 h of incubation, the PCR method in all cases showed equal or better results than the reference cultural FDA/BAM or USDA/FSIS methods. Fifteen out of 20 tested food types

  19. Revisiting Tversky's diagnosticity principle.

    Science.gov (United States)

    Evers, Ellen R K; Lakens, Daniël

    2014-01-01

    Similarity is a fundamental concept in cognition. In 1977, Amos Tversky published a highly influential feature-based model of how people judge the similarity between objects. The model highlights the context-dependence of similarity judgments, and challenged geometric models of similarity. One of the context-dependent effects Tversky describes is the diagnosticity principle. The diagnosticity principle determines which features are used to cluster multiple objects into subgroups. Perceived similarity between items within clusters is expected to increase, while similarity between items in different clusters decreases. Here, we present two pre-registered replications of the studies on the diagnosticity effect reported in Tversky (1977). Additionally, one alternative mechanism that has been proposed to play a role in the original studies, an increase in the choice for distractor items (a substitution effect, see Medin et al., 1995), is examined. Our results replicate those found by Tversky (1977), revealing an average diagnosticity-effect of 4.75%. However, when we eliminate the possibility of substitution effects confounding the results, a meta-analysis of the data provides no indication of any remaining effect of diagnosticity.

  20. The diagnostic accuracy of dual-view digital mammography, single-view breast tomosynthesis and a dual-view combination of breast tomosynthesis and digital mammography in a free-response observer performance study.

    Science.gov (United States)

    Svahn, T; Andersson, I; Chakraborty, D; Svensson, S; Ikeda, D; Förnvik, D; Mattsson, S; Tingberg, A; Zackrisson, S

    2010-01-01

    The purpose of the present study was to compare the diagnostic accuracy of dual-view digital mammography (DM), single-view breast tomosynthesis (BT) and BT combined with the opposite DM view. Patients with subtle lesions were selected to undergo BT examinations. Two radiologists who are non-participants in the study and have experience in using DM and BT determined the locations and extents of lesions in the images. Five expert mammographers interpreted the cases using the free-response paradigm. The task was to mark and rate clinically reportable findings suspicious for malignancy and clinically relevant benign findings. The marks were scored with reference to the outlined regions into lesion localization or non-lesion localization, and analysed by the jackknife alternative free-response receiver operating characteristic method. The analysis yielded statistically significant differences between the combined modality and dual-view DM (p < 0.05). No differences were found between single-view BT and dual-view DM or between single-view BT and the combined modality.

  1. Metabolite identification of triptolide by data-dependent accurate mass spectrometric analysis in combination with online hydrogen/deuterium exchange and multiple data-mining techniques.

    Science.gov (United States)

    Du, Fuying; Liu, Ting; Liu, Tian; Wang, Yongwei; Wan, Yakun; Xing, Jie

    2011-10-30

    Triptolide (TP), the primary active component of the herbal medicine Tripterygium wilfordii Hook F, has shown promising antileukemic and anti-inflammatory activity. The pharmacokinetic profile of TP indicates an extensive metabolic elimination in vivo; however, its metabolic data is rarely available partly because of the difficulty in identifying it due to the absence of appropriate ultraviolet chromophores in the structure and the presence of endogenous interferences in biological samples. In the present study, the biotransformation of TP was investigated by improved data-dependent accurate mass spectrometric analysis, using an LTQ/Orbitrap hybrid mass spectrometer in conjunction with the online hydrogen (H)/deuterium (D) exchange technique for rapid structural characterization. Accurate full-scan MS and MS/MS data were processed with multiple post-acquisition data-mining techniques, which were complementary and effective in detecting both common and uncommon metabolites from biological matrices. As a result, 38 phase I, 9 phase II and 8 N-acetylcysteine (NAC) metabolites of TP were found in rat urine. Accurate MS/MS data were used to support assignments of metabolite structures, and online H/D exchange experiments provided additional evidence for exchangeable hydrogen atoms in the structure. The results showed the main phase I metabolic pathways of TP are hydroxylation, hydrolysis and desaturation, and the resulting metabolites subsequently undergo phase II processes. The presence of NAC conjugates indicated the capability of TP to form reactive intermediate species. This study also demonstrated the effectiveness of LC/HR-MS(n) in combination with multiple post-acquisition data-mining methods and the online H/D exchange technique for the rapid identification of drug metabolites. Copyright © 2011 John Wiley & Sons, Ltd.

  2. Companion diagnostics

    DEFF Research Database (Denmark)

    Jørgensen, Jan Trøst; Hersom, Maria

    2016-01-01

    . Despite having discussed personalized medicine for more than a decade, we still see that most drug prescriptions for severe chronic diseases are largely based on 'trial and error' and not on solid biomarker data. However, with the advance of molecular diagnostics and a subsequent increased understanding...

  3. Lab-on-a-chip enabled HLA diagnostic: combined sample preparation and real time PCR for HLA-B57 diagnosis

    Science.gov (United States)

    Gärtner, Claudia; Becker, Holger; Hlawatsch, Nadine; Klemm, Richard; Moche, Christian; Schattschneider, Sebastian; Frank, Rainer; Willems, Andreas

    2015-05-01

    The diverse human HLA (human leukocyte antigen) system is responsible for antigen presentation and recognition. It is essential for the immune system to maintain a stable defense line, but also is also involved in autoimmunity as well as metabolic disease. HLA-haplotype (HLA-B27), for instance, is associated with inflammatory diseases such as Bechterew's disease. The administration of the HIV drug Abacavir in combination with another HLA-haplotype (HLAB57) is associated with severe hypersensitivity reactions. Accordingly, the HLA status has to be monitored for diagnosis or prior to start of therapy. Along this line, a miniaturized microfluidic platform has been developed allowing performing the complete analytical process from "sample-in" to "answer-out" in a point-of-care environment. The main steps of the analytical cascade inside the integrated system are blood cell lysis and DNA isolation, DNA purification, real-time PCR and quantitative monitoring of the rise of a fluorescent signal appearing during the PCR based sequence amplification. All bio-analytical steps were intended to be performed inside one chip and will be actuated, controlled and monitored by a matching device. This report will show that all required processes are established and tested and all device components work well and interact with the functional modules on the chips in a harmonized fashion.

  4. Systematic review with meta-analysis: diagnostic performance of the combination of pepsinogen, gastrin-17 and anti-Helicobacter pylori antibodies serum assays for the diagnosis of atrophic gastritis.

    Science.gov (United States)

    Zagari, R M; Rabitti, S; Greenwood, D C; Eusebi, L H; Vestito, A; Bazzoli, F

    2017-10-01

    The combination of pepsinogen, gastrin-17 and anti-H. pylori antibodies serological assays (panel test) is a non-invasive tool for the diagnosis of atrophic gastritis. However, the diagnostic reliability of this test is still uncertain. To assess the diagnostic performance of the serum panel test for the diagnosis of atrophic gastritis. Medline via PubMed, Embase, Scopus, Cochrane Library databases and abstracts of international conferences proceedings were searched from January 1995 to December 2016 using the primary keywords "pepsinogens," "gastrin," "atrophic gastritis," "gastric precancerous lesions." Studies were included if they assessed the accuracy of the serum panel test for the diagnosis of atrophic gastritis using histology according to the updated Sydney System as reference standard. Twenty studies with a total of 4241 subjects assessed the performance of serum panel test for the diagnosis of atrophic gastritis regardless of the site in the stomach. The summary sensitivity was 74.7% (95% confidence interval (CI), 62.0-84.3) and the specificity was 95.6% (95%CI, 92.6-97.4). With a prevalence of atrophic gastritis of 27% (median prevalence across the studies), the negative predictive value was 91%. Few studies with small sample size assessed the performance of the test in detecting the site of atrophic gastritis. The combination of pepsinogen, gastrin-17 and anti-H. pylori antibodies serological assays appears to be a reliable tool for the diagnosis of atrophic gastritis. This test may be used for screening subjects or populations at high risk of gastric cancer for atrophic gastritis; however, a cost-effectiveness analysis is needed. © 2017 John Wiley & Sons Ltd.

  5. Internal correction of spectral interferences and mass bias for selenium metabolism studies using enriched stable isotopes in combination with multiple linear regression.

    Science.gov (United States)

    Lunøe, Kristoffer; Martínez-Sierra, Justo Giner; Gammelgaard, Bente; Alonso, J Ignacio García

    2012-03-01

    The analytical methodology for the in vivo study of selenium metabolism using two enriched selenium isotopes has been modified, allowing for the internal correction of spectral interferences and mass bias both for total selenium and speciation analysis. The method is based on the combination of an already described dual-isotope procedure with a new data treatment strategy based on multiple linear regression. A metabolic enriched isotope ((77)Se) is given orally to the test subject and a second isotope ((74)Se) is employed for quantification. In our approach, all possible polyatomic interferences occurring in the measurement of the isotope composition of selenium by collision cell quadrupole ICP-MS are taken into account and their relative contribution calculated by multiple linear regression after minimisation of the residuals. As a result, all spectral interferences and mass bias are corrected internally allowing the fast and independent quantification of natural abundance selenium ((nat)Se) and enriched (77)Se. In this sense, the calculation of the tracer/tracee ratio in each sample is straightforward. The method has been applied to study the time-related tissue incorporation of (77)Se in male Wistar rats while maintaining the (nat)Se steady-state conditions. Additionally, metabolically relevant information such as selenoprotein synthesis and selenium elimination in urine could be studied using the proposed methodology. In this case, serum proteins were separated by affinity chromatography while reverse phase was employed for urine metabolites. In both cases, (74)Se was used as a post-column isotope dilution spike. The application of multiple linear regression to the whole chromatogram allowed us to calculate the contribution of bromine hydride, selenium hydride, argon polyatomics and mass bias on the observed selenium isotope patterns. By minimising the square sum of residuals for the whole chromatogram, internal correction of spectral interferences and mass

  6. Cost-effectiveness of invitation to food supplementation early in pregnancy combined with multiple micronutrients on infant survival: analysis of data from MINIMat randomized trial, Bangladesh.

    Science.gov (United States)

    Shaheen, Rubina; Persson, Lars Åke; Ahmed, Shakil; Streatfield, Peter Kim; Lindholm, Lars

    2015-05-28

    Absence of cost-effectiveness (CE) analyses limits the relevance of large-scale nutrition interventions in low-income countries. We analyzed if the effect of invitation to food supplementation early in pregnancy combined with multiple micronutrient supplements (MMS) on infant survival represented value for money compared to invitation to food supplementation at usual time in pregnancy combined with iron-folic acid. Outcome data, infant mortality (IM) rates, came from MINIMat trial (Maternal and Infant Nutrition Interventions, Matlab, ISRCTN16581394). In MINIMat, women were randomized to early (E around 9 weeks of pregnancy) or usual invitation (U around 20 weeks) to food supplementation and daily doses of 30 mg, or 60 mg iron with 400 μgm of folic acid, or MMS with 15 micronutrients including 30 mg iron and 400 μgm of folic acid. In MINIMat, EMMS significantly reduced IM compared to UFe60F (U plus 60 mg iron 400 μgm Folic acid). We present incremental CE ratios for incrementing UFe60F to EMMS. Costing data came mainly from a published study. By incrementing UFe60F to EMMS, one extra IM could be averted at a cost of US$907 and US$797 for NGO run and government run CNCs, respectively, and at US$1024 for a hypothetical scenario of highest cost. These comparisons generated one extra life year (LY) saved at US$30, US$27, and US$34, respectively. Incrementing UFe60F to EMMS in pregnancy seems worthwhile from health economic and public health standpoints. Maternal and Infant Nutrition Interventions, Matlab; ISRCTN16581394 ; Date of registration: Feb 16, 2009.

  7. Left ventricular hypertrophy index based on a combination of frontal and transverse planes in the ECG and VCG: Diagnostic utility of cardiac vectors

    Science.gov (United States)

    Bonomini, Maria Paula; Juan Ingallina, Fernando; Barone, Valeria; Antonucci, Ricardo; Valentinuzzi, Max; Arini, Pedro David

    2016-04-01

    The changes that left ventricular hypertrophy (LVH) induces in depolarization and repolarization vectors are well known. We analyzed the performance of the electrocardiographic and vectorcardiographic transverse planes (TP in the ECG and XZ in the VCG) and frontal planes (FP in the ECG and XY in the VCG) to discriminate LVH patients from control subjects. In an age-balanced set of 58 patients, the directions and amplitudes of QRS-complexes and T-wave vectors were studied. The repolarization vector significantly decreased in modulus from controls to LVH in the transverse plane (TP: 0.45±0.17mV vs. 0.24±0.13mV, p<0.0005 XZ: 0.43±0.16mV vs. 0.26±0.11mV, p<0.005) while the depolarization vector significantly changed in angle in the electrocardiographic frontal plane (Controls vs. LVH, FP: 48.24±33.66° vs. 46.84±35.44°, p<0.005, XY: 20.28±35.20° vs. 19.35±12.31°, NS). Several LVH indexes were proposed combining such information in both ECG and VCG spaces. A subset of all those indexes with AUC values greater than 0.7 was further studied. This subset comprised four indexes, with three of them belonging to the ECG space. Two out of the four indexes presented the best ROC curves (AUC values: 0.78 and 0.75, respectively). One index belonged to the ECG space and the other one to the VCG space. Both indexes showed a sensitivity of 86% and a specificity of 70%. In conclusion, the proposed indexes can favorably complement LVH diagnosis

  8. [Preliminary applicability evaluation of Prostate Imaging Reporting and Data System version 2 diagnostic score in 3.0T multi-parameters magnetic resonance imaging combined with prostate specific antigen density for prostate cancer].

    Science.gov (United States)

    Zuo, M Z; Zhao, W L; Wei, C G; Zhang, C Y; Wen, R; Gu, Y F; Li, M J; Zhang, Y Y; Wu, J F; Li, X; Shen, J K

    2017-12-19

    Objective: To investigate the preliminary applicability of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score in the condition of 3.0T multi-parametric magnetic resonance imaging (Mp-MRI) combined with clinical classic indicators for the diagnosis of prostate cancer (PCa). Methods: The clinical and MRI materials of 247 patients of suspicious prostate disease treated in Second Affiliated Hospital of Soochow University from June 2015 to November 2016 were analyzed retrospectively, including 110 cases with PCa and 137 cases without cancer.All cases underwent the high-resolution axial T(2)-weighted imaging (T(2)WI), diffusion weighted imaging (DWI) and dynamic contrast enhancement-magnetic resonance imaging (DCE-MRI) and were confirmed pathologically by puncture biopsies.The Mp-MRI materials of all cases were scored according to PI-RADS v2.The prostate volume and prostate specific antigen (PSA) density (PSAD) value were calculated according to the formulas.The univariate and multivariate analysis were performed for the observed indicators (age, prostate volume, PSA, PSAD and PI-RADS v2 score) to determine the independent predictors for PCa.Then, a Logistic regression model (combined prediction model) was established by the independent predictors for combined diagnosis of PCa.The receiver operating characteristic curve (ROC) curve analysis was performed to get the sensitivity and specificity of each independent predictor and the model to diagnose PCa.The differences of AUC values of each independent predictor and the model were compared with each other to evaluate the diagnostic performance for PCa. Results: The differences in the age, prostate volume, PSA, PSAD and the PI-RADS v2 score between patients with PCa and non-cancer group were all statistically significant ( t =2.870, Z =-4.230, -7.787, -9.477, -10.826, all P PI-RADS v2 score were independent predictors for PCa ( OR =3.331, 10.546, both P PI-RADS v2 score and PSAD to forecast PCa was

  9. Discovery of small molecules binding to the normal conformation of prion by combining virtual screening and multiple biological activity evaluation methods

    Science.gov (United States)

    Li, Lanlan; Wei, Wei; Jia, Wen-Juan; Zhu, Yongchang; Zhang, Yan; Chen, Jiang-Huai; Tian, Jiaqi; Liu, Huanxiang; He, Yong-Xing; Yao, Xiaojun

    2017-12-01

    Conformational conversion of the normal cellular prion protein, PrPC, into the misfolded isoform, PrPSc, is considered to be a central event in the development of fatal neurodegenerative diseases. Stabilization of prion protein at the normal cellular form (PrPC) with small molecules is a rational and efficient strategy for treatment of prion related diseases. However, few compounds have been identified as potent prion inhibitors by binding to the normal conformation of prion. In this work, to rational screening of inhibitors capable of stabilizing cellular form of prion protein, multiple approaches combining docking-based virtual screening, steady-state fluorescence quenching, surface plasmon resonance and thioflavin T fluorescence assay were used to discover new compounds interrupting PrPC to PrPSc conversion. Compound 3253-0207 that can bind to PrPC with micromolar affinity and inhibit prion fibrillation was identified from small molecule databases. Molecular dynamics simulation indicated that compound 3253-0207 can bind to the hotspot residues in the binding pocket composed by β1, β2 and α2, which are significant structure moieties in conversion from PrPC to PrPSc.

  10. 3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

    Science.gov (United States)

    Cui, P. X.; Lian, F. L.; Wang, Y.; Wen, Yi; Chu, W. S.; Zhao, H. F.; Zhang, S.; Li, J.; Lin, D. H.; Wu, Z. Y.

    2014-02-01

    Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrPC) to the post-translationally modified form (PrPSc) is thought to be relevant to Cu2+ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrPC) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases.

  11. Sensitive determination of neurotransmitters in urine by microchip electrophoresis with multiple-concentration approaches combining field-amplified and reversed-field stacking.

    Science.gov (United States)

    Zhang, Yan; Zhang, Yi; Wang, Guan; Chen, Wujuan; Li, Yi; Zhang, Yating; He, Pingang; Wang, Qingjiang

    2016-07-01

    Microchip electrophoresis (MCE) is particularly attractive as it provides high sensitivity and selectivity, short analysis time and low sample consumption. An on-line preconcentration strategy combining field-amplified stacking (FASS) and reversed-field stacking (RFS) was developed for efficient and sensitive analysis of neurotransmitters in real urine samples by MCE with laser induced fluorescence (LIF) detection. In this study, the multiple-preconcentration strategy greatly improves the sensitivity enhancement and surpass other conventional analytical methods for neurotransmitters detection. Under optimal conditions, the separation of three neurotransmitters (dopamine, norepinephrine and serotonin), was achieved within 3min with limits of detection (S/N=3) of 1.69, 2.35, and 2.73nM, respectively. The detection sensitivities were improved by 201-, 182-, and 292-fold enhancement, for the three neurotransmitters respectively. Other evaluation parameters such as linear correlation coefficients were considered as satisfactory. A real urine sample was analyzed with recoveries of 101.8-106.4%. The proposed FASS-RFS-MCE method was characterized in terms of precision, linearity, accuracy and successfully applied for rapid and sensitive determination of three neurotransmitters in human urine. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. A Phase I/II Trial of DCVac/IR Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Young-Min; Lee, Hyung-Sik; Kwon, Hyuk-Chan; Han, Sang-Young; Choi, Jong-Cheol [Donga Univ. School of Medicine, Busan (Korea, Republic of); Chung, Ju-Seop; Kim, Chang-Won; Kim, Dong-Won; Kang, Chi-Duk [Busan National University College of Medicine, Busan (Korea, Republic of)

    2008-06-15

    To assess the toxicity and tumor response induced by DCVac/IR dendritic cell (DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of 6x10{sup 6} DCs were packed into a vial (DCVac/IR, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses (3x10{sup 6} to 12x10{sup 6} DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Of the 24 registered patients, 22 received the DCs

  13. Diagnostic performance of coronary CT angiography, stress dual-energy CT perfusion, and stress perfusion single-photon emission computed tomography for coronary artery disease: Comparison with combined invasive coronary angiography and stress perfusion cardiac MRI

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hyun Woo; Ko, Sung Min; Hwang, Hweung Kon; So, Young; Yi, Jeong Geun [Konkuk University Medical Center, Research Institute of Biomedical Science, Konkuk University School of Medicine, Seoul (Korea, Republic of); Lee, Eun Jeong [Dept. of Nuclear Medicine, Seoul Medical Center, Seoul (Korea, Republic of)

    2017-06-15

    To investigate the diagnostic performance of coronary computed tomography angiography (CCTA), stress dual-energy computed tomography perfusion (DE-CTP), stress perfusion single-photon emission computed tomography (SPECT), and the combinations of CCTA with myocardial perfusion imaging (CCTA + DE-CTP and CCTA + SPECT) for identifying coronary artery stenosis that causes myocardial hypoperfusion. Combined invasive coronary angiography (ICA) and stress perfusion cardiac magnetic resonance (SP-CMR) imaging are used as the reference standard. We retrospectively reviewed the records of 25 patients with suspected coronary artery disease, who underwent CCTA, DE-CTP, SPECT, SP-CMR, and ICA. The reference standard was defined as ≥ 50% stenosis by ICA, with a corresponding myocardial hypoperfusion on SP-CMR. For per-vascular territory analysis, the sensitivities of CCTA, DE-CTP, SPECT, CCTA + DE-CTP, and CCTA + SPECT were 96, 96, 68, 93, and 68%, respectively, and specificities were 72, 75, 89, 85, and 94%, respectively. The areas under the receiver operating characteristic curve (AUCs) were 0.84 ± 0.05, 0.85 ± 0.05, 0.79 ± 0.06, 0.89 ± 0.04, and 0.81 ± 0.06, respectively. For per-patient analysis, the sensitivities of CCTA, DE-CTP, SPECT, CCTA + DE-CTP, and CCTA + SPECT were 100, 100, 89, 100, and 83%, respectively; the specificities were 14, 43, 57, 43, and 57%, respectively; and the AUCs were 0.57 ± 0.13, 0.71 ± 0.11, 0.73 ± 0.11, 0.71 ± 0.11, and 0.70 ± 0.11, respectively. The combination of CCTA and DE-CTP enhances specificity without a loss of sensitivity for detecting hemodynamically significant coronary artery stenosis, as defined by combined ICA and SP-CMR.

  14. THE RELIABILITY OF IDENTIFICATION EVIDENCE WITH MULTIPLE LINEUPS

    Directory of Open Access Journals (Sweden)

    Nick J. Broers

    2013-01-01

    Full Text Available This study aimed to establish the diagnostic value of multiple lineup decisions made for portrait, body, and profile lineups, including multiple target/suspect choices, rejections, foil choices, and don’t know answers. A total of 192 participants identified a thief and a victim of theft from independent simultaneous target-present or target-absent 6-person portrait, body and profile lineups after watching one of two stimulus films. As hypothesized, multiple target/suspect choices had incriminating value whereas multiple rejections, foil choices, and don’t know answers had mostly exonerating value. For suspect choices, the combination of all three lineup modes consistently elicited high diagnosticities across targets. Combinations of non-suspect choices (rejections, foil choices, or don’t know answers were less successful and the different combinations showed less consistency in terms of diagnosticity. It was concluded that the use of multiple lineups, such as different facial poses and different aspects of a person should be particularly beneficial in three situations: if a witness only saw the perpetrator from a pose different than the frontal view normally used for lineups; if one or more witnesses saw the perpetrator from more than one perspective; and if different witnesses saw the perpetrator from different perspectives.

  15. Comparative diagnostic performance of {sup 18}F-FDG PET/CT versus whole-body MRI for determination of remission status in multiple myeloma after stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten; Peldschus, Kersten; Bannas, Peter; Herrmann, Jochen; Habermann, Christian R.; Adam, Gerhard; Weber, Christoph [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Muenster, Silvia [University Medical Center Hamburg-Eppendorf, Department of Nuclear Medicine, Hamburg (Germany); Stuebig, Thomas; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg (Germany)

    2013-02-15

    To compare the diagnostic performance of whole-body magnetic resonance imaging (WBMRI) versus {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) for determination of remission status in patients with multiple myeloma (MM) after stem cell transplantation (SCT). Thirty-one patients were examined by both WBMRI and PET/CT after SCT. Imaging results and clinical remission status as determined by the clinical gold standard (Uniform Response Criteria) were compared. One hundred four lesions were detected in 21 patients. PET/CT had a sensitivity of 50.0 %, a specificity of 85.7 %, a positive predictive value of 62.5 %, a negative predictive value of 78.3 %, and an overall accuracy of 74.2 % for determination of remission status. MRI had a sensitivity of 80.0 %, a specificity of 38.1 %, a positive predictive value of 38.1 %, a negative predictive value of 80 %, and an overall accuracy of 51.6 %. Concordant results were observed in only 12 (11.5 %) of the 104 lesions. In the post-treatment setting, both FDG PET/CT and WBMRI provide information about the extent of disease, allowing for a more comprehensive evaluation of persisting or recurrent myeloma. MRI may often be false positive because of persistent non-viable lesions. Therefore, PET/CT might be more suitable than MRI for determination of remission status. (orig.)

  16. The feasibility and diagnostic accuracy by multiple cardiac biomarkers in emergency chest pain patients: a clinical analysis to compare 290 suspected acute coronary syndrome cases stratified by age and gender in Taiwan.

    Science.gov (United States)

    Hung, Chung-Lieh; Chien, Ding-Kuo; Shih, Shou-Chuan; Chang, Wen-Han

    2016-10-07

    Accurate diagnosis of acute coronary syndrome (ACS) in a timely fashion is challenging in the elderly population, especially elderly women, who usually exhibit atypical clinical symptoms. A multiple cardiac biomarker (MCB) based approach has been shown to improve diagnostic efficacy of ACS. However, data in various age groups and sex differences remain largely unexplored. Point-of-care testing (POCT) was performed on 290 patients (aged ≥18 years) who were admitted to the emergency department (ED) with symptoms of acute chest pain under suspicion of acute coronary syndrome (ACS). The MCB approach in current work assessed four cardiac biomarkers: myoglobin, troponin I, creatine kinase-myocardial band isoenzyme fraction (CK-MB), and brain natriuretic peptide (BNP). Overall, the MCB approach demonstrated considerably higher sensitivity for elderly patients than for younger patients in identifying ACS (80.0 % [64.1-90.0] vs. 52.6 % [37.3-67.5] for ≥65 years and chest pain was 87.5 % [95 % CI: 64-96.5]). In general, the sensitivity of this approach was higher for female patients than for male patients (80 % [58.4-91.9] vs. 61 % [47.8-73.0]). The MCB approach can provide a quick and accurate clinical diagnosis in elderly and female patients, both of whom have traditionally proven to be challenging to diagnose from suspected acute coronary syndrome.

  17. MO-DE-BRA-05: EUTEMPE-RX: Combining E-Learning and Face-To-Face Training to Build Expert Knowledge, Skills and Competences for Medical Physicists in Diagnostic and Interventional Radiology

    Energy Technology Data Exchange (ETDEWEB)

    Bosmans, H [University Hospitals Leuven, Leuven (Belgium); Van Peteghem, N; Creten, S [KU Leuven, Leuven, Vlaams Brabant (Belgium); Mackenzie, A [Royal Surrey County Hospital, Guildford, Surrey (United Kingdom); Vano, E [San Carlos University Hospital, Madrid (Spain); Borowski, M [Klinikum Braunschweig, Braunschweig (Germany); Christofides, S [Nicosia General Hospital, Nicosia (Cyprus); Caruana, C [University of Malta, Msida (Malta)

    2016-06-15

    Purpose: In 2013, the EURATOM authorities of the European Commission decided to support the Horizon2020 project submission ‘EUTEMPE-RX’ that aimed for a new set of course modules to train medical physicists in diagnostic and interventional radiology to expert level with small group deep learning. Each module would consist of 2 phases: an e-learning and a face-to-face phase, each phase requiring typically 40h of participant time. Methods: The European Federation (EFOMP) and 13 European partners, all of them selected for their excellent scientific and/or educational skills, led the 12 course modules. A quality manual ensured the quality of course content and organization. Educational workshops familiarized the teachers with e-learning techniques and methods for assessment. Content was set in accordance with the EC document RP174 that lists learning outcomes in terms of knowledge, skills and competences (KSCs) for different specialties and levels of medical physics. Surveys for stake holder satisfaction were prepared. Results: Today the course modules are being realized. The modules cover most of the KSCs in RP174 document. Teachers have challenged the participants with unique tasks: case studies in medical physics leadership, Monte Carlo simulation of a complete x-ray imaging chain, development of a task specific QA protocol, compilation of optimization plans, simulation tasks with anthropomorphic breast models, etc. Participants undertook practical sessions in modern hospitals and visited a synchrotron facility, a calibration lab, screening organizations, etc. Feedback form quality surveys was very positive and constructive. A sustainability plan has been worked out. Conclusion: The modules have enabled the participants to develop their KSCs and cope with challenges in medical physics. The sustainability plan will be implemented to continue the unique combined e-learning and face to face training at high level training in diagnostic and interventional radiology

  18. Pharmacokinetics of niacin, simvastatin and their metabolites in healthy Chinese subjects after single and multiple doses of a fixed dose combination tablet of niacin extended release/simvastatin.

    Science.gov (United States)

    Liu, M; Wang, X L; Zhang, D; Yang, M; Han, J; Zhang, Y N; Wang, Z L; Liu, H C

    2014-06-01

    A fixed dose combination tablet of niacin extended release (ER)/simvastatin was recently developed in China. This study was designed to assess and compare the pharmacokinetics of niacin, simvastatin and their metabolites in healthy Chinese subjects after single and multiple doses administration. From day 1 to day 7, 12 Chinese subjects were given a tablet every day at approximately 10 p.m. Serial blood samples were collected. Niacin and nicotinuric acid (NUA) in plasma, niacin, NUA, N-methylnicotinamide (MNA) and N-methyl-2-pyridone-5-carboxamide (2PY) in urine, simvastatin and simvastatin acid in plasma were determined by LC/MS/MS methods. Pharmacokinetic parameters on days 1 and 7 were compared. The main pharmacokinetic parameters for the single and multiple doses were as -follows: Niacin: Tmax were 3.8±1.5 h and 3.9±2.0 h; Cmax were 2 091±1 315 ng/ml and 2 323±1 542 ng/ml; AUC0-t were 4 123.88±3 138.48 ng ∙ h/ml and 4 385.98±3 127.05 ng ∙ h/ml. NUA: Tmax were 4.7±1.7 h and 3.8±1.5 h; Cmax were 1 057±549 ng/ml and 1 087±470 ng/ml; AUC0-t were 4 012.49±2 168.68 ng ∙ h/ml and 4 040.45±1 886.57 ng ∙ h/ml. Simvastatin: Tmax were 1.8±1.0 h and 2.5±2.5 h; Cmax were 3.15±1.67 ng/ml and 4.87±4.11 ng/ml; AUC0-t were 9.03±5.10 ng ∙ h/ml and 17.63±13.93 ng ∙ h/ml. Simvastatin acid: Tmax were 5.8±1.7 h and 6.5±1.4 h; Cmax were 4.22±2.10 ng/ml and 9.30±8.09 ng/ml; AUC0-t were 34.65±16.89 ng ∙ h/ml and 61.62±46.41 ng ∙ h/ml. Urine Recovery rate of total niacin: (40.55±7.38)% and (62.87±12.04)%. Compared with those after a single dose, pharmacokinetics of niacin and NUA was similar; total urine recovery of niacin was higher; exposure to simvastatin and simvastatin acid were higher following multiple doses. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Sensory neuronopathy involves the spinal cord and brachial plexus: a quantitative study employing multiple-echo data image combination (MEDIC) and turbo inversion recovery magnitude (TIRM)

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Yi-Fang; Tang, Wei-Jun; Li, Yu-Xin; Geng, Dao-Ying [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Zhu, Dong-Qing; Chen, Xiang-Jun [Fudan University, Department of Neurology, Huashan Hospital, Shanghai (China); Zee, Chi-Shing [University of Southern California Keck School of Medicine, Department of Radiology, Los Angeles, CA (United States)

    2013-01-15

    Sensory neuronopathy (SNN) is a distinctive subtype of peripheral neuropathies, specifically targeting dorsal root ganglion (DRG). We utilized MRI to demonstrate the imaging characteristics of DRG, spinal cord (SC), and brachial plexus at C7 level in SNN. We attempted multiple-echo data image combination (MEDIC) and turbo inversion recovery magnitude (TIRM) methods in nine patients with sensory neuronopathy and compared with those in 16 disease controls and 20 healthy volunteers. All participants underwent MRI for the measurement of DRG, posterior column (PC), lateral column, and spinal cord area (SCA) at C7 level. DRG diameters were obtained through its largest cross section, standardized by dividing sagittal diameter of mid-C7 vertebral canal. We also made comparisons of standardized anteroposterior diameter (APD) and left-right diameters of SC and PC in these groups. Signal intensity and diameter of C7 spinal nerve were assessed on TIRM. Compared to control groups, signal intensities of DRG and PC were higher in SNN patients when using MEDIC, but the standardized diameters were shorter in either DRG or PC. Abnormal PC signal intensities were identified in eight out of nine SNN patients (89 %) with MEDIC and five out of nine (56 %) with T2-weighted images. SCA, assessed with MEDIC, was smaller in SNN patients than in the other groups, with significant reduction of its standardized APD. C7 nerve root diameters, assessed with TIRM, were decreased in SNN patients. MEDIC and TIRM sequences demonstrate increased signal intensities and decreased area of DRG and PC, and decreased diameter of nerve roots in patients with SNN, which can play a significant role in early diagnosis. (orig.)

  20. Increased cortical lesion load and intrathecal inflammation is associated with oligoclonal bands in multiple sclerosis patients: a combined CSF and MRI study.

    Science.gov (United States)

    Farina, Gabriele; Magliozzi, Roberta; Pitteri, Marco; Reynolds, Richard; Rossi, Stefania; Gajofatto, Alberto; Benedetti, Maria Donata; Facchiano, Francesco; Monaco, Salvatore; Calabrese, Massimiliano

    2017-02-21

    Although IgG oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) are a frequent phenomenon in multiple sclerosis (MS) patients, their relationship with grey matter lesions, intrathecal/meningeal inflammation and clinical evolution has not been clarified yet. The aim of our study was to assess the relationship between the OCBs, the inflammatory/neurodegenerative CSF profile at diagnosis, the cortical lesion load and the clinical evolution after 10 years. This is a 10-year observational, cross-sectional study based on a combined MRI, cognitive and CSF profiling of the examined patients. Forty consecutive OCB-negative (OCB-) and 50 OCB-positive (OCB+) MS patients were included in this study. Both groups had mean disease duration of 10 years and were age and gender matched. Each patient underwent neurological and neuropsychological evaluation and 3-T MRI. Analysis of the presence and levels of 28 inflammatory mediators was performed in the CSF obtained from 10 OCB- MS, 11 OCB+ MS and 10 patients with other neurological conditions. Increased number of CLs was found in OCB+ compared to OCB- patients (p TNFSF13B, IL6, IL10) and other pro-inflammatory molecules, such as IFN-γ, TNF, MMP2, GM-CSF, osteopontin and sCD163. Finally, the occurrence of OCB was found associated with poor prognosis, from both physical and cognitive points of view. OCB at MS onset are associated with more severe GM pathology and with a more severe physical disability and cognitive impairment after 10 years. Increased levels of cytokines linked to B cell activation, lymphoid-neogenesis, and pro-inflammatory immune response in the CSF of OCB+ patients support the hypothesis of crucial role played by compartmentalized, intrathecal B cell response in the pathogenesis of CLs and OCB production.

  1. Multiple cystic lung disease.

    Science.gov (United States)

    Ferreira Francisco, Flavia Angélica; Soares Souza, Arthur; Zanetti, Gláucia; Marchiori, Edson

    2015-12-01

    Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt-Hogg-Dubé); other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management. Copyright ©ERS 2015.

  2. Thyroid diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Scriba, P.C.; Boerner, W.; Emrich, S.; Gutekunst, R.; Herrmann, J.; Horn, K.; Klett, M.; Krueskemper, H.L.; Pfannenstiel, P.; Pickardt, C.R.

    1985-03-01

    None of the in-vitro and in-vivo methods listed permits on unambiguous diagnosis when applied alone, owing to the fact that similar or even identical findings are obtained for various individual parameters in different thyroid diseases. Further, especially the in-vitro tests are also subject to extrathyroidal effects which may mask the typical findings. The limited and varying specificity and sensitivity of the tests applied, as well as the falsification of results caused by the patients' idiosyncracies and the methodology, make it necessary to interpret and evaluate the in-vivo and in-vitro findings only if the clinical situation (anamnesis and physical examination) is known. For maximum diagnostic quality of the tests, the initial probability of the assumed type of thyroid disease must be increased (formulation of the clinical problem). The concepts of exclusion diagnosis and identification must be distinguished as well as the diagnosis of functional disturbances on the one hand and of thyroid diseases on the other. Both of this requires a qualified, specific and detailed anamnesis and examination procedure, and the clinical examination remains the obligatory basis of clinical diagnostics. In case of inexplicable discrepancies between the clinical manifestations and the findings obtained with specific methods, or between the findings obtained with a specific method, the patient should be referred to an expert institution, or the expert institution should be consulted.

  3. Ambient diagnostics

    CERN Document Server

    Cai, Yang

    2014-01-01

    Part I. FundamentalsIntroductionWhat is Ambient Diagnostics?Diagnostic ModelsMultimedia IntelligenceCrowd SourcingSoft SensorsScience of SimplicityPersonal DiagnosesBasic AlgorithmsBasic ToolsSummaryProblemsTransformationEarly Discoveries of Heartbeat PatternsTransforms, Features, and AttributesSequential FeaturesSpatiotemporal FeaturesShape FeaturesImagery FeaturesFrequency Domain FeaturesMulti-Resolution FeaturesSummaryProblemsPattern RecognitionSimilarities and DistancesClustering MethodsClassification MethodsClassifier Accuracy MeasuresSummaryProblemsPart II. Multimedia IntelligenceSound RecognitionMicrophone AppsModern Acoustic Transducers (Microphones)Frequency Response CharacteristicsDigital Audio File FormatsHeart Sound SensingLung Sound SensingSnore MeterSpectrogram (STFT)Ambient Sound AnalysisSound RecognitionRecognizing Asthma SoundPeak ShiftFeature CompressionRegroupingNoise IssuesFuture ApplicationsSummaryProblemsColor SensorsColor SensingHuman Color VisionColor SensorsColor Matching ExperimentsC...

  4. Neutron Multiplicity Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Frame, Katherine Chiyoko [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-06-28

    Neutron multiplicity measurements are widely used for nondestructive assay (NDA) of special nuclear material (SNM). When combined with isotopic composition information, neutron multiplicity analysis can be used to estimate the spontaneous fission rate and leakage multiplication of SNM. When combined with isotopic information, the total mass of fissile material can also be determined. This presentation provides an overview of this technique.

  5. Teaching Arithmetic Combinations of Multiplication and Division to Students with Learning Disabilities or Mild Intellectual Disability: The Impact of Alternative Fact Grouping and the Role of Cognitive and Learning Factors

    Science.gov (United States)

    Agaliotis, Ioannis; Teli, Afroditi

    2016-01-01

    The effectiveness of two instructional interventions was investigated in the context of teaching Arithmetic Combinations (ACs) of multiplication and division to students with Learning Disabilities (LD) or Mild Intellectual Disability (MID). The intervention for the control group (LD = 20, MID = 10) was based on principles of effective instruction,…

  6. Combination of the ionic-to-atomic line intensity ratios from two test elements for the diagnostic of plasma temperature and electron number density in Inductively Coupled Plasma Atomic Emission Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Tognoni, E. [Istituto per i Processi Chimico-Fisici, Area della Ricerca del Consiglio Nazionale delle Ricerche Via Moruzzi 1, 56124 Pisa (Italy)], E-mail: tognoni@ipcf.cnr.it; Hidalgo, M.; Canals, A. [Departamento de Quimica Analitica, Nutricion y Bromatologia. Universidad de Alicante. Apdo. 99, 03080, Alicante (Spain); Cristoforetti, G.; Legnaioli, S.; Salvetti, A.; Palleschi, V. [Istituto per i Processi Chimico-Fisici, Area della Ricerca del Consiglio Nazionale delle Ricerche Via Moruzzi 1, 56124 Pisa (Italy)

    2007-05-15

    In Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) spectrochemical analysis, the MgII(280.270 nm)/MgI(285.213 nm) ionic to atomic line intensity ratio is commonly used as a monitor of the robustness of operating conditions. This approach is based on the univocal relationship existing between intensity ratio and plasma temperature, for a pure argon atmospheric ICP in thermodynamic equilibrium. In a multi-elemental plasma in the lower temperature range, the measurement of the intensity ratio may not be sufficient to characterize temperature and electron density. In such a range, the correct relationship between intensity ratio and plasma temperature can be calculated only when the complete plasma composition is known. We propose the combination of the line intensity ratios of two test elements (double ratio) as an effective diagnostic tool for a multi-elemental low temperature LTE plasma of unknown composition. In particular, the variation of the double ratio allows us discriminating changes in the plasma temperature from changes in the electron density. Thus, the effects on plasma excitation and ionization possibly caused by introduction of different samples and matrices in non-robust conditions can be more accurately interpreted. The method is illustrated by the measurement of plasma temperature and electron density in a specific analytic case.

  7. Nanobiosensors in diagnostics

    Directory of Open Access Journals (Sweden)

    Alejandro Chamorro-Garcia

    2016-11-01

    Full Text Available Medical diagnosis has been greatly improved thanks to the development of new techniques capable of performing very sensitive detection and quantifying certain parameters. These parameters can be correlated with the presence of specific molecules and their quantity. Unfortunately, these techniques are demanding, expensive, and often complicated. On the other side, progress in other fields of science and technology has contributed to the rapid growth of nanotechnology. Although being an emerging discipline, nanotechnology has raised huge interest and expectations. Most of the enthusiasm comes from new possibilities and properties of nanomaterials. Biosensors (simple, robust, sensitive, cost-effective combined with nanomaterials, also called nanobiosensors, are serving as bridge between advanced detection/diagnostics and daily/routine tests. Here we review some of the latest applications of nanobiosensors in diagnostics field.

  8. Nitrate source identification in groundwater of