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Sample records for combined multiple intraluminal

  1. Multiple oncocytic cystadenoma with intraluminal crystalloids in parotid gland: case report.

    PubMed

    Başak, Kayhan; Kiroğlu, Kumru

    2014-12-01

    Oncocytic cystadenoma is a benign tumor of salivary glands, histologically characterized by multicystic growth of the oncocytic epithelial lining. Crystals in different shapes and nature associate oncocytic type of salivary gland neoplasms. An 82 year-old woman with right parotideal mass had an operation of superficial parotidectomy. Histological examination revealed multiple unilocular or multilocular cystic lesions with incomplete fibrous capsule, papillary foldings, and 1 or 2 layers of oncocytic epithelium lines. The epithelium lining the cysts were positive for CK8, CK14, CK18, CK19, and negative for SMA, S-100, and p63 immunohistochemically. Cystadenomas were described as mostly multilocular and we presented a multifocal cystic neoplastic lesion lined by oncocytic type epithelial cells with intraluminal crystalloids. Multiple cysts forming morphology, incomplete fibrous capsule of most cysts and immunohistocemical findings were considered as multiple oncocytic cystadenoma with intraluminal crystalloids in the parotid gland.

  2. Intraluminal esophageal diverticulum.

    PubMed

    Funakoshi, O; Soma, Y; Takasugi, T; Munakata, A; Yoshida, Y

    1990-02-01

    An intraluminal esophageal diverticulum (IED) is an uncommon entity defined as a double-layered mucosal pouch lying within the lumen of the esophagus. Its characteristic radiological finding is an intraluminal barium collection surrounded by a radiolucent halo. True IED, which is different from a transient radiological artifact, has not been previously reported in the international literature. This article describes the first case of true IED. Differential diagnosis between a true lesion and a transient flow artifact on barium meal is discussed. PMID:2106464

  3. Combining multiple altimeter missions

    NASA Astrophysics Data System (ADS)

    Jacobs, G. A.; Mitchell, J. L.

    1997-10-01

    Viewing altimeter data only at the points where separate altimeter missions' ground tracks cross provides a method to observe long time period sea surface height (SSH) variations and avoids many of the problems inherent in combining separate altimeter data sets through an independently determined geoid. TOPEX/POSEIDON (T/P) data over the time period from January 1, 1993, to December 31, 1995, form a mean SSH that is used as a reference by other altimeter data sets. A least squares analysis of the mean T/P SSH determines the portion of the Geographically Correlated Orbit Error (GCOE) that may be observed through crossover differences and removes this portion of the GCOE. The analysis removes errors of 0.86 cm RMS at 1 cycle per orbit revolution (cpr) and indicates negligible errors at higher frequencies. After the GCOE removal, the accuracy of the T/P reference mean is better than 1 cm RMS as measured by crossover differences. The GCOE contained in the Geosat-Exact Repeat Mission (ERM) and ERS 1 data with orbit solutions using the Joint Gravity Model (JGM) 3 is evaluated through an adjustment to the T/P reference mean surface. The Geosat-ERM data indicate a bias of about 28 cm averaged over the globe, and the ERS 1 bias is 44 cm. The T/P data used here is not corrected for the oscillator drift correction error so that the actual bias is less by about 13 cm. Both the Geosat-ERM and ERS 1 GCOE are mainly 1 cpr. GCOE estimates at frequencies above 1 cpr indicate little actual orbit error but are more correlated to instrument correction errors (particularly water vapor). Simultaneous T/P and ERS 1 SSH anomalies to the T/P mean indicate good correlation.

  4. Intraluminal biliary obstruction.

    PubMed Central

    Heaton, N D; Davenport, M; Howard, E R

    1991-01-01

    Jaundice caused by intraluminal bile duct obstruction in infancy is rare but may occur in association with biliary sludge, inspissated bile plugs, or gall stones. Nine boys (aged 2 weeks-6 months) with obstruction caused by inspissated bile (n = 7) or gall stones (n = 2) are presented. Haemolysis was not a factor in the patients' histories but an abnormal entry of the common bile duct into the third part of the duodenum was demonstrated in two and one had an asymptomatic haemangioma. Ultrasonography was the most useful investigation. Surgical removal of the bile duct obstruction was necessary in eight cases and included biliary tract drainage in six and cholecystectomy for changes of cholecystitis in four. Obstruction resolved spontaneously in one infant after percutaneous cholangiography. There were no postoperative complications. Images p1396-a PMID:1776884

  5. Intraluminal iodination of thyroglobulin

    SciTech Connect

    Ofverholm, T.; Ericson, L.E.

    1984-03-01

    The intraluminal distribution of newly synthesized (injection of (/sup 3/H)leucine) and newly iodinated (injection of Na/sup 125/I) proteins in thyroids of rats given T4 for 2 days was studied with quantitative electron microscopic autoradiography. Three, 4.5, and 6 h after (/sup 3/H)leucine about 90%, 85%, and 65%, respectively, of the luminal label was confined to the microvillus region. This distribution differed from that of newly iodinated protein; already 2 min after injection only about 30% of the grains was located over the microvillus region. The remaining 70% of the grains located outside the microvillus region formed a gradient towards the center of the lumen. The grain distributions 30 min and 2 h after Na/sup 125/I were similar to that present after 2 min. The distribution of grains after pulse labeling with Na/sup 125/I (injected 2 min before propylthiouracil and 2 h before fixation) was also similar to that found in rats injected with Na/sup 125/I alone, indicating that diffusion of labeled proteins in the lumen was very slow in T4-treated rats. A slow diffusion was also suggested by the presence of an unlabeled peripheral ring in follicle lumens of T4-treated rats injected with Na/sup 125/I 48 h before fixation. In normal rats given (/sup 3/H)leucine 3 h before fixation or Na/sup 125/I 1 h or 48 h before fixation the grains were homogeneously distributed in most follicle lumens. Together our findings indicate that (1) administration of T4 has effects on the diffusion properties of the colloid; (2) iodine is incorporated not only into newly synthesized thyroglobulin recently delivered to the follicle lumen but also into molecules already stored in the lumen; (3) a portion of the iodine incorporated into proteins is bound to molecules which are not in direct contact with thyroperoxidase in the apical plasma membrane.

  6. Intra- and inter-observer reliability of combined segmental measurement techniques for predicting immediate post-deployment intraluminal tracheal stent length in dogs

    PubMed Central

    Monaco, Thomas A.; Taylor, Jim A.; Langenbach, Anke; Gordon, Sebastian; Vance, Eric

    2014-01-01

    This study evaluated segmental measurement techniques for predicting immediate post-deployment intraluminal tracheal stent length in dogs with naturally occurring tracheal collapse. Radiographs of 12 client-owned dogs that underwent intraluminal tracheal stent placement were retrospectively reviewed. Tracheal lengths were divided into 1, 2, 3, or 4 equal segments. Stent lengths were predicted using the widest dorsoventral height of each segment, with and without the addition of 10%, and an accompanying foreshortening chart. Techniques were compared for intra- and inter-observer reliability, and post-deployment stent length predictability. There was good to high intra- and inter-observer reliability for all segmental measurements; median intra-class correlation coefficients were 0.98 and 0.92, respectively. Measuring 2 segments without the addition of 10% to the widths was significantly more accurate in predicting immediate post-deployment stent length in terms of percent (P = 0.03) and absolute difference (P = 0.02). Segmental measuring techniques are repeatable amongst observers and may help guide stent selection. PMID:24790228

  7. Intraluminal fluorescence spectroscopy catheter with ultrasound guidance

    NASA Astrophysics Data System (ADS)

    Stephens, Douglas N.; Park, Jesung; Sun, Yang; Papaioannou, Thanassis; Marcu, Laura

    2009-05-01

    We demonstrate the feasibility of a time-resolved fluorescence spectroscopy (TRFS) technique for intraluminal investigation of arterial vessel composition under intravascular ultrasound (IVUS) guidance. A prototype 1.8-mm (5.4 Fr) catheter combining a side-viewing optical fiber (SVOF) and an IVUS catheter was constructed and tested with in vitro vessel phantoms. The prototype catheter can locate a fluorophore in the phantom vessel wall, steer the SVOF in place, perform blood flushing under flow conditions, and acquire high-quality TRFS data using 337-nm wavelength excitation. The catheter steering capability used for the coregistration of the IVUS image plane and the SVOF beam produce a guiding precision to an arterial phantom wall site location of 0.53+/-0.16 mm. This new intravascular multimodal catheter enables the potential for in vivo arterial plaque composition identification using TRFS.

  8. Intraluminal tissue welding for anastomosis

    DOEpatents

    Glinsky, M.; London, R.; Zimmerman, G.; Jacques, S.

    1998-10-27

    A method and device are provided for performing intraluminal tissue welding for anastomosis of a hollow organ. A retractable catheter assembly is delivered through the hollow organ and consists of a catheter connected to an optical fiber, an inflatable balloon, and a biocompatible patch mounted on the balloon. The disconnected ends of the hollow organ are brought together on the catheter assembly, and upon inflation of the balloon, the free ends are held together on the balloon to form a continuous channel while the patch is deployed against the inner wall of the hollow organ. The ends are joined or ``welded`` using laser radiation transmitted through the optical fiber to the patch. A thin layer of a light-absorbing dye on the patch can provide a target for welding. The patch may also contain a bonding agent to strengthen the bond. The laser radiation delivered has a pulse profile to minimize tissue damage. 8 figs.

  9. Intraluminal tissue welding for anastomosis

    DOEpatents

    Glinsky, Michael; London, Richard; Zimmerman, George; Jacques, Steven

    1998-10-27

    A method and device are provided for performing intraluminal tissue welding for anastomosis of a hollow organ. A retractable catheter assembly is delivered through the hollow organ and consists of a catheter connected to an optical fiber, an inflatable balloon, and a biocompatible patch mounted on the balloon. The disconnected ends of the hollow organ are brought together on the catheter assembly, and upon inflation of the balloon, the free ends are held together on the balloon to form a continuous channel while the patch is deployed against the inner wall of the hollow organ. The ends are joined or "welded" using laser radiation transmitted through the optical fiber to the patch. A thin layer of a light-absorbing dye on the patch can provide a target for welding. The patch may also contain a bonding agent to strengthen the bond. The laser radiation delivered has a pulse profile to minimize tissue damage.

  10. Novel Combination Treatments in Multiple Myeloma.

    PubMed

    Nooka, Ajay K; Lonial, Sagar

    2016-05-01

    The last decade has witnessed the identification of several novel druggable targets in multiple myeloma, leading to identification of novel therapies with clinically proven efficacy, both in the newly diagnosed and relapsed setting. More importantly, a common theme of good outcomes was observed among prospective randomized studies that have utilized combinations of agents with different mechanisms of action. The correlation between achieving a deeper response and the improvement in progression-free survival and overall survival has never been so clear. In this article, we elucidate the rationale for use of novel drug combinations in patients with myeloma, and review current evidence-based data supporting the use of specific combinations in various settings. We also attempt to craft a framework to guide clinicians in optimizing the use of combination therapies, to enable patients to derive maximal benefit. PMID:27188677

  11. 21 CFR 870.4875 - Intraluminal artery stripper.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intraluminal artery stripper. 870.4875 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4875 Intraluminal artery stripper. (a) Identification. An intraluminal artery stripper is a device used to perform an...

  12. 21 CFR 870.4875 - Intraluminal artery stripper.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Intraluminal artery stripper. 870.4875 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4875 Intraluminal artery stripper. (a) Identification. An intraluminal artery stripper is a device used to perform an...

  13. 21 CFR 870.4875 - Intraluminal artery stripper.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Intraluminal artery stripper. 870.4875 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4875 Intraluminal artery stripper. (a) Identification. An intraluminal artery stripper is a device used to perform an...

  14. 21 CFR 870.4875 - Intraluminal artery stripper.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Intraluminal artery stripper. 870.4875 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4875 Intraluminal artery stripper. (a) Identification. An intraluminal artery stripper is a device used to perform an...

  15. 21 CFR 870.4875 - Intraluminal artery stripper.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Intraluminal artery stripper. 870.4875 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4875 Intraluminal artery stripper. (a) Identification. An intraluminal artery stripper is a device used to perform an...

  16. Combining Multiple Gyroscope Outputs for Increased Accuracy

    NASA Technical Reports Server (NTRS)

    Bayard, David S.

    2003-01-01

    A proposed method of processing the outputs of multiple gyroscopes to increase the accuracy of rate (that is, angular-velocity) readings has been developed theoretically and demonstrated by computer simulation. Although the method is applicable, in principle, to any gyroscopes, it is intended especially for application to gyroscopes that are parts of microelectromechanical systems (MEMS). The method is based on the concept that the collective performance of multiple, relatively inexpensive, nominally identical devices can be better than that of one of the devices considered by itself. The method would make it possible to synthesize the readings of a single, more accurate gyroscope (a virtual gyroscope) from the outputs of a large number of microscopic gyroscopes fabricated together on a single MEMS chip. The big advantage would be that the combination of the MEMS gyroscope array and the processing circuitry needed to implement the method would be smaller, lighter in weight, and less power-hungry, relative to a conventional gyroscope of equal accuracy. The method (see figure) is one of combining and filtering the digitized outputs of multiple gyroscopes to obtain minimum-variance estimates of rate. In the combining-and-filtering operations, measurement data from the gyroscopes would be weighted and smoothed with respect to each other according to the gain matrix of a minimum- variance filter. According to Kalman-filter theory, the gain matrix of the minimum-variance filter is uniquely specified by the filter covariance, which propagates according to a matrix Riccati equation. The present method incorporates an exact analytical solution of this equation.

  17. Three allele combinations associated with Multiple Sclerosis

    PubMed Central

    Favorova, Olga O; Favorov, Alexander V; Boiko, Alexey N; Andreewski, Timofey V; Sudomoina, Marina A; Alekseenkov, Alexey D; Kulakova, Olga G; Gusev, Eugenyi I; Parmigiani, Giovanni; Ochs, Michael F

    2006-01-01

    Background Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. Methods 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion) of the DRB1, TNF, LT, TGFβ1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. Results We identified two previously unknown MS-associated tri-allelic combinations: -509TGFβ1*C, DRB1*18(3), CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2) allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Δ32, DRB1*04 were also reidentified as MS-associated. Conclusion These results represent an independent validation of MS association with DRB1*15(2) and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles. PMID:16872485

  18. Optimal combination of multiple cortical surface parcellations

    NASA Astrophysics Data System (ADS)

    Hu, Xintao; Guo, Lei; Li, Gang; Li, Kaiming; Liu, Tianming

    2010-03-01

    A variety of methodologies have been developed for the parcellation of human cortical surface into sulcal or gyral regions due to its importance in structural and functional mapping of the human brain. However, characterizing the performance of surface parcellation methods and the estimation of ground truth of segmentation are still open problems. In this paper, we present an algorithm for simultaneous truth and performance estimation of various approaches for human cortical surface parcellation. The probabilistic true segmentation is estimated as a weighted combination of the segmentations resulted from multiple methods. Afterward, an Expectation-Maximization (EM) algorithm is used to optimize the weighting depending on the estimated performance level of each method. Furthermore, a spatial homogeneity constraint modeled by the Hidden Markov Random Field (HMRF) theory is incorporated to refine the estimated true segmentation into a spatially homogenous decision. The proposed method has been evaluated using both synthetic and real data. The experimental results demonstrate the validity of the method proposed in this paper. Also, it has been used to generate reference sulci regions to perform a comparison study of three methods for cortical surface parcellation.

  19. Combining Multiple Pairwise Structure-based Alignments

    SciTech Connect

    2014-11-12

    CombAlign is a new Python code that generates a gapped, one-to-many, multiple structure-based sequence alignment(MSSA) given a set of pairwise structure-based alignments. In order to better define regions of similarity among related protein structures, it is useful to detect the residue-residue correspondences among a set of pairwise structure alignments. Few codes exist for constructing a one-to-many, multiple sequence alignment derived from a set of structure alignments, and we perceived a need for creating a new tool for combing pairwise structure alignments that would allow for insertion of gaps in the reference structure.

  20. Combining Multiple Pairwise Structure-based Alignments

    2014-11-12

    CombAlign is a new Python code that generates a gapped, one-to-many, multiple structure-based sequence alignment(MSSA) given a set of pairwise structure-based alignments. In order to better define regions of similarity among related protein structures, it is useful to detect the residue-residue correspondences among a set of pairwise structure alignments. Few codes exist for constructing a one-to-many, multiple sequence alignment derived from a set of structure alignments, and we perceived a need for creating a newmore » tool for combing pairwise structure alignments that would allow for insertion of gaps in the reference structure.« less

  1. Endophthalmitis associated with Glaucoma Shunt Intraluminal Stent Exposure.

    PubMed

    Kwon, Hye Jin; Kerr, Nathan M; Ruddle, Jonathan B; Ang, Ghee Soon

    2016-01-01

    Endophthalmitis post glaucoma drainage implant (GDI) surgery is rare, often associated with tube or plate exposure. We report a case of endophthalmitis following glaucoma shunt intraluminal stent exposure in a patient who underwent Baerveldt glaucoma implant surgery. Endophthalmitis following manipulation of intraluminal stents is a rare complication of GDIs but potentially vision threatening condition that needs to be carefully screened for and treated immediately. How to cite this article: Kwon HJ, Kerr NM, Ruddle JB, Ang GS. Endophthalmitis associated with Glaucoma Shunt Intraluminal Stent Exposure. J Curr Glaucoma Pract 2016;10(1):36-37.

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

    ERIC Educational Resources Information Center

    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…

  3. Intraluminal tracheal stent fracture in a Yorkshire terrier.

    PubMed

    Woo, Heung-Myong; Kim, Mi-Jeong; Lee, Seung-Gon; Nam, Hyun-Sook; Kwak, Ho-Hyun; Lee, Joon-Seok; Park, In-Chul; Hyun, Changbaig

    2007-10-01

    An 8-year-old Yorkshire terrier was presented with tracheal collapse. Two intraluminal nitinol stents were implanted. The implanted stents were found to be fractured 4 weeks after implantation. The fractured stents were removed. To restore the collapsed trachea, ring prostheses were applied. However, the dog was euthanized because of a bad outcome following surgery.

  4. Combining results of multiple search engines in proteomics.

    PubMed

    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.

  5. Recurrent Giant Cell Tumor of Skull Combined with Multiple Aneurysms

    PubMed Central

    Kim, Dae Hwan

    2016-01-01

    Giant cell tumors are benign but locally invasive and frequently recur. Giant cell tumors of the skull are extremely rare. A patient underwent a surgery to remove a tumor, but the tumor recurred. Additionally, the patient developed multiple aneurysms. The patient underwent total tumor resection and trapping for the aneurysms, followed by radiotherapy. We report this rare case and suggest some possibilities for treating tumor growth combined with aneurysm development. PMID:27195256

  6. Nanoparticle Based Combination Treatments for Targeting Multiple Hallmarks of Cancer

    PubMed Central

    VanDyke, D; Kyriacopulos, P; Yassini, B; Wright, A; Burkhart, E; Jacek, S; Pratt, M; Peterson, CR; Rai, P

    2016-01-01

    Treatment of cancer remains one of the most challenging tasks facing the healthcare system. Cancer affects the lives of millions of people and is often fatal. Current treatment methods include surgery, chemotherapy, radiation therapies or some combinations of these. However, recurrence is a major problem. These treatments can be invasive with severe side effects. Inefficacies in treatments are a result of the complex and variable biology of cancerous cells. Malignant tumor cells and normal functioning cells share many of the same biological characteristics but the main difference is that in cancer cells there is in an overuse and over expression of these biological characteristics. These pertinent characteristics can be grouped into eight hallmarks, as illustrated by Hanahan and Weinberg. These characteristics include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism, and evading immune destruction. In order to provide a noninvasive, effective treatment, delivery methods must be explored in order to transport cytotoxic agents used for targeting the hallmarks of cancer in a safer and more effective fashion. The use of nanoparticles as drug delivery carriers provides an effective method in which multiple cytotoxic agents can be safely delivered to cancer tissue to simultaneously target multiple hallmarks. By targeting multiple hallmarks of cancer at once, the efficacy of cancer treatments could be improved drastically. This review explores the uses and efficacy of combination therapies using nanoparticles that can simultaneously target multiple hallmarks of cancer. PMID:27547592

  7. Missed appendicitis: did unexpected intraluminal densities play a role?

    PubMed

    Harper, Rachel; Friedman, Benjamin T; Strote, Jared

    2016-01-01

    A healthy 19-year-old boy presented to our emergency department with abdominal pain. His history, examination and laboratory evaluation raised concern for appendicitis. A CT study of the abdomen and pelvis was carried out by the radiologist and emergency physician and was notable only for a large amount of unexpected high-attenuation intraluminal material. With further history, this was thought to be most likely retained bismuth from over-the-counter medicine ingestion. The patient was discharged home without a diagnosis. Further review of the CT scan by a second radiologist revealed a concern for appendiceal enlargement and associated free fluid. The patient was called back for further evaluation and treatment and ultimately an appendectomy was performed. Physicians should be aware of the causes and impact of unexpected radiopaque intraluminal contents on radiological studies. Most commonly from ingested medicine, such findings can obscure mucosal details, mimic active bleeding or create a distraction from other abnormalities. PMID:27605197

  8. A Phased Approach for Assessing Combined Effects from Multiple Stressors

    PubMed Central

    Menzie, Charles A.; MacDonell, Margaret M.; Mumtaz, Moiz

    2007-01-01

    We present a phased approach for evaluating the effects of physical, biological, chemical, and psychosocial stressors that may act in combination. Although a phased concept is common to many risk-based approaches, it has not been explicitly outlined for the assessment of combined effects of multiple stressors. The approach begins with the development of appropriate conceptual models and assessment end points. The approach then proceeds through a screening stage wherein stressors are evaluated with respect to their potential importance as contributors to risk. Stressors are considered individually or as a combination of independent factors with respect to one or more common assessment end points. As necessary, the approach then proceeds to consider interactions among stressors. We make a distinction between applications that begin with effects of concern (effects based) or with specific stressors (stressor based). We describe a number of tools for use within the phased approach. The methods profiled are ones that have been applied to yield results that can be communicated to a wide audience. The latter characteristic is considered especially important because multiple stressor problems usually involve exposures to communities or to ecologic regions with many stakeholders. PMID:17520072

  9. An approach for combining multiple descriptors for image classification

    NASA Astrophysics Data System (ADS)

    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.

  10. Knowing the crowd within: Metacognitive limits on combining multiple judgments.

    PubMed

    Fraundorf, Scott H; Benjamin, Aaron S

    2014-02-01

    We investigated how decision-makers use multiple opportunities to judge a quantity. Decision-makers undervalue the benefit of combining their own judgment with an advisor's, but theories disagree about whether this bias would apply to combining several of one's own judgments. Participants estimated percentage answers to general knowledge questions (e.g., What percent of the world's population uses the Internet?) on two occasions. In a final decision phase, they selected their first, second, or average estimate to report for each question. We manipulated the cues available for this final decision. Given cues to general theories (the labels first guess, second guess, average), participants mostly averaged, but no more frequently on trials where the average was most accurate. Given item-specific cues (numerical values of the options), metacognitive accuracy was at chance. Given both cues, participants mostly averaged and switched strategies based on whichever yielded the most accurate value on a given trial. These results indicate that underappreciation of averaging estimates does not stem only from social differences between the self and an advisor and that combining general and item-specific cues benefits metacognition.

  11. Combining multiple thresholding binarization values to improve OCR output

    NASA Astrophysics Data System (ADS)

    Lund, William B.; Kennard, Douglas J.; Ringger, Eric K.

    2013-01-01

    For noisy, historical documents, a high optical character recognition (OCR) word error rate (WER) can render the OCR text unusable. Since image binarization is often the method used to identify foreground pixels, a body of research seeks to improve image-wide binarization directly. Instead of relying on any one imperfect binarization technique, our method incorporates information from multiple simple thresholding binarizations of the same image to improve text output. Using a new corpus of 19th century newspaper grayscale images for which the text transcription is known, we observe WERs of 13.8% and higher using current binarization techniques and a state-of-the-art OCR engine. Our novel approach combines the OCR outputs from multiple thresholded images by aligning the text output and producing a lattice of word alternatives from which a lattice word error rate (LWER) is calculated. Our results show a LWER of 7.6% when aligning two threshold images and a LWER of 6.8% when aligning five. From the word lattice we commit to one hypothesis by applying the methods of Lund et al. (2011) achieving an improvement over the original OCR output and a 8.41% WER result on this data set.

  12. Effect of intraluminal pillars on particle motion in bifurcated microchannels.

    PubMed

    Turhan, Aslihan; Tsuda, Akira; Konerding, Moritz A; Lin, Miao; Miele, Lino; Lee, Grace; Mentzer, Steven J

    2008-01-01

    A central feature of intussusceptive angiogenesis is the development of an intravascular pillar that bridges the opposing sides of the microvessel lumen. In this report, we created polydimethyl siloxane (PDMS) microchannels with geometric proportions based on corrosion casts of the colon microcirculation. The structure of the PDMS microchannels was a bifurcated channel with an intraluminal pillar in the geometric center of the bifurcation. The effect of the intraluminal pillar on particle flow paths was investigated using an in vitro perfusion system. The microchannels were perfused with fluorescent particles, and the particle movements were recorded using fluorescence videomicroscopy. We found that the presence of an intravascular pillar significantly decreased particle velocity in the bifurcation system (p < 0.05). In addition, the pillar altered the trajectory of particles in the center line of the flow stream. The particle trajectory resulted in prolonged pillar contact as well as increased residence time within the bifurcation system (p < 0.001). Our results suggest that the intravascular pillar not only provides a mechanism of increasing resistance to blood flow but may also participate in spatial redistribution of cells within the flow stream.

  13. Combining fractional polynomial model building with multiple imputation.

    PubMed

    Morris, Tim P; White, Ian R; Carpenter, James R; Stanworth, Simon J; Royston, Patrick

    2015-11-10

    Multivariable fractional polynomial (MFP) models are commonly used in medical research. The datasets in which MFP models are applied often contain covariates with missing values. To handle the missing values, we describe methods for combining multiple imputation with MFP modelling, considering in turn three issues: first, how to impute so that the imputation model does not favour certain fractional polynomial (FP) models over others; second, how to estimate the FP exponents in multiply imputed data; and third, how to choose between models of differing complexity. Two imputation methods are outlined for different settings. For model selection, methods based on Wald-type statistics and weighted likelihood-ratio tests are proposed and evaluated in simulation studies. The Wald-based method is very slightly better at estimating FP exponents. Type I error rates are very similar for both methods, although slightly less well controlled than analysis of complete records; however, there is potential for substantial gains in power over the analysis of complete records. We illustrate the two methods in a dataset from five trauma registries for which a prognostic model has previously been published, contrasting the selected models with that obtained by analysing the complete records only.

  14. A hybrid-perturbation-Galerkin technique which combines multiple expansions

    NASA Technical Reports Server (NTRS)

    Geer, James F.; Andersen, Carl M.

    1989-01-01

    A two-step hybrid perturbation-Galerkin method for the solution of a variety of differential equations type problems is found to give better results when multiple perturbation expansions are employed. The method assumes that there is parameter in the problem formulation and that a perturbation method can be sued to construct one or more expansions in this perturbation coefficient functions multiplied by computed amplitudes. In step one, regular and/or singular perturbation methods are used to determine the perturbation coefficient functions. The results of step one are in the form of one or more expansions each expressed as a sum of perturbation coefficient functions multiplied by a priori known gauge functions. In step two the classical Bubnov-Galerkin method uses the perturbation coefficient functions computed in step one to determine a set of amplitudes which replace and improve upon the gauge functions. The hybrid method has the potential of overcoming some of the drawbacks of the perturbation and Galerkin methods as applied separately, while combining some of their better features. The proposed method is applied, with two perturbation expansions in each case, to a variety of model ordinary differential equations problems including: a family of linear two-boundary-value problems, a nonlinear two-point boundary-value problem, a quantum mechanical eigenvalue problem and a nonlinear free oscillation problem. The results obtained from the hybrid methods are compared with approximate solutions obtained by other methods, and the applicability of the hybrid method to broader problem areas is discussed.

  15. Three-Drug Combination for Relapsed Multiple Myeloma

    Cancer.gov

    A summary of Interim results from an international, randomized phase III trial that suggest that adding carfilzomib (Kyprolis®) to a standard treatment improves outcomes for patients with multiple myeloma whose cancer has relapsed.

  16. Is there something special with probabilities?--insight vs. computational ability in multiple risk combination.

    PubMed

    Juslin, Peter; Lindskog, Marcus; Mayerhofer, Bastian

    2015-03-01

    While a wealth of evidence suggests that humans tend to rely on additive cue combination to make controlled judgments, many of the normative rules for probability combination require multiplicative combination. In this article, the authors combine the experimental paradigms on probability reasoning and multiple-cue judgment to allow a comparison between formally identical tasks that involve probability vs. other task contents. The purpose was to investigate if people have cognitive algorithms for the combination, specifically, of probability, affording multiplicative combination in the context of probability. Three experiments suggest that, although people show some signs of a qualitative understanding of the combination rules that are specific to probability, in all but the simplest cases they lack the cognitive algorithms needed for multiplication, but instead use a variety of additive heuristics to approximate the normative combination. Although these heuristics are surprisingly accurate, normative combination is not consistently achieved until the problems are framed in an additive way.

  17. Is there something special with probabilities?--insight vs. computational ability in multiple risk combination.

    PubMed

    Juslin, Peter; Lindskog, Marcus; Mayerhofer, Bastian

    2015-03-01

    While a wealth of evidence suggests that humans tend to rely on additive cue combination to make controlled judgments, many of the normative rules for probability combination require multiplicative combination. In this article, the authors combine the experimental paradigms on probability reasoning and multiple-cue judgment to allow a comparison between formally identical tasks that involve probability vs. other task contents. The purpose was to investigate if people have cognitive algorithms for the combination, specifically, of probability, affording multiplicative combination in the context of probability. Three experiments suggest that, although people show some signs of a qualitative understanding of the combination rules that are specific to probability, in all but the simplest cases they lack the cognitive algorithms needed for multiplication, but instead use a variety of additive heuristics to approximate the normative combination. Although these heuristics are surprisingly accurate, normative combination is not consistently achieved until the problems are framed in an additive way. PMID:25514208

  18. Selective endothelin A receptor antagonism with sitaxentan reduces neointimal lesion size in a mouse model of intraluminal injury

    PubMed Central

    Duthie, Karolina M; Hadoke, Patrick W F; Kirkby, Nicholas S; Miller, Eileen; Ivy, Jessica R; McShane, John F; Lim, Win Gel; Webb, David J

    2015-01-01

    Background and Purpose Endothelin (ET) receptor antagonism reduces neointimal lesion formation in animal models. This investigation addressed the hypothesis that the selective ETA receptor antagonist sitaxentan would be more effective than mixed ETA/B receptor antagonism at inhibiting neointimal proliferation in a mouse model of intraluminal injury. Experimental Approach Antagonism of ETA receptors by sitaxentan (1–100 nM) was assessed in femoral arteries isolated from adult, male C57Bl6 mice using isometric wire myography. Neointimal lesion development was induced by intraluminal injury in mice receiving sitaxentan (ETA antagonist; 15 mg·kg−1·day−1), A192621 (ETB antagonist; 30 mg·kg−1·day−1), the combination of both antagonists or vehicle. Treatment began 1 week before, and continued for 28 days after, surgery. Femoral arteries were then harvested for analysis of lesion size and composition. Key Results Sitaxentan produced a selective, concentration-dependent parallel rightward shift of ET-1-mediated contraction in isolated femoral arteries. Sitaxentan reduced neointimal lesion size, whereas ETB and combined ETA/B receptor antagonism did not. Macrophage and α-smooth muscle actin content were unaltered by ET receptor antagonism but sitaxentan reduced the amount of collagen in lesions. Conclusions and Implications These results suggest that ETA receptor antagonism would be more effective than combined ETA/ETB receptor antagonism at reducing neointimal lesion formation. PMID:25598351

  19. Salivary oncocytic cystadenoma with intraluminal crystalloids: a case report with review of the literature.

    PubMed

    Bezić, Joško; Glavina-Durdov, Merica

    2011-12-01

    Oncocytic cystadenoma is a rare benign tumor of major salivary glands that in rare occasions may present histologically with intraluminal crystalloids. We report a case of 53-year-old man with a progressively enlarging lump in the left submandibular region. Ultrasound examination revealed a cystic mass with an intraluminal fluid collection. The tumor was surgically removed. Histologic examination yielded a diagnosis of oncocytic cystadenoma with a high concentration of intraluminal crystalloids. The microscopic features of the crystalloids were compatible with nontyrosine (alpha-amylase) crystalloids. When compared with previously published cases in the literature, this is the first report of oncocytic cystadenoma with intraluminal crystalloids arising in the submandibular gland, and the second reported case of the nontyrosine type of crystalloids occurring in association with this tumor. The nontyrosine crystalloids may be highly characteristic to salivary gland tumors with oncocytic differentiation.

  20. Analysis of the ICE combiner for multiple antenna arraying

    NASA Technical Reports Server (NTRS)

    Foster, C.; Marina, M.

    1987-01-01

    The passage of the International Cometary Explorer (ICE) through the tail of comet Giacobini-Zinner took place on September 11, 1985, at approximately 11:04 GMT. The signal-to-noise ratio of the data received from the ICE spacecraft during the comet encounter was improved by arraying the 64-m antenna channels A and B (RCP and LCP) with the two 34-m antennas. Specially designed combiners were built to combine the signals received by the three antennas at the different DSN sites to ensure that the spacecraft's weak signal was received. Although the ICE spacecraft was built with a 5-W transmitter and with a small antenna designed to provide data from no farther than 1 million miles, these combiners provided enough signal margin during the encounter to receive the ICE transmitted data from within the tail of comet Giacobini-Zinner, 44 million miles from earth.

  1. [A CASE OF ASCENDING COLON CANCER RECURRENCE WITH INTRALUMINAL URETERAL DISSEMINATION MIMICKING PRIMARY URETERAL CANCER, DETECTED DURING INVESTIGATION FOR FEVER].

    PubMed

    Nishiyama, Ryuichi; Kubota, Masashi; Kanno, Toru; Okada, Takashi; Higashi, Yoshihito; Yamada, Hitoshi

    2015-10-01

    A 69-year-old woman visited our hospital with a chief complaint of fever. Five years ago, she was diagnosed as ascending colon cancer and received right hemi-colectomy. One year later, local recurrence with right hydronephrosis was detected, and she received chemotherapy -4 cycles of modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab, and 12 cycles of fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab- for two years. Local recurrence and right hydronephrosis disappeared on positron emission tomography performed 4 years postoperatively. This time, abdominal computed tomography for investigation of fever showed a relapse of right hydronephrosis and pyonephrosis. Cystoscopy revealed non-papillary tumor from the right ureteral orifice. Pelvic magnetic resonance imaging showed multiple tumors in the right ureter, and the distal lesion projecting into the bladder. After the general condition became well by right nephrostomy for infection control, transurethral resection of bladder tumor was performed. Histological examination of the specimen revealed a metastatic tubular adenocarcinoma (colon origin). Although right nephrectomy was performed for pyonephrosis control, she died of local progression of ascending colon cancer 10 months after first visit. Intraluminal ureteral progression of carcinoma originating from organs other than urinary tract is very rare. To our knowledge, this is the 9th report in the English or Japanese literature. In this case we could not rule out primary ureteral cancer preoperatively, and histological examination revealed intraluminal ureteral dissemination of ascending colon cancer.

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

    ERIC Educational Resources Information Center

    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…

  3. Diamagnetically stabilized levitation control of an intraluminal magnetic capsule.

    PubMed

    Lam, Michael; Mintchev, Martin

    2009-08-01

    Controlled navigation promotes full utilization of capsule endoscopy for reliable real-time diagnosis in the gastrointestinal (GI) tract, but intermittent natural peristalsis can disturb the navigational control, destabilize the capsule and take it out of levitation. The focus of the present work was to develop an economical and effective real-time magnetic capsule-guiding system that can operate in the presence of naturally existing peristalsis while retaining navigational control. A real-size magnetic navigation system that can handle peristaltic forces of up to 1.5 N was designed utilizing the computer-aided design (CAD) system Maxwell 3D (Ansoft, Pittsburg, PA) and was verified using a small-size physical experimental setup. The proposed system contains a pair of 50 cm diameter, 10,000-turn copper electromagnets with a 10 cm x 10 cm ferrous core driven by currents of up to 300 A and can successfully maintain position control over the levitating capsule during peristalsis. The addition of bismuth diamagnetic casing for stabilizing the levitating capsule was also studied. A modeled magnetic field around the diamagnetically cased permanent magnet was shown to be redistributed aligning its interaction with the external electromagnets, thus stabilizing the levitating capsule. In summary, a custom-designed diamagnetically facilitated capsule navigation system can successfully steer an intraluminal magnet-carrying capsule. PMID:19550023

  4. Symptomatic Patients with Intraluminal Carotid Thrombus: Outcome with a Strategy of Initial Anticoagulation

    PubMed Central

    Vellimana, Ananth K.; Kadkhodayan, Yasha; Rich, Keith M.; Cross, Dewitte T.; Moran, Christopher J.; Zazulia, Allyson R.; Lee, Jin-Moo; Chicoine, Michael R.; Dacey, Ralph G.; Derdeyn, Colin P.; Zipfel, Gregory J.

    2013-01-01

    Background Optimal treatment for patients with symptomatic intraluminal carotid thrombus (ICT) remains poorly defined. Methods We performed a retrospective chart review of patients presenting to our institution between 2001 and 2011 with symptomatic ICT. Results Twenty-four patients (16 males, 8 females) with ICT presented with ischemic stroke (n=18) or TIA (n=6). All were treated initially with anticoagulation ± antiplatelet drugs. Eight of these patients had no or mild carotid stenosis on initial angiography and were treated with medical management alone. The remaining 16 patients had moderate or severe carotid stenosis on initial angiography. Of these, 10 underwent delayed revascularization (endarterectomy, n=8; angioplasty and stenting, n=2), 2 refused revascularization, and 4 were treated with medical therapy alone. One patient had multiple TIAs despite medical therapy and eventually underwent CEA; the remaining 23 patients had no TIAs. No patient suffered ischemic or hemorrhagic stroke while on anticoagulation, during the perioperative period or in long-term follow up; one patient died of an unrelated condition (mean follow-up = 16.4 months). Conclusion Our results suggest that initial anticoagulation of symptomatic ICT results in a low rate of recurrent ischemic events and that carotid revascularization, if indicated, can be safely performed in a delayed manner. PMID:23061393

  5. Ranking and combining multiple predictors without labeled data

    PubMed Central

    Parisi, Fabio; Strino, Francesco; Nadler, Boaz; Kluger, Yuval

    2014-01-01

    In a broad range of classification and decision-making problems, one is given the advice or predictions of several classifiers, of unknown reliability, over multiple questions or queries. This scenario is different from the standard supervised setting, where each classifier’s accuracy can be assessed using available labeled data, and raises two questions: Given only the predictions of several classifiers over a large set of unlabeled test data, is it possible to (i) reliably rank them and (ii) construct a metaclassifier more accurate than most classifiers in the ensemble? Here we present a spectral approach to address these questions. First, assuming conditional independence between classifiers, we show that the off-diagonal entries of their covariance matrix correspond to a rank-one matrix. Moreover, the classifiers can be ranked using the leading eigenvector of this covariance matrix, because its entries are proportional to their balanced accuracies. Second, via a linear approximation to the maximum likelihood estimator, we derive the Spectral Meta-Learner (SML), an unsupervised ensemble classifier whose weights are equal to these eigenvector entries. On both simulated and real data, SML typically achieves a higher accuracy than most classifiers in the ensemble and can provide a better starting point than majority voting for estimating the maximum likelihood solution. Furthermore, SML is robust to the presence of small malicious groups of classifiers designed to veer the ensemble prediction away from the (unknown) ground truth. PMID:24474744

  6. Multichannel intraluminal impedance and esophageal manometry data for unrestricted swallowing: establishing normal values.

    PubMed

    Wilson, J A; Mainie, I; Tutuian, R; Agrawal, A; Castell, D O

    2008-01-01

    Standard esophageal manometric testing evaluates swallowing in the supine position using small boluses, with a recovery period imposed between swallows. Manometric tests of more physiologic unrestricted swallowing have had limited practical application due to highly variable results. The purpose of this study is to apply multichannel intraluminal impedance and manometry (MII-EM) to test esophageal function during unrestricted upright meal consumption, and to assess results in a normal healthy population. Ten healthy volunteers with normal esophageal impedance and manometry by published criteria underwent MII-EM testing using a combined 5-channel catheter. After transnasal placement of the catheter, each subject sat upright and consumed a meal that consisted of two pieces of toasted bread and two ounces of Gatorade. There were no restrictions placed on chewing, swallowing, or eating time. All data assessed by the MII-EM meal test were normally distributed. Impedance results with limited variability included the meal duration, number of swallows, postprandial emptying time and the percent of bolus presence times at 15, 10, and 5 cm above the lower esophageal sphincter. Manometric results with limited variability included the number of peristaltic sequences, mean time between these sequences and their distal esophageal amplitudes. MII-EM can be used to collect data with minimal variability in healthy subjects during unrestricted upright meal consumption. This technique may be used to identify abnormal motility patterns during physiologic swallowing. PMID:18197939

  7. Intraluminal Meckel's Duplication Cyst Causing Bowel Obstruction in an Infant: A Role for Laparotomy

    PubMed Central

    Garcia, Alejandro V.; Allison, Derek B.; Lukish, Jeffrey R.

    2016-01-01

    This report describes a two-month-old girl who presented with signs and symptoms of a distal small bowel obstruction. She underwent an abdominal ultrasound that revealed a right lower quadrant cystic mass. A Technetium-99 scan revealed increased activity in the right lower quadrant consistent with a Meckel's diverticulum. Following a nondiagnostic laparoscopic evaluation, a laparotomy was performed to allow direct palpation of the small bowel and colon. Direct palpation of the ileum revealed a soft intraluminal mass at the ileocecal valve. The child underwent an ileocecectomy and anastomosis incorporating the intraluminal mass. Pathologic analysis revealed an intraluminal enteric duplication cyst containing ectopic gastric mucosa. This case represents the first report of such an entity in an infant. A discussion of the diagnostic and therapeutic aspects of the case and enteric duplication cysts is provided.

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

    ERIC Educational Resources Information Center

    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…

  9. A new sensitizer DVDMS combined with multiple focused ultrasound treatments: an effective antitumor strategy

    NASA Astrophysics Data System (ADS)

    Xiong, Wenli; Wang, Pan; Hu, Jianmin; Jia, Yali; Wu, Lijie; Chen, Xiyang; Liu, Quanhong; Wang, Xiaobing

    2015-12-01

    Sonodynamic therapy (SDT) was developed as a promising noninvasive approach. The present study investigated the antitumor effect of a new sensitizer (sinoporphyrin sodium, referred to as DVDMS) combined with multiple ultrasound treatments on sarcoma 180 both in vitro and in vivo. The combined treatment significantly suppressed cell viability, potentiated apoptosis, and markedly inhibited angiogenesis in vivo. In vivo, the tumor weight inhibition ratio reached 89.82% fifteen days after three sonication treatments plus DVDMS. This effect was stronger than one ultrasound alone (32.56%) and than one round of sonication plus DVDMS (59.33%). DVDMS combined with multiple focused ultrasound treatments initiated tumor tissue destruction, induced cancer cell apoptosis, inhibited tumor angiogenesis, suppressed cancer cell proliferation, and decreased VEGF and PCNA expression levels. Moreover, the treatment did not show obvious signs of side effects or induce a drop in body weight. These results indicated that DVDMS combined with multiple focused ultrasounds may be a promising strategy against solid tumor.

  10. Repositioning and steering laser beam power via coherent combination of multiple Airy beams.

    PubMed

    Zhang, Ze; Ye, Zhuoyi; Song, Daohong; Zhang, Peng; Chen, Zhigang

    2013-12-10

    We study numerically and experimentally laser coherent combination (LCC) with multiple one- or two-dimensional Airy beams. It is shown that the method of LCC using Airy beams leads to a higher combining efficiency and a better feature of propagation than that using conventional Gaussian beams. Based on such coherent Airy beams combination, we propose a laser steering approach that could achieve large-angle beam steering (over 0.6°) without the need of using any mechanical steering component.

  11. Scintigraphic method for the assessment of intraluminal volume and motility of isolated intestinal segments. [Dogs

    SciTech Connect

    Mitchell, A.; Macey, D.J.; Collin, J.

    1983-07-01

    The isolated in vivo intestinal segment is a popular experimental preparation for the investigation of intestinal function, but its value has been limited because no method has been available for measuring changes in intraluminal volume under experimental conditions. We report a scintigraphic technique for measuring intraluminal volume and assessing intestinal motility. Between 30 and 180 ml, the volume of a 75-cm segment of canine jejunum, perfused with Tc-99m-labeled tin colloid, was found to be proportional to the recorded count rate. This method has been used to monitor the effects of the hormone vasopressin on intestinal function.

  12. Correlation between reflux and multichannel intraluminal impedance pH monitoring in untreated volunteers

    PubMed Central

    Jetté, Marie E.; Gaumnitz, Eric A.; Birchall, Martin A.; Welham, Nathan V.; Thibeault, Susan L.

    2014-01-01

    Objective While probable causative agents have been identified (e.g., refluxate components, tobacco smoke), the definitive mechanism for inflammation-related laryngeal mucosal damage remains elusive. Multichannel intraluminal impedance combined with pH monitoring (MII/pH) has emerged as a sensitive tool for diagnosis and characterization of gastroesophageal reflux disease (GERD) with laryngopharyngeal manifestations. To determine the relationship between laryngeal signs and MII/pH, we examined correlations between Reflux Finding Score (RFS) ratings of videostroboscopic laryngeal examinations and findings from MII/pH. Study Design Correlational study. Methods Healthy, untreated volunteers (n =142) underwent reflux diagnosis using data acquired from MII/pH testing. Eight trained clinicians performed RFS ratings of corresponding laryngeal examinations. Averaged RFS ratings were compared to MII/pH data using Pearson correlation coefficients. The relationship between RFS and MII/pH findings and demographic/clinical information (age, sex, smoking status, reflux) was assessed using general linear modeling. Rater reliability was evaluated. Results Posterior commissure hypertrophy was negatively correlated with minutes of nonacid refluxate (R=-0.21, p=0.0115). General linear modeling revealed that 28-40% of the variance in ratings of ventricular obliteration, erythema/hyperemia, vocal fold edema, diffuse laryngeal edema, posterior commissure hypertrophy, and granulation/granuloma could be explained by main and interaction effects of age, sex, smoking status, and reflux. Intra- and inter-rater reliability for RFS were poor-fair. Conclusion These results support the theory that the RFS is not specific for reflux in healthy, untreated volunteers, suggesting there may be alternate explanations for inflammatory clinical signs commonly ascribed to reflux in this population. PMID:24782404

  13. Magnetic Retraction of Bowel by Intraluminal Injectable Cyanoacrylate-Based Magnetic Glue

    PubMed Central

    Brown, Andrew; André, Pascal; Brown, Stuart I.; Florence, Gordon J.; Cuschieri, Alfred

    2013-01-01

    Magnetic retraction offers advantages over physical retraction by graspers because of reduced tissue trauma. The objectives of this study are to investigate a novel method of magnetisation of bowel segments by intraluminal injection of magnetic glue and to demonstrate the feasibility of magnetic retraction of bowel with sufficient force during minimal access surgery. Following an initial materials characterisation study, selected microparticles of stainless steel (SS410-μPs) were mixed with chosen cyanoacrylate glue (Loctite 4014). During intraluminal injection of the magnetic glue using ex vivo porcine colonic segments, a magnetic probe placed at the injected site ensured that the SS410-μPs aggregated during glue polymerisation to form an intraluminal mucosally adherent coagulum. The magnetised colonic segments were retracted by magnetic probes (5 and 10 mm) placed external to the bowel wall. A tensiometer was used to record the retraction force. With an injected volume of 2 mL in a particle concentration of 1 g/mL, this technique produced maximal magnetic retraction forces of 2.24 ± 0.23 N and 5.11 ± 0.34 N (n = 20), with use of 5 and 10 mm probes, respectively. The results indicate that the formation of an intraluminal coagulum based on SS410-μPs and Loctite 4014 produces sufficient magnetic retraction for bowel retraction. PMID:24319684

  14. Intraluminal brachytherapy in oesophageal cancer: defining its role and introducing the technique

    PubMed Central

    Strnad, Vratislav

    2014-01-01

    Intraluminal brachytherapy plays an important role in the treatment of oesophageal tumours. This article aims to define this role in the curative as well as in the palliative treatment settings drawing on data from the literature, and also emphasizing its potential for harm when used inexpertly. It also provides a short introduction to practical aspects of the treatment procedure and treatment planning. PMID:25097567

  15. Criteria for multiple noises in residential buildings using combined rating system

    NASA Astrophysics Data System (ADS)

    Jeon, Jin Yong; Ryu, Jong Kwan; Jeong, Young

    2005-04-01

    Multiple residential noises such as floor impact, air-borne, bathroom, drainage, and traffic noises were classified using a combined rating system developed from a social noise survey and auditory experiments. The effect of individual noise perception on the evaluation of the overall noise environment was investigated through a questionnaire survey on annoyance, disturbance, and noise sensitivity. In addition, auditory experiments were undertaken to determine the allowable sound pressure level for each residential noise source and the percent satisfaction for individual noise levels. From the results of the survey and the auditory experiments, a combined rating system was developed and annoyance criteria for multiple residential noises were suggested.

  16. Combining versus Analyzing Multiple Causes: How Domain Assumptions and Task Context Affect Integration Rules

    ERIC Educational Resources Information Center

    Waldmann, Michael R.

    2007-01-01

    In everyday life, people typically observe fragments of causal networks. From this knowledge, people infer how novel combinations of causes they may never have observed together might behave. I report on 4 experiments that address the question of how people intuitively integrate multiple causes to predict a continuously varying effect. Most…

  17. Tcoffee@igs: A web server for computing, evaluating and combining multiple sequence alignments.

    PubMed

    Poirot, Olivier; O'Toole, Eamonn; Notredame, Cedric

    2003-07-01

    This paper presents Tcoffee@igs, a new server provided to the community by Hewlet Packard computers and the Centre National de la Recherche Scientifique. This server is a web-based tool dedicated to the computation, the evaluation and the combination of multiple sequence alignments. It uses the latest version of the T-Coffee package. Given a set of unaligned sequences, the server returns an evaluated multiple sequence alignment and the associated phylogenetic tree. This server also makes it possible to evaluate the local reliability of an existing alignment and to combine several alternative multiple alignments into a single new one. Tcoffee@igs can be used for aligning protein, RNA or DNA sequences. Datasets of up to 100 sequences (2000 residues long) can be processed. The server and its documentation are available from: http://igs-server.cnrs-mrs.fr/Tcoffee/.

  18. Video contents summary using the combination of multiple MPEG-7 metadata

    NASA Astrophysics Data System (ADS)

    Lee, Hee Kyung; Kim, Cheon S.; Jung, Yong J.; Nam, Je Ho; Kang, Kyeong O.; Ro, Yong M.

    2002-03-01

    We propose a content-based summary generation method using MPEG-7 metadata. In this paper, the important events of video are defined and subsequently shot boundary detection is carried out. Then, we analyze the video contents in the shot with multiple content features using multiple MPEG-7 descriptors. In experiments with a golf-video, we combined motion activity, edge histogram and homogeneous texture for the detection of event. Further, the extracted segments and key-frames of each event are described by XML document. Experimental result shows that the proposed method gives reliable summary generation with robust event detection.

  19. A new sensitizer DVDMS combined with multiple focused ultrasound treatments: an effective antitumor strategy

    PubMed Central

    Xiong, Wenli; Wang, Pan; Hu, Jianmin; Jia, Yali; Wu, Lijie; Chen, Xiyang; Liu, Quanhong; Wang, Xiaobing

    2015-01-01

    Sonodynamic therapy (SDT) was developed as a promising noninvasive approach. The present study investigated the antitumor effect of a new sensitizer (sinoporphyrin sodium, referred to as DVDMS) combined with multiple ultrasound treatments on sarcoma 180 both in vitro and in vivo. The combined treatment significantly suppressed cell viability, potentiated apoptosis, and markedly inhibited angiogenesis in vivo. In vivo, the tumor weight inhibition ratio reached 89.82% fifteen days after three sonication treatments plus DVDMS. This effect was stronger than one ultrasound alone (32.56%) and than one round of sonication plus DVDMS (59.33%). DVDMS combined with multiple focused ultrasound treatments initiated tumor tissue destruction, induced cancer cell apoptosis, inhibited tumor angiogenesis, suppressed cancer cell proliferation, and decreased VEGF and PCNA expression levels. Moreover, the treatment did not show obvious signs of side effects or induce a drop in body weight. These results indicated that DVDMS combined with multiple focused ultrasounds may be a promising strategy against solid tumor. PMID:26631871

  20. A Combined Neutron and Gamma-Ray Multiplicity Counter Based on Liquid Scintillation Detectors

    SciTech Connect

    Andreas Enqvist; Marek Flaska; Jennifer Dolan; David L. Chichester; Sara A. Pozzi

    2011-10-01

    Multiplicity counters for neutron assay have been extensively used in materials control and accountability for nonproliferation and nuclear safeguards. Typically, neutron coincidence counters are utilized in these fields. In this work, we present a measurement system that makes use not only of neutron (n) multiplicity counting but also of gamma-ray (g) multiplicity counting and the combined higher-order multiples containing both neutrons and gamma rays. The benefit of this approach is in using both particle types available from the sample, leading to a reduction in measurement times needed when using more measurables. We present measurement results of n, g, nn, ng, gg, nnn, nng, ngg, and ggg multiples emitted by Mixed-Oxide (MOX) samples measured at Idaho National Laboratory (INL). The MOX measurement is compared to initial validation of the detection system done using a 252Cf source. The dual radiation measuring system proposed here uses extra measurables to improve the statistics when compared to a neutron-only system and allows for extended analysis and interpretation of sample parameters. New challenges such as the effect of very high intrinsic gamma-ray sources in the case of MOX samples is discussed. Successful measurements of multiples rates can be performed also when using high-Z shielding.

  1. TRACHEOSTOMAPLASTY: A SURGICAL METHOD FOR IMPROVING RETENTION OF AN INTRALUMINAL STOMA BUTTON FOR HANDS-FREE TRACHEOESOPHAGEAL SPEECH

    PubMed Central

    Moreno, Mauricio A.; Lewin, Jan S.; Hutcheson, Katherine A.; Bishop Leone, Julie K.; Barringer, Denise A.

    2014-01-01

    Background We describe a minimally invasive surgical technique, tracheostomaplasty, to overcome anatomical deformities of the stoma that preclude successful retention of a stoma button for hands free tracheoesophageal (TE) speech. Methods We conducted a retrospective analysis of 21 patients who underwent tracheostomaplasty after laryngectomy to accommodate an intraluminal valve attachment for hands-free TE speech. Results Sixteen men and 5 women (median age, 65 years; median follow-up, 27.7 months) underwent tracheostomaplasty; 6 patients developed a mild cellulitis that required therapy and 5 patients required a minor revision surgery. At last follow-up, 15 (71%) patients successfully achieved hands-free TE speech using an intraluminal stoma button. Three patients only retained the intraluminal device to facilitate digital occlusion. Tracheostomaplasty failed in 3 patients because of granulation tissue formation or stomal stenosis. Conclusions Tracheostomaplasty is a successful technique to improve intraluminal retention of a stoma button for hands-free TE speech in laryngectomy patients. PMID:20848405

  2. Acute small bowel obstruction due to a large intraluminal blood clot after laparoscopic Roux-en-Y gastric bypass.

    PubMed

    Green, Jessica; Ikuine, Tomoko; Hacker, Shoshana; Urrego, Hernan; Tuggle, Karleena

    2016-01-01

    Small bowel obstructions (SBOs) are a known perioperative complication of laparoscopic Roux-en-Y gastric bypass and common etiologies include internal hernia, port site hernia, jejunojejunostomy stricture, ileus and adhesions. Less commonly, SBO can be caused by superior mesenteric artery syndrome, intussusception and intraluminal blood clot. We present a case of SBO caused by intraluminal blood clot from jejunojejunostomy staple line bleeding in a patient with a normal coagulation profile. Computed tomography was used to elucidate the cause of perioperative SBO, and diagnostic laparoscopy was used to both diagnose and treat the complication. In this case, the intraluminal clot was evacuated laparoscopically by enterotomy, thrombectomy and primary closure without anastomotic revision since there was no evidence of continued bleeding. Administration of enoxaparin and Toradol post-operatively may have exacerbated mild intraluminal bleeding occurring at the stapled jejunojejunal anastomosis. Prompt recognition and treatment of perioperative SBO can prevent catastrophic consequences related to bowel perforation. PMID:27554828

  3. Acute small bowel obstruction due to a large intraluminal blood clot after laparoscopic Roux-en-Y gastric bypass

    PubMed Central

    Green, Jessica; Ikuine, Tomoko; Hacker, Shoshana; Urrego, Hernan; Tuggle, Karleena

    2016-01-01

    Small bowel obstructions (SBOs) are a known perioperative complication of laparoscopic Roux-en-Y gastric bypass and common etiologies include internal hernia, port site hernia, jejunojejunostomy stricture, ileus and adhesions. Less commonly, SBO can be caused by superior mesenteric artery syndrome, intussusception and intraluminal blood clot. We present a case of SBO caused by intraluminal blood clot from jejunojejunostomy staple line bleeding in a patient with a normal coagulation profile. Computed tomography was used to elucidate the cause of perioperative SBO, and diagnostic laparoscopy was used to both diagnose and treat the complication. In this case, the intraluminal clot was evacuated laparoscopically by enterotomy, thrombectomy and primary closure without anastomotic revision since there was no evidence of continued bleeding. Administration of enoxaparin and Toradol post-operatively may have exacerbated mild intraluminal bleeding occurring at the stapled jejunojejunal anastomosis. Prompt recognition and treatment of perioperative SBO can prevent catastrophic consequences related to bowel perforation. PMID:27554828

  4. Combined spatial diversity and time equalization for broadband multiple channel underwater acoustic communications

    NASA Astrophysics Data System (ADS)

    Skoro Kaskarovska, Violeta

    High data rate acoustic communications become feasible with the use of communication systems that operate at high frequency. The high frequency acoustic transmission in shallow water endures severe distortion as a result of the extensive intersymbol interference and Doppler shift, caused by the time variable multipath nature of the channel. In this research a Single Input Multiple Output (SIMO) acoustic communication system is developed to improve the reliability of the high data rate communications at short range in the shallow water acoustic channel. The proposed SIMO communication system operates at very high frequency and combines spatial diversity and decision feedback equalizer in a multilevel adaptive configuration. The first configuration performs selective combining on the equalized signals from multiple receivers and generates quality feedback parameter for the next level of combining. The second configuration implements a form of turbo equalization to evaluate the individual receivers using the feedback parameters as decision symbols. The improved signals from individual receivers are used in the next iteration of selective combining. Multiple iterations are used to achieve optimal estimate of the received signal. The multilevel adaptive configuration is evaluated on experimental and simulated data using SIMO system with three, four and five receivers. The simulation channel model developed for this research is based on experimental channel and Rician fading channel model. The performance of the channel is evaluated in terms of Bit Error Rate (BER) and Signal-to-Noise-and-Interference Ratio (SNIR). Using experimental data with non-zero BER, multilevel adaptive spatial diversity can achieve BER of 0 % and SNIR gain of 3 dB. The simulation results show that the average BER and SNIR after multilevel combining improve dramatically compared to the single receiver, even in case of extremely high BER of individual received signals. The results demonstrate the

  5. Mechanical characterization of intraluminal tissue with phase-resolved photoacoustic viscoelasticity endoscopy.

    PubMed

    Chen, Conggui; Zhao, Yue; Yang, Sihua; Xing, Da

    2015-12-01

    We developed a phase-sensitive side-scanning photoacoustic viscoelasticity endoscopy (PAVEE) for mechanical characterization of intraluminal tissues. In PAVEE, the PA phase can be extracted from the optical absorption induced ultrasonic waves and provides an index of viscoelasticity that is closely linked to tissue compositions. The transverse resolution of the PAVEE measured by carbon fiber was about 32 μm. The imaging capability of the PAVEE was verified using a vessel-mimicking phantom with different agar density. Moreover, PAVEE was investigated in processed lumen-shaped vascular tissues to evaluate the biomechanical features, which was highly consistent with the histology. The results demonstrated that the PAVEE can obtain viscoelastic properties of intraluminal tissues, which puts a new insight into the intravascular disease and holds great promise for plaque vulnerability detection. PMID:26713209

  6. Atorvastatin calcium in combination with methylprednisolone for the treatment of multiple sclerosis relapse.

    PubMed

    Li, Xiao-ling; Zhang, Zhen-chang; Zhang, Bo; Jiang, Hua; Yu, Chun-mei; Zhang, Wen-jing; Yan, Xiang; Wang, Man-xia

    2014-12-01

    This study aimed to investigate the efficacy of combined atorvastatin calcium and methylprednisolone for the treatment of multiple sclerosis relapse. Patients with multiple sclerosis (MS) at the relapse phase were randomized to receive either combined treatment of atorvastatin calcium and methylprednisolone (n = 19) or methylprednisolone alone (n = 19). Expanded Disability Status Scale (EDSS) was administered at baseline, 1 week, 2 weeks, 4 weeks, 3 months, and 6 months after treatment initiation. The number and volume of brain lesions were evaluated using magnetic resonance imaging at baseline and 6 months. The levels of IL-13, IL-35, IFN-γ, and IL-10 in the cerebrospinal fluid were examined using the enzyme-linked immunosorbent assay method. There was no significant difference in EDSS scores at 1, 2, and 4 weeks. At 3 and 6 months, the combined treatment group showed significantly lower EDSS scores than the monotherapy group (P < 0.05). The number and volume of brain lesions in the combined treatment group were significantly lower than the monotherapy group at 6 months (P < 0.001). The mean time to relapse was significantly extended in the combined treatment group than the monotherapy group (P < 0.001). At 2 and 4 weeks, the combined treatment group had significantly higher levels of IL-13, IL-35, and IL-10 in the cerebrospinal fluid than the monotherapy group (P < 0.05), but significantly lower level of IFN-γ (P < 0.001). The levels of IL-13 and IL-10 in the combined treatment group were positively correlated with EDSS scores (r = 0.632, P = 0.001; r = 0.731, P = 0.002). Combined treatment with atorvastatin calcium and methylprednisolone can improve the outcomes of MS relapse compared with glucocorticosteroid alone.

  7. Two Cases of Intraluminal “Windsock” Diverticula Resulting in Partial Duodenal Obstruction

    PubMed Central

    Provost, Justin; Bakr, Maged; Bach, Christopher; Merchant, Prakriti; Brown, Christopher; Gruss, Claudia

    2016-01-01

    An intraluminal duodenal diverticulum (IDD) is a rare congenital anomaly that is the result of incomplete recanalization of the embryologic foregut leaving a fenestrated membrane within the lumen of the duodenum. Years of peristalsis acting on the membrane result in the formation of a diverticulum. Most patients are asymptomatic, while some may have abdominal pain, bloating, or fullness. Rare complications include gastrointestinal bleeding, obstruction, pancreatitis, and cholangitis. We present 2 cases with endoscopic findings consistent with partially obstructing symptomatic IDD. PMID:27807587

  8. Combining multiple healthcare databases for postmarketing drug and vaccine safety surveillance: why and how?

    PubMed

    Trifirò, G; Coloma, P M; Rijnbeek, P R; Romio, S; Mosseveld, B; Weibel, D; Bonhoeffer, J; Schuemie, M; van der Lei, J; Sturkenboom, M

    2014-06-01

    A growing number of international initiatives (e.g. EU-ADR, Sentinel, OMOP, PROTECT and VAESCO) are based on the combined use of multiple healthcare databases for the conduct of active surveillance studies in the area of drug and vaccine safety. The motivation behind combining multiple healthcare databases is the earlier detection and validation, and hence earlier management, of potential safety issues. Overall, the combination of multiple healthcare databases increases statistical sample size and heterogeneity of exposure for postmarketing drug and vaccine safety surveillance, despite posing several technical challenges. Healthcare databases generally differ by underlying healthcare systems, type of information collected, drug/vaccine and medical event coding systems and language. Therefore, harmonization of medical data extraction through homogeneous coding algorithms across highly different databases is necessary. Although no standard procedure is currently available to achieve this, several approaches have been developed in recent projects. Another main challenge involves choosing the work models for data management and analyses whilst respecting country-specific regulations in terms of data privacy and anonymization. Dedicated software (e.g. Jerboa) has been produced to deal with privacy issues by sharing only anonymized and aggregated data using a common data model. Finally, storage and safe access to the data from different databases requires the development of a proper remote research environment. The aim of this review is to provide a summary of the potential, disadvantages, methodological issues and possible solutions concerning the conduct of postmarketing multidatabase drug and vaccine safety studies, as demonstrated by several international initiatives.

  9. Virtual intraluminal evaluation of aortico-left ventricular tunnel by multislice computed tomography.

    PubMed

    Hsu, Jong-Hau; Wu, Ding-Kwo; Chen, Ying-Fu; Dai, Zen-Kong; Lee, Meng-Hsun; Wu, Jiunn-Ren

    2007-03-20

    The aortico-left ventricular tunnel (ALVT) is a rare abnormal channel that arises from the right coronary sinus through the right ventricular outflow tract to enter the left ventricle below the aortic valve. The unique ability of multislice computed tomography (CT), as applied in the virtual coloscopy, has not been well established in patients with cardiovascular diseases. We herein investigate the virtual intraluminal image in a patient with an ALVT. An 18-year-old male was admitted with a 6-month-long history of progressive exertional dyspnea. He was diagnosed to suffer from ALVT at 5 months of age and received prosthetic patch closure of the aortic opening of the tunnel with mild residual aortic regurgitation. On admission this time, physical examination revealed a grade 3/6 diastolic murmur over the right upper sternal border. A 16-row multislice CT angiography demonstrated an ALVT. In the 3D reconstructed images, the orifice and intraluminal structure of ALVT were clearly visualized at different levels, similar to a real intracardiac endoscopic images. The patient was then referred for aortic valve replacement due to heart failure caused by severe degenerative aortic insufficiency. Our case displayed successfully not only the entire location of ALVT but also demonstrated the virtual intraluminal imaging mimicking endoscopy. This technique provides the virtual visualization of the entire inner image of AVLT, which may not be possible with other imaging modalities.

  10. Surgical correction of aortic disease using intraluminal, crimped bovine pericardial graft.

    PubMed

    Bernardes, R de C; Reis Filho, F A; Marino, R L; Marino, M A; de Castro, A C; Rabelo, W; Rabelo, R C

    1995-08-01

    We propose the use of a crimped bovine pericardial graft joined to a rigid and grooved ring for the treatment of aortic dissections and aneurysms. This device was developed to support common tubular vascular prostheses of any material, length, diameter, or form, transforming them into intraluminal ones during the surgical procedure. During March 1989 to May 1994, 74 patients underwent an operation on the aorta in which this intraluminal ring, prepared from a tubular prosthesis of bovine pericardium, was used. Twenty-seven patients had an acute type A aortic dissection, 6 had an acute type B aortic dissection, 10 had annuloaortic ectasia, 6 had a descending aortic aneurysm, 3 had a thoracoabdominal aneurysm, and 22 had an abdominal aneurysm. The global mortality rate of 10.8% in the immediate postoperative period cannot be related to the surgical technique or the type of prosthesis used. We conclude from our findings that this modification of the sutureless intraluminal graft, which allows it to be used to replace diseased segments of the aorta, affords the quickest and simplest means of repair and is attended by the least likelihood of anastomotic complications.

  11. A new method to combine 3D reconstruction volumes for multiple parallel circular cone beam orbits

    PubMed Central

    Baek, Jongduk; Pelc, Norbert J.

    2010-01-01

    Purpose: This article presents a new reconstruction method for 3D imaging using a multiple 360° circular orbit cone beam CT system, specifically a way to combine 3D volumes reconstructed with each orbit. The main goal is to improve the noise performance in the combined image while avoiding cone beam artifacts. Methods: The cone beam projection data of each orbit are reconstructed using the FDK algorithm. When at least a portion of the total volume can be reconstructed by more than one source, the proposed combination method combines these overlap regions using weighted averaging in frequency space. The local exactness and the noise performance of the combination method were tested with computer simulations of a Defrise phantom, a FORBILD head phantom, and uniform noise in the raw data. Results: A noiseless simulation showed that the local exactness of the reconstructed volume from the source with the smallest tilt angle was preserved in the combined image. A noise simulation demonstrated that the combination method improved the noise performance compared to a single orbit reconstruction. Conclusions: In CT systems which have overlap volumes that can be reconstructed with data from more than one orbit and in which the spatial frequency content of each reconstruction can be calculated, the proposed method offers improved noise performance while keeping the local exactness of data from the source with the smallest tilt angle. PMID:21089770

  12. Wireless 'mini' multichannel intraluminal impedance-pH: what is the optimal design of a miniature wireless device?

    PubMed

    Heard, R; Sharma, N; Roberts, J; Castell, D; Pohl, D

    2014-07-01

    Catheter-based methods for multichannel intraluminal impedance-pH monitoring are invasive and uncomfortable. The current alternative is a wireless system that clips to the esophageal mucosa, but which only measures pH. A shorter two-site wireless sensor that detects impedance and pH, and can be clipped to the esophagus, would be desirable. This study compares sensor positions and separations to determine the optimal configuration of a two-site wireless sensor. Records of 20 patients (10 on and 10 off proton pump inhibitor) who had ambulatory reflux testing with a multichannel intraluminal impedance-pH system (Sandhill Scientific Inc., Highlands Ranch, CO, USA) with six impedance and two pH sensors were reviewed. An investigator was blinded to four combinations of impedance channels plus pH. He read a 3-hour postprandial section from each of the combinations (total of 80 studies) and marked reflux episodes. Results were compared with his own interpretation of the full tracing. Two hundred and two total reflux episodes were analyzed, 113 acid (pH < 4) and 89 nonacid (pH > 4). Mean and median numbers of total reflux episodes were calculated. In the full study, the interpreter detected a mean of 10 reflux episodes per study. In the 5 cm and 7 cm, 3 cm and 7 cm, and 3 cm and 5 cm studies, the interpreter found a mean of 8.1, 11.1, and 9.8 reflux episodes per study, respectively. One-way analysis of variance yielded a P-value of 0.43. The trend of these preliminary findings suggests that the 3 cm and 5 cm site is the most sensitive and the 5 cm and 7 cm is the least, with the 3 cm and 7 cm site perhaps as the preferred location. The lack of a significant difference, at the very least, suggests that any of the 'mini' locations could be used. The small number of observations could have resulted in a Type II statistical error.

  13. The SI-Combiner: Making sense of results from multiple trained programs

    SciTech Connect

    Den Hartog, B.K.; Elling, J.W.; Kieckhafer, R.

    1998-12-31

    Many problems, such as Aroclor Interpretation, are ill-conditioned problems in which trained programs, or methods, must operate in scenarios outside their training ranges because it is intractable to train them completely. Consequently, they fail in ways related to the scenarios. Importantly, when multiple trained methods fail divergently, their patterns of failures provide insights into the true results. The SI-Combiner solves this problem of Integrating Multiple learned Models (IMLM) by automatically learning and using these insights to produce a solution more accurate than any single trained program. In application, the Aroclor Interpretation SI-Combiner improved on the accuracy of the most accurate individual trained program in the suite. This paper presents a new fuzzy IMLM method called the SI-Combiner and its application to Aroclor Interpretation. Additionally, this paper shows the improvement in accuracy that the SI-Combiner`s components show against Multicategory Classification (MCC), Dempster-Shafer (DS), and the best individual trained program in the Aroclor Interpretation suite (iMLR).

  14. Combining complementary multiple bandgaps in one-dimensional plasma photonic crystal heterostructures

    NASA Astrophysics Data System (ADS)

    Zhang, Juan; Zou, Junhui; Wang, Yang

    2016-10-01

    A single bandgap overlapping scheme is often used to enlarge the photonic bandgap (PBG) range in cascaded or hetero one-dimensional photonic crystal (1D PC) structures. In this paper, we design an optimized one-dimensional plasma photonic crystal (1D PPC) heterostructure based on the idea of combining complementary multiple PBGs to enlarge the PBG range. The flexibility of the PBG of a 1D PPC, caused by the frequency-dependent dispersive properties of plasma, is helpful for generating and combining multiple bandgaps. The obtained omni-directional photonic bandgap (ODPBG) width for the 1D PPC heterostructure is dramatically enhanced compared with that of a single 1D PPC alone and is much larger than that of 1D PC heterostructures described in the previous works. Further study shows that the PPC heterostructures are more suitable than other heterostructures (such as a 1D PC heterostructure or heterostructures composed of a 1D PPC and 1D PC) for combining complementary PBGs. The ODPBG ranges for 1D PPC heterostructures can be further extended by adjusting the parameters of the plasma to allow more complementary PBGs to combine with each other.

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Combination of cyclophosphamide and interferon-β halts progression in patients with rapidly transitional multiple sclerosis

    PubMed Central

    Patti, F; Cataldi, M; Nicoletti, F; Reggio, E; Nicoletti, A; Reggio, A

    2001-01-01

    The effects of combined treatment with cyclophosphamide (CTX) and interferon-β (IFN-β) are described in selected patients with "rapidly transitional" multiple sclerosis. This form of multiple sclerosis is extremely active with very frequent and severe attacks which produce a dramatic increase on the expanded disability status scale (EDSS). Ten patients with rapidly transitional multiple sclerosis were previously treated with interferon-β, but none benefited by this treatment. Monthly treatment with intravenous CTX, from 500 mg/m2 to 1500 mg/m2 to obtain a chronic lymphocytopenia (600/mm3 to 900/mm3) produced a marked and significant reduction in the number of relapses (p<0.0001), disability previously accumulated (p<0.0001), and a reduction of T2 MRI burden of lesion. This particular group of patients benefited by combining cyclophosphamide and IFN-β. The possibility is considered of carrying out further studies to test the efficacy of the association between the two drugs for patients who are not responsive to IFN-β or other active disease modifying therapies.

 PMID:11511721

  17. Mixed-point geostatistical simulation: A combination of two- and multiple-point geostatistics

    NASA Astrophysics Data System (ADS)

    Cordua, Knud Skou; Hansen, Thomas Mejer; Gulbrandsen, Mats Lundh; Barnes, Christophe; Mosegaard, Klaus

    2016-09-01

    Multiple-point-based geostatistical methods are used to model complex geological structures. However, a training image containing the characteristic patterns of the Earth model has to be provided. If no training image is available, two-point (i.e., covariance-based) geostatistical methods are typically applied instead because these methods provide fewer constraints on the Earth model. This study is motivated by the case where 1-D vertical training images are available through borehole logs, whereas little or no information about horizontal dependencies exists. This problem is solved by developing theory that makes it possible to combine information from multiple- and two-point geostatistics for different directions, leading to a mixed-point geostatistical model. An example of combining information from the multiple-point-based single normal equation simulation algorithm and two-point-based sequential indicator simulation algorithm is provided. The mixed-point geostatistical model is used for conditional sequential simulation based on vertical training images from five borehole logs and a range parameter describing the horizontal dependencies.

  18. Multiple scales combined principle component analysis deep learning network for face recognition

    NASA Astrophysics Data System (ADS)

    Tian, Lei; Fan, Chunxiao; Ming, Yue

    2016-03-01

    It is well known that higher level features can represent the abstract semantics of original data. We propose a multiple scales combined deep learning network to learn a set of high-level feature representations through each stage of convolutional neural network for face recognition, which is named as multiscaled principle component analysis (PCA) Network (MS-PCANet). There are two main differences between our model and the traditional deep learning network. On the one hand, we get the prefixed filter kernels by learning the principal component of images' patches using PCA, nonlinearly process the convolutional results by using simple binary hashing, and pool them using spatial pyramid pooling method. On the other hand, in our model, the output features of several stages are fed to the classifier. The purpose of combining feature representations from multiple stages is to provide multiscaled features to the classifier, since the features in the latter stage are more global and invariant than those in the early stage. Therefore, our MS-PCANet feature compactly encodes both holistic abstract information and local specific information. Extensive experimental results show our MS-PCANet model can efficiently extract high-level feature presentations and outperform state-of-the-art face/expression recognition methods on multiple modalities benchmark face-related datasets.

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

    PubMed Central

    Grenley, Marc O.; Casalini, Joseph R.; Tretyak, Ilona; Ditzler, Sally H.; Thirstrup, Derek J.; Frazier, Jason P.; Pierce, Daniel W.; Carleton, Michael; Klinghoffer, Richard A.

    2016-01-01

    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. PMID:27359113

  20. Genetic polymorphisms, their allele combinations and IFN-β treatment response in Irish multiple sclerosis patients

    PubMed Central

    O’Doherty, Catherine; Favorov, Alexander; Heggarty, Shirley; Graham, Colin; Favorova, Olga; Ochs, Michael; Hawkins, Stanley; Hutchinson, Michael; O’Rourke, Killian; Vandenbroeck, Koen

    2009-01-01

    Introduction IFN-β is widely used as first-line immunomodulatory treatment for multiple sclerosis. Response to treatment is variable (30–50% of patients are nonresponders) and requires a long treatment duration for accurate assessment to be possible. Information about genetic variations that predict responsiveness would allow appropriate treatment selection early after diagnosis, improve patient care, with time saving consequences and more efficient use of resources. Materials & methods We analyzed 61 SNPs in 34 candidate genes as possible determinants of IFN-β response in Irish multiple sclerosis patients. Particular emphasis was placed on the exploration of combinations of allelic variants associated with response to therapy by means of a Markov chain Monte Carlo-based approach (APSampler). Results The most significant allelic combinations, which differed in frequency between responders and nonresponders, included JAK2–IL10RB–GBP1–PIAS1 (permutation p-value was pperm = 0.0008), followed by JAK2–IL10–CASP3 (pperm = 0.001). Discussion The genetic mechanism of response to IFN-β is complex and as yet poorly understood. Data mining algorithms may help in uncovering hidden allele combinations involved in drug response versus nonresponse. PMID:19604093

  1. An Adaptive Fisher’s Combination Method for Joint Analysis of Multiple Phenotypes in Association Studies

    PubMed Central

    Liang, Xiaoyu; Wang, Zhenchuan; Sha, Qiuying; Zhang, Shuanglin

    2016-01-01

    Currently, the analyses of most genome-wide association studies (GWAS) have been performed on a single phenotype. There is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases. Therefore, using only one single phenotype may lose statistical power to identify the underlying genetic mechanism. There is an increasing need to develop and apply powerful statistical tests to detect association between multiple phenotypes and a genetic variant. In this paper, we develop an Adaptive Fisher’s Combination (AFC) method for joint analysis of multiple phenotypes in association studies. The AFC method combines p-values obtained in standard univariate GWAS by using the optimal number of p-values which is determined by the data. We perform extensive simulations to evaluate the performance of the AFC method and compare the power of our method with the powers of TATES, Tippett’s method, Fisher’s combination test, MANOVA, MultiPhen, and SUMSCORE. Our simulation studies show that the proposed method has correct type I error rates and is either the most powerful test or comparable with the most powerful test. Finally, we illustrate our proposed methodology by analyzing whole-genome genotyping data from a lung function study. PMID:27694844

  2. Bayesian model selection for multiple QTLs mapping combining linkage disequilibrium and linkage.

    PubMed

    Jiang, Dan; Ma, Guoda; Yang, Runqing; Li, Keshen; Fang, Ming

    2014-01-01

    Linkage disequilibrium (LD) mapping is able to localize quantitative trait loci (QTL) within a rather small region (e.g. 2 cM), which is much narrower than linkage analysis (LA, usually 20 cM). The multilocus LD method utilizes haplotype information around putative mutation and takes historical recombination events into account, and thus provides a powerful method for further fine mapping. However, sometimes there are more than one QTLs in the region being studied. In this study, the Bayesian model selection implemented via the Markov chain Monte Carlo (MCMC) method is developed for fine mapping of multiple QTLs using haplotype information in a small region. The method combines LD as well as linkage information. A series of simulation experiments were conducted to investigate the behavior of the method. The results showed that this new multiple QTLs method was more efficient in separating closely linked QTLs than single-marker association studies. PMID:25579473

  3. Bayesian model selection for multiple QTLs mapping combining linkage disequilibrium and linkage.

    PubMed

    Jiang, Dan; Ma, Guoda; Yang, Runqing; Li, Keshen; Fang, Ming

    2014-09-19

    Linkage disequilibrium (LD) mapping is able to localize quantitative trait loci (QTL) within a rather small region (e.g. 2 cM), which is much narrower than linkage analysis (LA, usually 20 cM). The multilocus LD method utilizes haplotype information around putative mutation and takes historical recombination events into account, and thus provides a powerful method for further fine mapping. However, sometimes there are more than one QTLs in the region being studied. In this study, the Bayesian model selection implemented via the Markov chain Monte Carlo (MCMC) method is developed for fine mapping of multiple QTLs using haplotype information in a small region. The method combines LD as well as linkage information. A series of simulation experiments were conducted to investigate the behavior of the method. The results showed that this new multiple QTLs method was more efficient in separating closely linked QTLs than single-marker association studies.

  4. High-quality conforming hexahedral meshes of patient-specific abdominal aortic aneurysms including their intraluminal thrombi.

    PubMed

    Tarjuelo-Gutierrez, J; Rodriguez-Vila, B; Pierce, D M; Fastl, T E; Verbrugghe, P; Fourneau, I; Maleux, G; Herijgers, P; Holzapfel, G A; Gomez, E J

    2014-02-01

    In order to perform finite element (FE) analyses of patient-specific abdominal aortic aneurysms, geometries derived from medical images must be meshed with suitable elements. We propose a semi-automatic method for generating conforming hexahedral meshes directly from contours segmented from medical images. Magnetic resonance images are generated using a protocol developed to give the abdominal aorta high contrast against the surrounding soft tissue. These data allow us to distinguish between the different structures of interest. We build novel quadrilateral meshes for each surface of the sectioned geometry and generate conforming hexahedral meshes by combining the quadrilateral meshes. The three-layered morphology of both the arterial wall and thrombus is incorporated using parameters determined from experiments. We demonstrate the quality of our patient-specific meshes using the element Scaled Jacobian. The method efficiently generates high-quality elements suitable for FE analysis, even in the bifurcation region of the aorta into the iliac arteries. For example, hexahedral meshes of up to 125,000 elements are generated in less than 130 s, with 94.8 % of elements well suited for FE analysis. We provide novel input for simulations by independently meshing both the arterial wall and intraluminal thrombus of the aneurysm, and their respective layered morphologies.

  5. Valid flow combinations for stable sheath in a magnetized multiple ion species plasma

    SciTech Connect

    Sharma, Devendra; Kaw, Predhiman K.

    2012-11-15

    Theoretical study is done of the entry criterion for the plasma flow into the electrostatic boundary layer, or sheath, forming in a magnetized multiple ion species plasma. Finding valid entry velocity combinations in a magnetized set up requires a magnetized equivalent of the generalized Bohm criterion. A magnetized generalized entry criterion is obtained with the scale length distribution in a region of validity for the stable solutions. The analysis finds that the valid entry flow velocity combinations with distinct values of individual ion species can correspond to a unique system phase velocity. Magnetization effects govern the region of validity whose boundaries collapse to the unmagnetized sheath criterion in the limit of normal incidence, independent of the strength of the magnetic field. Considerably smaller entry velocities, in comparison to the unmagnetized system sound velocity, are recovered for the species in appropriate regime of magnetization in the cases of oblique incidences.

  6. Confidence intervals after multiple imputation: combining profile likelihood information from logistic regressions.

    PubMed

    Heinze, Georg; Ploner, Meinhard; Beyea, Jan

    2013-12-20

    In the logistic regression analysis of a small-sized, case-control study on Alzheimer's disease, some of the risk factors exhibited missing values, motivating the use of multiple imputation. Usually, Rubin's rules (RR) for combining point estimates and variances would then be used to estimate (symmetric) confidence intervals (CIs), on the assumption that the regression coefficients were distributed normally. Yet, rarely is this assumption tested, with or without transformation. In analyses of small, sparse, or nearly separated data sets, such symmetric CI may not be reliable. Thus, RR alternatives have been considered, for example, Bayesian sampling methods, but not yet those that combine profile likelihoods, particularly penalized profile likelihoods, which can remove first order biases and guarantee convergence of parameter estimation. To fill the gap, we consider the combination of penalized likelihood profiles (CLIP) by expressing them as posterior cumulative distribution functions (CDFs) obtained via a chi-squared approximation to the penalized likelihood ratio statistic. CDFs from multiple imputations can then easily be averaged into a combined CDF c , allowing confidence limits for a parameter β  at level 1 - α to be identified as those β* and β** that satisfy CDF c (β*) = α ∕ 2 and CDF c (β**) = 1 - α ∕ 2. We demonstrate that the CLIP method outperforms RR in analyzing both simulated data and data from our motivating example. CLIP can also be useful as a confirmatory tool, should it show that the simpler RR are adequate for extended analysis. We also compare the performance of CLIP to Bayesian sampling methods using Markov chain Monte Carlo. CLIP is available in the R package logistf. PMID:23873477

  7. Differentiating between heat pain intensities: the combined effect of multiple autonomic parameters.

    PubMed

    Treister, Roi; Kliger, Mark; Zuckerman, Galit; Goor Aryeh, Itay; Eisenberg, Elon

    2012-09-01

    Although it is well known that pain induces changes in autonomic parameters, the extent to which these changes correlate with the experience of pain is under debate. The aim of the present study was to compare a combination of multiple autonomic parameters and each parameter alone in their ability to differentiate among 4 categories of pain intensity. Tonic heat stimuli (1minute) were individually adjusted to induce no pain, low, medium, and high pain in 45 healthy volunteers. Electrocardiogram, photoplethysmogram, and galvanic skin response were recorded, and the following parameters were calculated: heart rate; heart rate variability-high frequency (0.15 to 0.4Hz) spectral power; skin conductance level; number of skin conduction fluctuations; and photoplethysmographic pulse wave amplitude. A combination of parameters was created by fitting an ordinal cumulative logit model to the data and using linear coefficients of the model. Friedman test with post-hoc Wilcoxon test were used to compare between pain intensity categories for every parameter alone and for their linear combination. All of the parameters successfully differentiated between no pain and all other pain categories. However, none of the parameters differentiated between all 3 pain categories (i.e., low and medium; medium and high; low and high). In contrast, the linear combination of parameters significantly differentiated not only between pain and no pain, but also between all pain categories (P<.001 to .02). These results suggest that multiparameter approaches should be further investigated to make progress toward reliable autonomic-based pain assessment.

  8. Construction of a gene-gene interaction network with a combined score across multiple approaches.

    PubMed

    Zhang, A M; Song, H; Shen, Y H; Liu, Y

    2015-01-01

    Recent progress in computational methods for inves-tigating physical and functional gene interactions has provided new insights into the complexity of biological processes. An essential part of these methods is presented visually in the form of gene interaction networks that can be valuable in exploring the mechanisms of disease. Here, a combined network based on gene pairs with an extra layer of re-liability was constructed after converting and combining the gene pair scores using a novel algorithm across multiple approaches. Four groups of kidney cancer data sets from ArrayExpress were downloaded and analyzed to identify differentially expressed genes using a rank prod-ucts analysis tool. Gene co-expression network, protein-protein interac-tion, co-occurrence network and a combined network were constructed using empirical Bayesian meta-analysis approach, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, an odds ratio formula of the cBioPortal for Cancer Genomics and a novel rank algorithm with combined score, respectively. The topological features of these networks were then compared to evaluate their performances. The results indicated that the gene pairs and their relationship rank-ings were not uniform. The values of topological parameters, such as clustering coefficient and the fitting coefficient R(2) of interaction net-work constructed using our ranked based combination score, were much greater than the other networks. The combined network had a classic small world property which transferred information quickly and displayed great resilience to the dysfunction of low-degree hubs with high-clustering and short average path length. It also followed distinct-ly a scale-free network with a higher reliability. PMID:26125911

  9. Combining morphometric evidence from multiple registration methods using dempster-shafer theory

    NASA Astrophysics Data System (ADS)

    Rajagopalan, Vidya; Wyatt, Christopher

    2010-03-01

    In tensor-based morphometry (TBM) group-wise differences in brain structure are measured using high degreeof- freedom registration and some form of statistical test. However, it is known that TBM results are sensitive to both the registration method and statistical test used. Given the lack of an objective model of group variation is it difficult to determine a best registration method for TBM. The use of statistical tests is also problematic given the corrections required for multiple testing and the notorius difficulty selecting and intepreting signigance values. This paper presents an approach to address both of these issues by combining multiple registration methods using Dempster-Shafer Evidence theory to produce belief maps of categorical changes between groups. This approach is applied to the comparison brain morphometry in aging, a typical application of TBM, using the determinant of the Jacobian as a measure of volume change. We show that the Dempster-Shafer combination produces a unique and easy to interpret belief map of regional changes between and within groups without the complications associated with hypothesis testing.

  10. Combining information from multiple flood projections in a hierarchical Bayesian framework

    NASA Astrophysics Data System (ADS)

    Le Vine, Nataliya

    2016-04-01

    This study demonstrates, in the context of flood frequency analysis, the potential of a recently proposed hierarchical Bayesian approach to combine information from multiple models. The approach explicitly accommodates shared multimodel discrepancy as well as the probabilistic nature of the flood estimates, and treats the available models as a sample from a hypothetical complete (but unobserved) set of models. The methodology is applied to flood estimates from multiple hydrological projections (the Future Flows Hydrology data set) for 135 catchments in the UK. The advantages of the approach are shown to be: (1) to ensure adequate "baseline" with which to compare future changes; (2) to reduce flood estimate uncertainty; (3) to maximize use of statistical information in circumstances where multiple weak predictions individually lack power, but collectively provide meaningful information; (4) to diminish the importance of model consistency when model biases are large; and (5) to explicitly consider the influence of the (model performance) stationarity assumption. Moreover, the analysis indicates that reducing shared model discrepancy is the key to further reduction of uncertainty in the flood frequency analysis. The findings are of value regarding how conclusions about changing exposure to flooding are drawn, and to flood frequency change attribution studies.

  11. Measurement of Peak Esophageal Luminal Cross Sectional Area Utilizing Nadir Intraluminal Impedance

    PubMed Central

    Zifan, Ali; Ledgerwood-Lee, Melissa; Mittal, Ravinder K

    2015-01-01

    BACKGROUND Multichannel intraluminal impedance (MII) is currently used to monitor gastroesophageal reflux and esophageal bolus clearance. We describe a novel methodology to measure maximal luminal CSA during bolus transport from MII measurements. METHODS Studies were conducted in-vitro (test tubes) and in-vivo (healthy subjects). Concurrent MII, HRM, and intraluminal ultrasound (US) were recorded 7 cm above the lower esophageal sphincter. Swallows with two concentrations of saline, 0.1N and 0.5N, of bolus volumes 5cc, 10cc and 15cc were performed. The CSA was estimated by solving two algebraic Ohm’s law equations, resulting from the two saline solutions. The CSA calculated from impedance method was compared with the CSA measured from the intraluminal US images. KEY RESULTS The CSA measured in duplicate from B-mode US images showed a mean difference between the two manual delineations to be near zero, and the repeatability coefficient was within 7.7% of the mean of the two CSA measurements. The calculated CSA from the impedance measurements strongly correlated with the US measured CSA (R2 ≅ 0.98). A detailed statistical analysis of the impedance and US measured CSA data indicated that the 95% limits of agreement between the two methods ranged from −9.1 to 13mm2. The root mean square error (RMS) of the two measurements was 4.8% of the mean US-measured CSA. CONCLUSIONS We describe a novel methodology to measure peak esophageal luminal CSA during peristalsis. Further studies are needed to determine if it is possible to measure patterns of luminal distension during peristalsis across the entire length of the esophagus. PMID:25930157

  12. Intraluminal Radioactive Stent Compared with Covered Stent Alone for the Treatment of Malignant Esophageal Stricture

    SciTech Connect

    Wang Zhongmin; Huang Xunbo; Cao Jun; Huang Gang; Chen Kemin LIu Yu; Liu Fenju

    2012-04-15

    Objective: This study was designed to compare the clinical effectiveness of intraluminal radioactive stent loaded with iodine-125 seeds implantation versus covered stent alone insertion in patients with malignant esophageal stricture. Methods: We studied two groups of patients with malignant esophageal stricture. Group A comprised 28 patients (19 men and 9 women) who underwent intraluminal radioactive stent loaded with iodine-125 seeds implantation and were followed prospectively. Group B comprised 30 patients (18 men and 12 women) who had previously received covered stent alone insertion; these patients were evaluated retrospectively. There was no crossover between the two groups during follow-up. Informed consent was obtained from each patient, and our institutional review board approved the study. The dysphagia score, overall survival rates, complication rates, and reintervention rates were compared in the two groups. Results: There were no significant differences between the two groups in terms of baseline characteristics. Stent placement was technically successful and well tolerated in all patients. The dysphagia score was improved in both groups after stent placement. The median survival was significantly longer in group A than in group B: 11 versus 4.9 months, respectively (P < 0.001). The complications of chest pain, esophageal reflux, and stent migration was more frequent in group B, but this difference did not reach statistical significance. There was no statistical difference in reintervention between two groups. Conclusions: Intraluminal radioactive stent loaded with iodine-125 seeds implantation was a feasible and practical management in treating malignant esophageal stricture and was superior to covered stent alone insertion, as measured by survival.

  13. Effects of Intraluminal Irradiation with Holmium-166 for TIPS Stenosis: Experimental Study in a Swine Model

    PubMed Central

    Park, Ji Seon; Kim, Deog Yoon; Park, Yong Koo; Park, Sang Joon; Kim, Soo Joong

    2007-01-01

    Objective We wanted to evaluate the effectiveness of intraluminal irradiation with Holmium-166 (166Ho) for reducing the pseudointimal hyperplasia (PIH) in the transjugular intrahepatic portosystemic shunt (TIPS) tract in a swine model. Materials and Methods TIPS was performed in 12 domestic pigs, after the creation of portal hypertension by intraportal injection of a mixture of N-butyl-2-cyanoacrylate (NBCA) and lipiodol. Five pigs first underwent intraluminal irradiation (30 Gy) in the parenchymal tract with using a 166Ho solution-filled balloon catheter, and this was followed by the placement of a nitinol stent in the TIPS tract. For the seven control pigs, the balloon was filled with saline and contrast media mixture. Two weeks later, follow-up portography and histological analysis were performed. Results TIPS was successfully performed in all twelve pigs with achieving artificially induced portal hypertension. Portography performed two weeks after TIPS showed the patent tracts in the TIPS tracts that were irradiated with 166Ho (5/5, 100%), whereas either completely (5/6, 83.3%) or partially (1/6, 16.7%) occluded TIPS were seen in the seven pigs of the nonirradiated control group, except in one pig that experienced periprocedural death due to bleeding. Histological analysis showed a statistically significant difference for the maximal PIH (irradiated: 32.8%, nonirradiated: 76.0%, p < 0.001) between the two groups. Conclusion Intraluminal irradiation with 30 Gy of 166Ho for TIPS significantly improved the TIPS patency in a swine model of portal hypertension during a 2-week period of follow-up. PMID:17420630

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

    PubMed

    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

  15. Combining multiple imputation and meta-analysis with individual participant data.

    PubMed

    Burgess, Stephen; White, Ian R; Resche-Rigon, Matthieu; Wood, Angela M

    2013-11-20

    Multiple imputation is a strategy for the analysis of incomplete data such that the impact of the missingness on the power and bias of estimates is mitigated. When data from multiple studies are collated, we can propose both within-study and multilevel imputation models to impute missing data on covariates. It is not clear how to choose between imputation models or how to combine imputation and inverse-variance weighted meta-analysis methods. This is especially important as often different studies measure data on different variables, meaning that we may need to impute data on a variable which is systematically missing in a particular study. In this paper, we consider a simulation analysis of sporadically missing data in a single covariate with a linear analysis model and discuss how the results would be applicable to the case of systematically missing data. We find in this context that ensuring the congeniality of the imputation and analysis models is important to give correct standard errors and confidence intervals. For example, if the analysis model allows between-study heterogeneity of a parameter, then we should incorporate this heterogeneity into the imputation model to maintain the congeniality of the two models. In an inverse-variance weighted meta-analysis, we should impute missing data and apply Rubin's rules at the study level prior to meta-analysis, rather than meta-analyzing each of the multiple imputations and then combining the meta-analysis estimates using Rubin's rules. We illustrate the results using data from the Emerging Risk Factors Collaboration. PMID:23703895

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

    PubMed

    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

  17. Intraluminal Bowel Erosion: A Rare Complication of Retained Gallstones after Cholecystectomy

    PubMed Central

    McQuay, Nathaniel

    2016-01-01

    Laparoscopic cholecystectomy for acute cholecystitis and cholelithiasis is one of the most common operations performed in the United States. Inadvertent perforation and spillage of gallbladder contents are not uncommon. The potential impact of subsequent retained gallstones is understated. We present the case of an intraperitoneal gallstone retained from a previous cholecystectomy eroding into the bowel and leading to intraluminal mechanical bowel obstruction requiring operative intervention. This case illustrates the potential risks of retained gallstones and reinforces the need to diligently collect any dropped stones at the time of initial operation. PMID:27703833

  18. Combining Multiple Rupture Models in Real-Time for Earthquake Early Warning

    NASA Astrophysics Data System (ADS)

    Minson, S. E.; Wu, S.; Beck, J. L.; Heaton, T. H.

    2015-12-01

    The ShakeAlert earthquake early warning system for the west coast of the United States is designed to combine information from multiple independent earthquake analysis algorithms in order to provide the public with robust predictions of shaking intensity at each user's location before they are affected by strong shaking. The current contributing analyses come from algorithms that determine the origin time, epicenter, and magnitude of an earthquake (On-site, ElarmS, and Virtual Seismologist). A second generation of algorithms will provide seismic line source information (FinDer), as well as geodetically-constrained slip models (BEFORES, GPSlip, G-larmS, G-FAST). These new algorithms will provide more information about the spatial extent of the earthquake rupture and thus improve the quality of the resulting shaking forecasts.Each of the contributing algorithms exploits different features of the observed seismic and geodetic data, and thus each algorithm may perform differently for different data availability and earthquake source characteristics. Thus the ShakeAlert system requires a central mediator, called the Central Decision Module (CDM). The CDM acts to combine disparate earthquake source information into one unified shaking forecast. Here we will present a new design for the CDM that uses a Bayesian framework to combine earthquake reports from multiple analysis algorithms and compares them to observed shaking information in order to both assess the relative plausibility of each earthquake report and to create an improved unified shaking forecast complete with appropriate uncertainties. We will describe how these probabilistic shaking forecasts can be used to provide each user with a personalized decision-making tool that can help decide whether or not to take a protective action (such as opening fire house doors or stopping trains) based on that user's distance to the earthquake, vulnerability to shaking, false alarm tolerance, and time required to act.

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

    NASA Astrophysics Data System (ADS)

    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

  20. Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.

    PubMed Central

    Salier, J P; Sesboüé, R; Martin-Mondière, C; Daveau, M; Cesaro, P; Cavelier, B; Coquerel, A; Legrand, L; Goust, J M; Degos, J D

    1986-01-01

    In some Caucasian populations, multiple sclerosis (MS) susceptibility has been independently related to given alleles of HLA or Gm systems that respectively code for major histocompatibility complex class I and II antigens or immunoglobulin G heavy chains. Whether given combinations of alleles at both series of loci simultaneously influence MS susceptibility and/or severity was investigated by comparing 147 French MS patients and 226 geographically-matched healthy controls. The G2m(-23)/HLA-B35 phenotype and G1m(-1)/HLA-B7(-)/HLA-DR2 phenotype were respectively associated with significant protection against (relative risk = 0.05) and susceptibility to (relative risk = 4.3) MS. When considering MS severity, the presence of HLA-B7 antigen correlated with a more severe disease in Gm1/Gm3 heterozygous patients, but not in Gm3/Gm3 homozygous patients. Conversely, an HLA-B12-associated milder disease was restricted to Gm3/Gm3 homozygotes. These results demonstrate the combined influence on MS of genetic loci that are unlinked but immune response-associated. Combined Gm and HLA typing is very likely able to serve as a prognostic indicator in this disease. PMID:3461005

  1. Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.

    PubMed

    Salier, J P; Sesboüé, R; Martin-Mondière, C; Daveau, M; Cesaro, P; Cavelier, B; Coquerel, A; Legrand, L; Goust, J M; Degos, J D

    1986-08-01

    In some Caucasian populations, multiple sclerosis (MS) susceptibility has been independently related to given alleles of HLA or Gm systems that respectively code for major histocompatibility complex class I and II antigens or immunoglobulin G heavy chains. Whether given combinations of alleles at both series of loci simultaneously influence MS susceptibility and/or severity was investigated by comparing 147 French MS patients and 226 geographically-matched healthy controls. The G2m(-23)/HLA-B35 phenotype and G1m(-1)/HLA-B7(-)/HLA-DR2 phenotype were respectively associated with significant protection against (relative risk = 0.05) and susceptibility to (relative risk = 4.3) MS. When considering MS severity, the presence of HLA-B7 antigen correlated with a more severe disease in Gm1/Gm3 heterozygous patients, but not in Gm3/Gm3 homozygous patients. Conversely, an HLA-B12-associated milder disease was restricted to Gm3/Gm3 homozygotes. These results demonstrate the combined influence on MS of genetic loci that are unlinked but immune response-associated. Combined Gm and HLA typing is very likely able to serve as a prognostic indicator in this disease. PMID:3461005

  2. Intraluminal magnetisation of bowel by ferromagnetic particles for retraction and manipulation by magnetic probes.

    PubMed

    Wang, Z; André, P; McLean, D; Brown, S I; Florence, G J; Cuschieri, A

    2014-11-01

    Feasibility studies are needed to demonstrate that safe and effective manipulation of bowel during Minimal Access Surgery (MAS) can be obtained by use of magnetic force. This paper characterises two classes of magnetic particles: stainless steel microparticles (SS-μPs) and iron oxide nanoparticles (IO-nPs) in terms of their magnetisation, chemical composition, crystallinity, morphology and size distribution. Both magnetic particles were dispersed in a high viscosity biological liquid for intraluminal injection of bowel. Ex vivo porcine bowel segments were then retracted by permanent magnetic probes of 5.0 and 10mm diameter. Strong retraction forces reaching 6N maximum were obtained by magnetic fluid based on dispersion of SS-μPs. In contrast, the IO-nP-based magnetic liquid generated less attraction force, due to both lower magnetic and solution properties of the IO-nPs. The comparison of the two particles allowed the identification of the rules to engineer the next generation of particles. The results with SS-μPs provide proof on concept that intraluminal injection of magnetic fluid can generate sufficient force for efficient bowel retraction. Thereafter we shall carry out in vivo animal studies for efficacy and safety of both types of ferrofluids. PMID:25169469

  3. In vivo study of novel nanofibrous intra-luminal guidance channels to promote nerve regeneration

    NASA Astrophysics Data System (ADS)

    Koh, H. S.; Yong, T.; Teo, W. E.; Chan, C. K.; Puhaindran, M. E.; Tan, T. C.; Lim, A.; Lim, B. H.; Ramakrishna, S.

    2010-08-01

    A novel nanofibrous construct for promoting peripheral nerve repair was fabricated and tested in a rat sciatic nerve defect model. The conduit is made out of bilayered nanofibrous membranes with the nanofibers longitudinally aligned in the lumen and randomly oriented on the outer surface. The intra-luminal guidance channel is made out of aligned nanofibrous yarns. In addition, biomolecules such as laminin and nerve growth factor were incorporated in the nanofibrous nerve construct to determine their efficacy in in vivo nerve regeneration. Muscle reinnervation, withdrawal reflex latency, histological, axon density and electrophysiology tests were carried out to compare the efficacy of nanofibrous constructs with an autograft. Our study showed mixed results when comparing the artificial constructs with an autograft. In some cases, the nanofibrous conduit with aligned nanofibrous yarn as an intra-luminal guidance channel performs better than the autograft in muscle reinnervation and withdrawal reflex latency tests. However, the axon density count is highest in the autograft at mid-graft. Functional recovery was improved with the use of the nerve construct which suggested that this nerve implant has the potential for clinical usage in reconstructing peripheral nerve defects.

  4. Effectiveness of microwave moist-heat intraluminal disinfection of CAPD connectology.

    PubMed

    Fessia, S L; Grabowy, R S; Bousquet, G G

    1991-01-01

    Studies were performed to quantify the microbial population reduction achieved with the Peritoneal Dialysis Moist Heat Device (PDM-1). This microwave method is used to disinfect the inner lumen of connectors used in the exchange process for continuous ambulatory peritoneal dialysis (CAPD). The microwave heating technique was evaluated on different connector systems containing a suspension of 10(6) microorganisms. The most prevalent and most problematic peritonitis-causative microorganisms were tested. After heating, the degree of disinfection was measured by enumerating bacterial colonies of the treated suspension. D-value determinations were then performed. The D-value for spores of A. niger was found to be 7.1 seconds for one type of connector system. Two other connector systems containing different intraluminal solution volumes were also tested using spores of A. niger and D-values were determined to be 7.6 seconds and 9.5 seconds, respectively. Other organisms tested were determined to have D-value times shorter than that for A. niger. Rapid heating of the solution contained within the CAPD connectors is a key characteristic of the microwave technique since temperatures rise high enough for destruction of microorganisms while leaving the plastic safe to touch. Thus, this technique is a safe and effective method for providing intraluminal disinfection. PMID:1680426

  5. Intraluminal magnetisation of bowel by ferromagnetic particles for retraction and manipulation by magnetic probes.

    PubMed

    Wang, Z; André, P; McLean, D; Brown, S I; Florence, G J; Cuschieri, A

    2014-11-01

    Feasibility studies are needed to demonstrate that safe and effective manipulation of bowel during Minimal Access Surgery (MAS) can be obtained by use of magnetic force. This paper characterises two classes of magnetic particles: stainless steel microparticles (SS-μPs) and iron oxide nanoparticles (IO-nPs) in terms of their magnetisation, chemical composition, crystallinity, morphology and size distribution. Both magnetic particles were dispersed in a high viscosity biological liquid for intraluminal injection of bowel. Ex vivo porcine bowel segments were then retracted by permanent magnetic probes of 5.0 and 10mm diameter. Strong retraction forces reaching 6N maximum were obtained by magnetic fluid based on dispersion of SS-μPs. In contrast, the IO-nP-based magnetic liquid generated less attraction force, due to both lower magnetic and solution properties of the IO-nPs. The comparison of the two particles allowed the identification of the rules to engineer the next generation of particles. The results with SS-μPs provide proof on concept that intraluminal injection of magnetic fluid can generate sufficient force for efficient bowel retraction. Thereafter we shall carry out in vivo animal studies for efficacy and safety of both types of ferrofluids.

  6. Multiple sequence alignment based on combining genetic algorithm with chaotic sequences.

    PubMed

    Gao, C; Wang, B; Zhou, C J; Zhang, Q

    2016-01-01

    In bioinformatics, sequence alignment is one of the most common problems. Multiple sequence alignment is an NP (nondeterministic polynomial time) problem, which requires further study and exploration. The chaos optimization algorithm is a type of chaos theory, and a procedure for combining the genetic algorithm (GA), which uses ergodicity, and inherent randomness of chaotic iteration. It is an efficient method to solve the basic premature phenomenon of the GA. Applying the Logistic map to the GA and using chaotic sequences to carry out the chaotic perturbation can improve the convergence of the basic GA. In addition, the random tournament selection and optimal preservation strategy are used in the GA. Experimental evidence indicates good results for this process. PMID:27420977

  7. Transfer matrices combined with Green's functions for the multiple-scattering simulation of electronic projection imaging

    NASA Astrophysics Data System (ADS)

    Mayer, A.; Vigneron, J.-P.

    1999-07-01

    Electronic projection imaging is described in the framework of a multiple-scattering theory, by using a combination of transfer-matrix and Green's-function formalisms. The transfer-matrix methodology is used to compute the wave propagation within the tip and object scattering region, while the Green's-function formalism is used to describe the electron projection from the scatterers towards a distant imaging screen. This full-order theory is needed to overcome the limits of the first Born approximation and deal with three-dimensional effects. In particular, this approach is able to account for sucking-in and standing-wave effects taking place close to or inside the object. The simulation of the electronic diffraction by a model nanoscopic carbon rod, eventually containing inhomogeneities, is considered in detail.

  8. A combined planning and self-efficacy intervention to promote physical activity: a multiple mediation analysis.

    PubMed

    Koring, Milena; Richert, Jana; Parschau, Linda; Ernsting, Anna; Lippke, Sonia; Schwarzer, Ralf

    2012-01-01

    Many individuals are motivated to improve their physical activity levels, but often fail to act upon their intention. Interventions fostering volitional strategies, such as action planning, coping planning, and self-efficacy beliefs, can help to translate intentions into behavior. This study examines the effectiveness and the mechanisms of a combined planning and self-efficacy intervention to promote physical activity among motivated individuals. Participants (N = 883) were randomly assigned to the intervention or to a waiting-list control condition. Multivariate analysis of variance revealed that the intervention resulted in significantly more physical activity, higher levels of action planning, coping planning, and volitional self-efficacy beliefs (p < 0.01). In addition, multiple mediation analysis showed that action planning, coping planning, and volitional self-efficacy mediate between the intervention and physical activity. The study shows that the intervention successfully fostered physical activity and unfolds the underlying self-regulatory mechanisms of the intervention's effectiveness.

  9. Multiple sequence alignment based on combining genetic algorithm with chaotic sequences.

    PubMed

    Gao, C; Wang, B; Zhou, C J; Zhang, Q

    2016-06-24

    In bioinformatics, sequence alignment is one of the most common problems. Multiple sequence alignment is an NP (nondeterministic polynomial time) problem, which requires further study and exploration. The chaos optimization algorithm is a type of chaos theory, and a procedure for combining the genetic algorithm (GA), which uses ergodicity, and inherent randomness of chaotic iteration. It is an efficient method to solve the basic premature phenomenon of the GA. Applying the Logistic map to the GA and using chaotic sequences to carry out the chaotic perturbation can improve the convergence of the basic GA. In addition, the random tournament selection and optimal preservation strategy are used in the GA. Experimental evidence indicates good results for this process.

  10. Detecting Causality by Combined Use of Multiple Methods: Climate and Brain Examples

    PubMed Central

    Hirata, Yoshito; Amigó, José M.; Matsuzaka, Yoshiya; Yokota, Ryo; Mushiake, Hajime; Aihara, Kazuyuki

    2016-01-01

    Identifying causal relations from time series is the first step to understanding the behavior of complex systems. Although many methods have been proposed, few papers have applied multiple methods together to detect causal relations based on time series generated from coupled nonlinear systems with some unobserved parts. Here we propose the combined use of three methods and a majority vote to infer causality under such circumstances. Two of these methods are proposed here for the first time, and all of the three methods can be applied even if the underlying dynamics is nonlinear and there are hidden common causes. We test our methods with coupled logistic maps, coupled Rössler models, and coupled Lorenz models. In addition, we show from ice core data how the causal relations among the temperature, the CH4 level, and the CO2 level in the atmosphere changed in the last 800,000 years, a conclusion also supported by irregularly sampled data analysis. Moreover, these methods show how three regions of the brain interact with each other during the visually cued, two-choice arm reaching task. Especially, we demonstrate that this is due to bottom up influences at the beginning of the task, while there exist mutual influences between the posterior medial prefrontal cortex and the presupplementary motor area. Based on our results, we conclude that identifying causality with an appropriate ensemble of multiple methods ensures the validity of the obtained results more firmly. PMID:27380515

  11. Combination therapy with thalidomide, incadronate, and dexamethasone for relapsed or refractory multiple myeloma.

    PubMed

    Ochiai, Naoya; Yamada, Noriko; Uchida, Ryo; Fuchida, Shin-ichi; Okano, Akira; Hatsuse, Mayumi; Okamoto, Masashi; Ashihara, Eishi; Shimazaki, Chihiro

    2005-10-01

    The feasibility and efficacy of a combination of thalidomide, incadronate, and dexamethasone (TID) were studied in 12 patients with relapsed or refractory multiple myeloma. The protocol, consisting of 300 mg/day of thalidomide administered orally, intravenous incadronate (10 mg/day) administered weekly, and 12 mg/day dexamethasone for 4 days, was repeated every 3 weeks. Evaluations of efficacy and toxicity were carried out every 3 weeks and were continued for 3 cycles. Three patients were excluded during the study because of apnea, severe somnolence, and pancytopenia. Of 9 evaluated patients, the partial responses achieved in 3 patients and the minor responses achieved in 4 patients corresponded to a response rate of 78% according to the criteria of the European Group for Blood and Marrow Transplantation. In addition, painful osteolytic symptoms improved rapidly after 1 cycle of TID therapy in the 10 patients evaluated. These data suggest that TID is a feasible and promising therapeutic approach for refractory and relapsed multiple myeloma.

  12. Supervised segmentation of MRI brain images using combination of multiple classifiers.

    PubMed

    Ahmadvand, Ali; Sharififar, Mohammad; Daliri, Mohammad Reza

    2015-06-01

    Segmentation of different tissues is one of the initial and most critical tasks in different aspects of medical image processing. Manual segmentation of brain images resulted from magnetic resonance imaging is time consuming, so automatic image segmentation is widely used in this area. Ensemble based algorithms are very reliable and generalized methods for classification. In this paper, a supervised method named dynamic classifier selection-dynamic local training local tanimoto index, which is a member of combination of multiple classifiers (CMCs) methods is proposed. The proposed method uses dynamic local training sets instead of a full statics one and also it change the classifier rank criterion properly for brain tissue classification. Selection policy for combining the different decisions is implemented here and the K-nearest neighbor algorithm is used to find the best local classifier. Experimental results show that the proposed method can classify the real datasets of the internet brain segmentation repository better than all single classifiers in ensemble and produces significantly improvement on other CMCs methods. PMID:26130310

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

    PubMed

    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.

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

    PubMed

    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. PMID:26104162

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

    PubMed Central

    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).

  16. Global multiple protein-protein interaction network alignment by combining pairwise network alignments

    PubMed Central

    2015-01-01

    Background A wealth of protein interaction data has become available in recent years, creating an urgent need for powerful analysis techniques. In this context, the problem of finding biologically meaningful correspondences between different protein-protein interaction networks (PPIN) is of particular interest. The PPIN of a species can be compared with that of other species through the process of PPIN alignment. Such an alignment can provide insight into basic problems like species evolution and network component function determination, as well as translational problems such as target identification and elucidation of mechanisms of disease spread. Furthermore, multiple PPINs can be aligned simultaneously, expanding the analytical implications of the result. While there are several pairwise network alignment algorithms, few methods are capable of multiple network alignment. Results We propose SMAL, a MNA algorithm based on the philosophy of scaffold-based alignment. SMAL is capable of converting results from any global pairwise alignment algorithms into a MNA in linear time. Using this method, we have built multiple network alignments based on combining pairwise alignments from a number of publicly available (pairwise) network aligners. We tested SMAL using PPINs of eight species derived from the IntAct repository and employed a number of measures to evaluate performance. Additionally, as part of our experimental investigations, we compared the effectiveness of SMAL while aligning up to eight input PPINs, and examined the effect of scaffold network choice on the alignments. Conclusions A key advantage of SMAL lies in its ability to create MNAs through the use of pairwise network aligners for which native MNA implementations do not exist. Experiments indicate that the performance of SMAL was comparable to that of the native MNA implementation of established methods such as IsoRankN and SMETANA. However, in terms of computational time, SMAL was significantly faster

  17. Combining multiple regression and principal component analysis for accurate predictions for column ozone in Peninsular Malaysia

    NASA Astrophysics Data System (ADS)

    Rajab, Jasim M.; MatJafri, M. Z.; Lim, H. S.

    2013-06-01

    This study encompasses columnar ozone modelling in the peninsular Malaysia. Data of eight atmospheric parameters [air surface temperature (AST), carbon monoxide (CO), methane (CH4), water vapour (H2Ovapour), skin surface temperature (SSKT), atmosphere temperature (AT), relative humidity (RH), and mean surface pressure (MSP)] data set, retrieved from NASA's Atmospheric Infrared Sounder (AIRS), for the entire period (2003-2008) was employed to develop models to predict the value of columnar ozone (O3) in study area. The combined method, which is based on using both multiple regressions combined with principal component analysis (PCA) modelling, was used to predict columnar ozone. This combined approach was utilized to improve the prediction accuracy of columnar ozone. Separate analysis was carried out for north east monsoon (NEM) and south west monsoon (SWM) seasons. The O3 was negatively correlated with CH4, H2Ovapour, RH, and MSP, whereas it was positively correlated with CO, AST, SSKT, and AT during both the NEM and SWM season periods. Multiple regression analysis was used to fit the columnar ozone data using the atmospheric parameter's variables as predictors. A variable selection method based on high loading of varimax rotated principal components was used to acquire subsets of the predictor variables to be comprised in the linear regression model of the atmospheric parameter's variables. It was found that the increase in columnar O3 value is associated with an increase in the values of AST, SSKT, AT, and CO and with a drop in the levels of CH4, H2Ovapour, RH, and MSP. The result of fitting the best models for the columnar O3 value using eight of the independent variables gave about the same values of the R (≈0.93) and R2 (≈0.86) for both the NEM and SWM seasons. The common variables that appeared in both regression equations were SSKT, CH4 and RH, and the principal precursor of the columnar O3 value in both the NEM and SWM seasons was SSKT.

  18. Multiple Serum Cytokine Profiling to Identify Combinational Diagnostic Biomarkers in Attacks of Familial Mediterranean Fever.

    PubMed

    Koga, Tomohiro; Migita, Kiyoshi; Sato, Shuntaro; Umeda, Masataka; Nonaka, Fumiaki; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Masumoto, Junya; Agematsu, Kazunaga; Yachie, Akihiro; Yoshiura, Koh-Ichiro; Eguchi, Katsumi; Kawakami, Atsushi

    2016-04-01

    The precise cytokine networks in the serum of individuals with familial Mediterranean fever (FMF) that are associated with its pathogenesis have been unknown. Here, we attempted to identify specific biomarkers to diagnose or assess disease activity in FMF patients. We measured serum levels of 45 cytokines in 75 FMF patients and 40 age-matched controls by multisuspension cytokine array. FMF in "attack" or "remission" was classified by Japan College of Rheumatology-certified rheumatologists according to the Tel Hashomer criteria. Cytokines were ranked by their importance by a multivariate classification algorithm. We performed a logistic regression analysis to determine specific biomarkers for discriminating FMF patients in attack. To identify specific molecular networks, we performed a cluster analysis of each cytokine. Twenty-nine of the 45 cytokines were available for further analyses. Eight cytokines' serum levels were significantly elevated in the FMF attack versus healthy control group. Nine cytokines were increased in FMF attack compared to FMF remission. Multivariate classification algorithms followed by a logistic regression analysis revealed that the combined measurement of IL-6, IL-18, and IL-17 distinguished FMF patients in attack from the controls with the highest accuracy (sensitivity 89.2%, specificity 100%, and accuracy 95.5%). Among the FMF patients, the combined measurement of IL-6, G-CSF, IL-10, and IL-12p40 discriminated febrile attack periods from remission periods with the highest accuracy (sensitivity 75.0%, specificity 87.9%, and accuracy 84.0%). Our data identified combinational diagnostic biomarkers in FMF patients based on the measurement of multiple cytokines. These findings help to improve the diagnostic performance of FMF in daily practice and extend our understanding of the activation of the inflammasome leading to enhanced cytokine networks. PMID:27100444

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    2011-01-01

    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's treatment through a highly

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

    NASA Astrophysics Data System (ADS)

    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

  2. Assessment of Wall Elasticity Variations on Intraluminal Haemodynamics in Descending Aortic Dissections Using a Lumped-Parameter Model

    PubMed Central

    Rudenick, Paula A.; Bijnens, Bart H.; Segers, Patrick; García-Dorado, David; Evangelista, Arturo

    2015-01-01

    Descending aortic dissection (DAD) is associated with high morbidity and mortality rates. Aortic wall stiffness is a variable often altered in DAD patients and potentially involved in long-term outcome. However, its relevance is still mostly unknown. To gain more detailed knowledge of how wall elasticity (compliance) might influence intraluminal haemodynamics in DAD, a lumped-parameter model was developed based on experimental data from a pulsatile hydraulic circuit and validated for 8 clinical scenarios. Next, the variations of intraluminal pressures and flows were assessed as a function of wall elasticity. In comparison with the most rigid-wall case, an increase in elasticity to physiological values was associated with a decrease in systolic and increase in diastolic pressures of up to 33% and 63% respectively, with a subsequent decrease in the pressure wave amplitude of up to 86%. Moreover, it was related to an increase in multidirectional intraluminal flows and transition of behaviour as 2 parallel vessels towards a vessel with a side-chamber. The model supports the extremely important role of wall elasticity as determinant of intraluminal pressures and flow patterns for DAD, and thus, the relevance of considering it during clinical assessment and computational modelling of the disease. PMID:25881158

  3. Particle acceleration by combined diffusive shock acceleration and downstream multiple magnetic island acceleration

    NASA Astrophysics Data System (ADS)

    Zank, G. P.; Hunana, P.; Mostafavi, P.; le Roux, J. A.; Li, Gang; Webb, G. M.; Khabarova, O.

    2015-09-01

    As a consequence of the evolutionary conditions [28; 29], shock waves can generate high levels of downstream vortical turbulence. Simulations [32-34] and observations [30; 31] support the idea that downstream magnetic islands (also called plasmoids or flux ropes) result from the interaction of shocks with upstream turbulence. Zank et al. [18] speculated that a combination of diffusive shock acceleration (DSA) and downstream reconnection-related effects associated with the dynamical evolution of a “sea of magnetic islands” would result in the energization of charged particles. Here, we utilize the transport theory [18; 19] for charged particles propagating diffusively in a turbulent region filled with contracting and reconnecting plasmoids and small-scale current sheets to investigate a combined DSA and downstream multiple magnetic island charged particle acceleration mechanism. We consider separately the effects of the anti-reconnection electric field that is a consequence of magnetic island merging [17], and magnetic island contraction [14]. For the merging plasmoid reconnection- induced electric field only, we find i) that the particle spectrum is a power law in particle speed, flatter than that derived from conventional DSA theory, and ii) that the solution is constant downstream of the shock. For downstream plasmoid contraction only, we find that i) the accelerated particle spectrum is a power law in particle speed, flatter than that derived from conventional DSA theory; ii) for a given energy, the particle intensity peaks downstream of the shock, and the peak location occurs further downstream of the shock with increasing particle energy, and iii) the particle intensity amplification for a particular particle energy, f(x, c/c0)/f(0, c/c0), is not 1, as predicted by DSA theory, but increases with increasing particle energy. These predictions can be tested against observations of electrons and ions accelerated at interplanetary shocks and the heliospheric

  4. Combining the Masking and Scaffolding Modalities of Colloidal Crystal Templates: Plasmonic Nanoparticle Arrays with Multiple Periodicities

    PubMed Central

    2015-01-01

    Surface patterns with prescribed structures and properties are highly desirable for a variety of applications. Increasing the heterogeneity of surface patterns is frequently required. This work opens a new avenue toward creating nanoparticle arrays with multiple periodicities by combining two generally separately applied modalities (i.e., scaffolding and masking) of a monolayer colloidal crystal (MCC) template. Highly ordered, loosely packed binary and ternary surface patterns are realized by a single-step thermal treatment of a gold thin-film-coated MCC and a nonclose-packed MCC template. Our approach enables control of the parameters defining these nanoscale binary and ternary surface patterns, such as particle size, shape, and composition, as well as the interparticle spacing. This technique enables preparation of well-defined binary and ternary surface patterns to achieve customized plasmonic properties. Moreover, with their easy programmability and excellent scalability, the binary and ternary surface patterns presented here could have valuable applications in nanophotonics and biomedicine. Specific examples include biosensing via surface-enhanced Raman scattering, fabrication of plasmonic-enhanced solar cells, and water splitting. PMID:25620849

  5. Combining Evidence of Preferential Gene-Tissue Relationships from Multiple Sources

    PubMed Central

    Guo, Jing; Hammar, Mårten; Öberg, Lisa; Padmanabhuni, Shanmukha S.; Bjäreland, Marcus; Dalevi, Daniel

    2013-01-01

    An important challenge in drug discovery and disease prognosis is to predict genes that are preferentially expressed in one or a few tissues, i.e. showing a considerably higher expression in one tissue(s) compared to the others. Although several data sources and methods have been published explicitly for this purpose, they often disagree and it is not evident how to retrieve these genes and how to distinguish true biological findings from those that are due to choice-of-method and/or experimental settings. In this work we have developed a computational approach that combines results from multiple methods and datasets with the aim to eliminate method/study-specific biases and to improve the predictability of preferentially expressed human genes. A rule-based score is used to merge and assign support to the results. Five sets of genes with known tissue specificity were used for parameter pruning and cross-validation. In total we identify 3434 tissue-specific genes. We compare the genes of highest scores with the public databases: PaGenBase (microarray), TiGER (EST) and HPA (protein expression data). The results have 85% overlap to PaGenBase, 71% to TiGER and only 28% to HPA. 99% of our predictions have support from at least one of these databases. Our approach also performs better than any of the databases on identifying drug targets and biomarkers with known tissue-specificity. PMID:23950964

  6. A new approach for combining knowledge from multiple coexpression networks of microRNAs.

    PubMed

    Bhattacharyya, Malay; Das, Manali; Bandyopadhyay, Sanghamitra

    2013-08-01

    MicroRNAs (miRNAs) are a class of small noncoding RNAs that are known to have critical functions across various biological processes. Simultaneous activities of multiple miRNAs can be monitored from their expression profiles under various conditions. We often build up coexpression networks from such profiles. Unfortunately, due to the change of experimental setups (or conditions), the expression profiles do change, and consequently, the patterns of the coexpression networks vary. To obtain a robust functional relationship between miRNAs, by integrating different coexpression networks in a systems biology approach, we have to combine them properly. Here, we evaluate the state-of-the-art techniques and propose a novel integrative measure, and a corresponding methodology, that might be useful for identifying the dependence between coexpression and functional similarity. We establish the results by evaluating the expression profiles of miRNAs taken from bone marrow samples of patients with leukemia. The findings highlight the potential of the integrative algorithm in analyzing the expression profiles of miRNAs for further study.

  7. Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results

    PubMed Central

    Melodelima, David; Prat, Frederic; Fritsch, Jacques; Theillere, Yves; Cathignol, Dominique

    2008-01-01

    Background Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap. Methods Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Single lesions extend from the transducer surface up to 10 mm in depth when applying an intensity of 14 W/cm2 for 10s. A lumen inside the therapy applicator provides path for an endoscopic ultrasound imaging probe operating at a frequency of 12 MHz. The mechanical rotation of the applicator around its axis enables treatment of sectorial or cylindrical volumes. This method is thus particularly suitable for esophageal tumors that may develop only on a portion of the esophageal circumference. Previous experiments were conducted from bench to in vivo studies on pig esophagi. Results Here we report clinical results obtained on four patients included in a pilot study. The treatment of esophageal tumors was performed under fluoroscopic guidance and ultrasound imaging. Objective tumor response was obtained in all cases and a complete necrosis of a tumor was obtained in one case. All patients recovered uneventfully and dysphagia improved significantly within 15 days, allowing for resuming a solid diet in three cases. Conclusion This clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus. PMID:18533990

  8. Strategies to reduce intraluminal clot formation in endoscopically harvested saphenous veins

    PubMed Central

    Brown, Emile N.; Kon, Zachary N.; Tran, Richard; Burris, Nicholas S.; Gu, Junyen; Laird, Patrick; Brazio, Philip S.; Kallam, Seeta; Schwartz, Kimberly; Bechtel, Lisa; Joshi, Ashish; Zhang, Shaosong; Poston, Robert S.

    2010-01-01

    Objective Residual clot strands within the excised saphenous vein are an increasingly recognized sequela of endoscopic vein harvest. We hypothesized that endoscopic visualization facilitated by sealed carbon dioxide insufflation causes stagnation of blood within the saphenous vein. In the absence of prior heparin administration, this stasis provokes clot formation. Methods Forty consecutive patients having coronary artery bypass grafting underwent endoscopic vein harvest using sealed (Guidant VasoView, n = 30; Guidant Corp, Minneapolis, Minn) or open (Datascope ClearGlide, n = 10; Datascope Corp, Montvale, NJ) carbon dioxide insufflation followed by ex vivo assessment of intraluminal saphenous vein clot via optical coherence tomography. In the sealed carbon dioxide insufflation groups, clot formation was compared with (preheparinized, n = 20) and without (control, n = 10) heparin administration before endoscopic vein harvest, either at a fixed dose or titrated to an activated clotting time greater than 300 seconds. Risk factors for clot formation were assessed. Results Residual saphenous vein clot was a universal finding in control veins (sealed carbon dioxide insufflation endoscopic vein harvest without preheparinization). At either dose used, heparin given before endoscopic vein harvest significantly decreased saphenous vein clot burden. A similar reduction in clot was observed when using open carbon dioxide insufflation endoscopic vein harvest without preheparinization. Intraoperative blood loss and blood product requirements were similar in all groups. Patient age and preoperative maximum amplitude of the thrombelastography tracing showed a linear correlation with saphenous vein clot volume. Conclusion By enabling the quantification of this issue as never before possible, optical coherence tomography screening revealed that intraluminal saphenous vein clot is frequently found after endoscopic vein harvest. Systemic heparinization before harvest or an open

  9. The use of intraluminal strain gauges for recording ambulant small bowel motility.

    PubMed

    Gill, R C; Kellow, J E; Browning, C; Wingate, D L

    1990-04-01

    Perfused-tube manometry has hitherto been the standard technique for recording intraluminal intestinal pressure in humans, but it is unsuitable for ambulant use. The aim of our study was to evaluate the ability of resistive strain gauge transducers attached to a fine catheter to detect pressure change. Simultaneous strain gauge and perfused-tube manometry was performed on six fasting subjects; in four, strain gauge activation was continuous and in two, the transducers were activated in a pulsed mode with data encoded as a pulse train with an approximate frequency of 20 Hz. Eight thousand eight hundred eighty-eight pressure waves were recorded by strain gauge, of which 96% were detected by perfused-tube manometry. There was good agreement in both phases II and III of the migrating motor complex. The amplitude of pressure waves recorded by strain gauge was slightly but significantly greater. A proportion (14-17%) of pressure waves recorded by strain gauge were bifid; this was not seen with the perfused tube. These differences are best explained by the greater sensitivity and more rapid rise time of the strain gauges. There was no loss of fidelity in the pulse-interval recording mode. A seventh subject underwent a continuous 72-h recording with the strain gauge catheter attached to a battery-operated encoder and magnetic tape cassette recorder and was freely ambulant during this period. The procedure was well tolerated and motility patterns could be clearly identified. We conclude that intraluminal strain gauge catheters are suitable for prolonged use in ambulant subjects and produce data that are closely comparable to the data acquired from perfused-tube manometry under laboratory conditions. PMID:2333973

  10. In vitro additive effect of imipenem combined with vancomycin against multiple-drug resistant, coagulase-negative Staphylococci.

    PubMed

    Traub, W H; Spohr, M; Bauer, D

    1986-09-01

    Imipenem combined with vancomycin resulted in a marked additive effect in vitro against 9 clinical isolates of multiple-drug resistant (MDR), coagulase-negative staphylococci, including strains resistant against imipenem. The additive effect was documented with the aid of checkerboard MIC determinations and with time kill curve experiments. In contrast, imipenem combined with vancomycin merely yielded weak additive or indifferent effects against 10 MDR isolates of Staphylococcus aureus, all of which were susceptible to imipenem.

  11. Quantifying the combined effects of multiple extreme floods on river channel geometry and on flood hazards

    NASA Astrophysics Data System (ADS)

    Guan, Mingfu; Carrivick, Jonathan L.; Wright, Nigel G.; Sleigh, P. Andy; Staines, Kate E. H.

    2016-07-01

    Effects of flood-induced bed elevation and channel geometry changes on flood hazards are largely unexplored, especially in the case of multiple floods from the same site. This study quantified the evolution of river channel and floodplain geometry during a repeated series of hypothetical extreme floods using a 2D full hydro-morphodynamic model (LHMM). These experiments were designed to examine the consequences of channel geometry changes on channel conveyance capacity and subsequent flood dynamics. Our results revealed that extreme floods play an important role in adjusting a river channel to become more efficient for subsequent propagation of floods, and that in-channel scour and sediment re-distribution can greatly improve the conveyance capacity of a channel for subsequent floods. In our hypothetical sequence of floods the response of bed elevation was of net degradation, and sediment transport successively weakened even with floods of the same magnitude. Changes in river channel geometry led to significant impact on flood hydraulics and thereby flood hazards. We found that flood-induced in-channel erosion can disconnect the channel from its floodplain resulting in a reduction of floodwater storage. Thus, the frequency and extent of subsequent overbank flows and floodplain inundation decreased, which reduced downstream flood attenuation and increased downstream flood hazard. In combination and in summary, these results suggest that changes in channel capacity due to extreme floods may drive changes in flood hazard. The assumption of unchanging of river morphology during inundation modelling should therefore be open to question for flood risk management.

  12. Combining Multiple Performance Measures: Do Common Approaches Undermine Districts' Personnel Evaluation Systems? CALDER Working Paper No. 118

    ERIC Educational Resources Information Center

    Hansen, Michael; Lemke, Mariann; Sorensen, Nicholas

    2014-01-01

    Teacher and principal evaluation systems now emerging in response to federal, state and/or local policy initiatives typically require that a component of teacher evaluation be based on multiple performance metrics, which must be combined to produce summative ratings of teacher effectiveness. Districts have utilized three common approaches to…

  13. New connection method for isolating and disinfecting intraluminal path during peritoneal dialysis solution-exchange procedures.

    PubMed

    Grabowy, R S; Kelley, R; Richter, S G; Bousquet, G G; Carr, K L

    1998-01-01

    Microbiological data have been collected on the performance of a new method of isolating and disinfecting the intraluminal path at the connect/disconnect site of a peritoneal dialysis (PD)-exchange pathway. High-temperature moist-heat (HTMH) disinfection is accomplished by a new device that uses microwave energy to heat the solution contained in the pressure-tight inner lumen of PD connector pairs between the transfer-set connector-clamp and the bag-connector break-away seal. An 85 degrees C (S.D. = 2.4 degrees C, n = 10) rise in solution temperature is seen in 12 seconds, thus yielding temperatures under pressure well over 100 degrees C with starting temperatures of 25 degrees C. Connector pairs were prepared by inoculation of a solution suspension containing at least 10(6) colony-forming units (CFU) of a test micro-organism. Approximately 0.4 mL of solution was contained within the mated connector pair. Using standard D-value determination methods, data were obtained for surviving organisms versus five exposure times and a positive control to obtain a population reduction curve. Four micro-organisms (S. epidermidis, P. aeruginosa, C. albicans, and A. niger) recognized to be among the most prevalent or problematic in causing peritonitis were tested. After microwave heating, the treated solution was aseptically withdrawn from the connector pair using a needle and syringe, plated in growth media, and incubated. Population counts of CFUs after incubation were used to establish survival curves. Results showed a tenfold population reduction in less than 3 seconds for all organisms tested. A 30-second cycle time safely achieves a > 10(8) population-reduction for bacteria and yeast organisms, and a > 10(7) population reduction for fungi. One potential benefit of using this new intraluminal disinfection method is that it may help reduce peritonitis resulting from the even more problematic pathogens such as the gram-negative bacteria and fungal organisms. PMID:10649714

  14. Coherent femtosecond pulse combining of multiple parallel chirped pulse fiber amplifiers.

    PubMed

    Siiman, Leo A; Chang, Wei-zung; Zhou, Tong; Galvanauskas, Almantas

    2012-07-30

    We report on femtosecond pulse combining with up to four parallel chirped-pulse fiber amplifier channels. Active phase locking is implemented using the LOCSET (Locking of Optical Coherence by Single-detector Electronic-frequency Tagging) single detector feedback technique, resulting in 96.4%, 94.0%, and 93.9% relative combining efficiency with two, three, and four channels respectively. Theoretical and experimental analysis of combining efficiency dependence on amplitude and phase noise shows convergence to a fixed value with increasing number of channels, indicating that multi-channel pulse combining with LOCSET feedback should be scalable to very large numbers of channels.

  15. Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model

    PubMed Central

    Kloster, Brian O.; Lund, Lars; Lindholt, Jes S.

    2016-01-01

    Background The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. Methods The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. Results All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology. Conclusion In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms. PMID:27144001

  16. In Vivo Experiments with Intraluminal Ultrasound Applicator Compatible with ``Real-Time'' MR Temperature Mapping, designed for Oesophagus Tumour Ablation

    NASA Astrophysics Data System (ADS)

    Melodelima, D.; Salomir, R.; Mougenot, C.; Theillère, Y.; Moonen, C.; Cathignol, D.

    2005-03-01

    High intensity ultrasound has shown considerable ability to produce precise and deep thermal coagulation necrosis. Focused, cylindrical, spherical or plane transducers have been used to induce high temperature elevation in tissues, in order to coagulate proteins and kill cells. Magnetic Resonance Imaging (MRI) has been used, with focused transducers and cylindrical interstitial applicators, to monitor temperature distribution and provide temperature feedback control during heating procedures. The active part of intraluminal applicators is positioned very close to the target region. It is therefore essential to provide accurate monitoring of heat deposition in the tissue layer near the transducer, in order to control the extension of coagulation necrosis. The purpose of this study was to develop a 10-mm diameter intraluminal ultrasound applicator, designed to treat oesophageal cancers and compatible with "real-time" MR temperature mapping. The ultrasound applicator was tested in vivo under real time, PRF based, fast MR temperature monitoring. Experiments were performed in vivo on pig oesophagus. Respiratory-gated, MR thermometry was performed with segmented EPI gradient echo sequences. Post treatment follow up was performed with MRI in oesophagus and liver. Excellent MR compatibility was demonstrated. Thermal lesions identified on post-treatment follow up showed good correlation with on line MR thermometry data. This study demonstrated the feasibility of oesophageal thermal ablation using intraluminal ultrasound and on line MR temperature monitoring.

  17. High-dose-rate intraluminal brachytherapy for paraneoplastic autoimmune multiorgan syndrome

    PubMed Central

    Lee, Sun-Young; Kim, Jong-Hyun; Cho, Dong-Hyu

    2016-01-01

    Paraneoplastic autoimmune multiorgan syndrome (PAMS), also known as paraneoplasic pemphigus, involves the skin, internal organs and mucosa. PAMS-associated mortality may occur as a result of autoantibody formation against internal tumors and their infiltration into organs other than the skin lesions that characterize PAMS. The most common symptoms of PAMS include pain associated with continuous oral ulceration and resistance to pharmacological treatment. The present study reports the case of a 42-year-old female patient who was admitted with an 8-month history of erosive skin lesions within the trunk region, oral mucosa and vaginal mucosa. The patient was diagnosed with PAMS based on computed tomography scans and histological analyses of the lesions. The lymphoid hyperplasia in the retroperitoneum and lesions in the vaginal mucosa and trunk area were improved following pharmacological treatment and resection of the lymph node showing hyperplasia. However, the oral lesion was treated with intraluminal brachytherapy due to its resistance to long-term pharmacological treatment. The majority of the lesions were improved following treatment, in the absence of any severe side effects. In addition, neither worsening nor progression of the oral lesion was observed during the 4-year follow-up period.

  18. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice.

    PubMed

    Arai, Satoko; Kitada, Kento; Yamazaki, Tomoko; Takai, Ryosuke; Zhang, Xizhong; Tsugawa, Yoji; Sugisawa, Ryoichi; Matsumoto, Ayaka; Mori, Mayumi; Yoshihara, Yasunori; Doi, Kent; Maehara, Natsumi; Kusunoki, Shunsuke; Takahata, Akiko; Noiri, Eisei; Suzuki, Yusuke; Yahagi, Naoki; Nishiyama, Akira; Gunaratnam, Lakshman; Takano, Tomoko; Miyazaki, Toru

    2016-02-01

    Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI. PMID:26726878

  19. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice.

    PubMed

    Arai, Satoko; Kitada, Kento; Yamazaki, Tomoko; Takai, Ryosuke; Zhang, Xizhong; Tsugawa, Yoji; Sugisawa, Ryoichi; Matsumoto, Ayaka; Mori, Mayumi; Yoshihara, Yasunori; Doi, Kent; Maehara, Natsumi; Kusunoki, Shunsuke; Takahata, Akiko; Noiri, Eisei; Suzuki, Yusuke; Yahagi, Naoki; Nishiyama, Akira; Gunaratnam, Lakshman; Takano, Tomoko; Miyazaki, Toru

    2016-02-01

    Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.

  20. High-dose-rate intraluminal brachytherapy for paraneoplastic autoimmune multiorgan syndrome

    PubMed Central

    Lee, Sun-Young; Kim, Jong-Hyun; Cho, Dong-Hyu

    2016-01-01

    Paraneoplastic autoimmune multiorgan syndrome (PAMS), also known as paraneoplasic pemphigus, involves the skin, internal organs and mucosa. PAMS-associated mortality may occur as a result of autoantibody formation against internal tumors and their infiltration into organs other than the skin lesions that characterize PAMS. The most common symptoms of PAMS include pain associated with continuous oral ulceration and resistance to pharmacological treatment. The present study reports the case of a 42-year-old female patient who was admitted with an 8-month history of erosive skin lesions within the trunk region, oral mucosa and vaginal mucosa. The patient was diagnosed with PAMS based on computed tomography scans and histological analyses of the lesions. The lymphoid hyperplasia in the retroperitoneum and lesions in the vaginal mucosa and trunk area were improved following pharmacological treatment and resection of the lymph node showing hyperplasia. However, the oral lesion was treated with intraluminal brachytherapy due to its resistance to long-term pharmacological treatment. The majority of the lesions were improved following treatment, in the absence of any severe side effects. In addition, neither worsening nor progression of the oral lesion was observed during the 4-year follow-up period. PMID:27602070

  1. Modeling of intraluminal heating of biological tissue: implications for treatment of benign prostatic hyperplasia.

    PubMed

    Anvari, B; Rastegar, S; Motamedi, M

    1994-09-01

    A computer model for predicting the thermal response of a biological tissue to different intraluminal heating modalities is presented. A practical application of the model is to calculate the temperature distributions during thermal coagulation of prostate by contact heating and radiative heating. The model uses a two-dimensional axisymmetric diffusion approximation method to calculate the light distribution during radiative heating. The traditional Pennes' bio-heat equation is used to calculate the temperatures in the presence of blood flow. An implicit finite difference scheme with nonuniform grid spacings is used to solve the diffusion equation for light distribution and the bio-heat equation. Model results indicate that the radiative heating of prostate by Nd:YAG (1064 mm) and diode (810 mm) lasers can be a more effective and efficient means of coagulating a large volume of prostate, as compared to contact heating of the tissue. Blood perfusion is shown to provide a considerable heat sink as the laser exposure time is increased. Surface cooling by irrigation during the laser irradiation of tissue is shown to be an effective method for delaying tissue explosion and obtaining a large volume of coagulated tissue. The model also shows that the volume of the coagulated tissue is appreciably altered by a change in the rate of energy deposition.

  2. Combining Information from Multiple Sources in the Diagnosis of Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Risi, Susan; Lord, Catherine; Gotham, Katherine; Corsello, Christina; Chrysler, Christina; Szatmari, Peter; Cook, Edwin H., Jr.; Leventhal, Bennett L.; Pickles, Andrew

    2006-01-01

    Background: Standard case criteria are proposed for combined use of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule to diagnose autism and to define the broader category of autism spectrum disorders. Method: Single and combined Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule…

  3. Multiple engine drive for single output shaft and combining gearbox therefor

    SciTech Connect

    Soloy, J.I.

    1989-05-16

    A multiple engine drive system is described for driving a single drive shaft, comprising: multiple input shafts, each drivingly coupled to an output shaft of a different engine; a common final drive shaft; separate gear train means for drivingly coupling each of the multiple input shafts to the common final drive shaft; each separate gear train means including a separate input gear on an associated input shaft and a separate output gear on the common final drive shaft, and separate coupling means for coupling each output gear to the common final drive shaft; the coupling means comprising a separate clutch means operable to drivingly couple each output gear to the common final drive shaft when each output gear is driven by its associated input gear at a speed at least as great as that of the common final drive shaft.

  4. INTRODUCTION TO A COMBINED MULTIPLE LINEAR REGRESSION AND ARMA MODELING APPROACH FOR BEACH BACTERIA PREDICTION

    EPA Science Inventory

    Due to the complexity of the processes contributing to beach bacteria concentrations, many researchers rely on statistical modeling, among which multiple linear regression (MLR) modeling is most widely used. Despite its ease of use and interpretation, there may be time dependence...

  5. Combining Multiple Measures of Students' Opportunities to Develop Analytic, Text-Based Writing Skills

    ERIC Educational Resources Information Center

    Correnti, Richard; Matsumura, Lindsay Clare; Hamilton, Laura S.; Wang, Elaine

    2012-01-01

    Guided by evidence that teachers contribute to student achievement outcomes, researchers have been reexamining how to study instruction and the classroom opportunities teachers create for students. We describe our experience measuring students' opportunities to develop analytic, text-based writing skills. Utilizing multiple methods of data…

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

    ERIC Educational Resources Information Center

    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. A combined limit on the neutrino mass from neutrinoless double-beta decay searches in multiple isotopes

    NASA Astrophysics Data System (ADS)

    Guzowski, P.

    2016-05-01

    We set a combined limit on the effective Majorana neutrino mass mββ from experimental searches for neutrinoless double-beta decay of multiple isotopes. The limits on mββ range between 130-310 meV, depending on the choice of nuclear matrix element calculation. The limits on mββ can also be translated into a limit on the neutrino mass and mixing parameters of a fourth sterile neutrino.

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

    PubMed Central

    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. PMID:26442037

  9. Image encryption combining multiple generating sequences controlled fractional DCT with dependent scrambling and diffusion

    NASA Astrophysics Data System (ADS)

    Liang, Yaru; Liu, Guoping; Zhou, Nanrun; Wu, Jianhua

    2015-02-01

    Based on the fractional discrete cosine transform with multiple generating sequences (MGSFrDCT) and the dependent scrambling and diffusion (DSD), an image encryption algorithm is proposed, in which the multiple-generating sequences greatly enlarge the key space of the encryption system. The real-valued output of MGSFrDCT is beneficial to storage, display and transmission of the cipher-text. During the stage of confusion and diffusion, the locations and values of all MGSFrDCT transformed coefficients change due to DSD, and the initial values and fractional orders of encryption system depend not only on the cipher keys but also on the plain-image due to introduction of a disturbance factor, which allows the encryption system to resist the known-plaintext and chosen-plaintext attacks. Experimental results demonstrate that the proposed encryption algorithm is feasible, effective and secure and able to resist common classical attacks.

  10. Multiple endocrine neoplasia, type II: a combined surgical and genetic approach to treatment.

    PubMed Central

    Partington, M W; Ghent, W R; Sears, E V; Simpson, N E

    1981-01-01

    A family with multiple endocrine neoplasia, type II living in southeastern Ontario is described. Twenty individuals are known to have had medullary carcinoma of the thyroid, pheochromocytoma or both, the diagnosis of multiple endocrine neoplasia. type II is strongly suspected in five other individuals in the earlier generations. In this family the diseases seems to be transmitted by an autosomal dominant gene. A screening program set up for the family in 1977 has in 2 years identified four asymptomatic individuals (three with medullary carcinoma of the thyroid and one with this carcinoma and a pheochromocytoma). The family background, clinical picture, treatment and some of the problems of the screening program are described. PMID:7214269

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

    PubMed Central

    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

  12. Correlation Between Intraluminal Oxygen Gradient and Radial Partitioning of Intestinal Microbiota in Humans and Mice

    PubMed Central

    Albenberg, L; Esipova, TV; Judge, CP; Bittinger, K; Chen, J; Laughlin, A; Grunberg, S; Baldassano, RN; Lewis, JD; Li, H; Thom, SR; Bushman, FD; Vinogradov, SA; Wu, GD

    2014-01-01

    Background & Aims The gut microbiota is a complex and densely populated community in a dynamic environment determined by host physiology. We investigated how intestinal oxygen levels affect the composition of the fecal and mucosally adherent microbiota. Methods We used the phosphorescence quenching method and a specially designed intraluminal oxygen probe to dynamically quantify gut luminal oxygen levels in mice. 16S rRNA gene sequencing was used to characterize the microbiota in intestines of mice exposed to hyperbaric oxygen, human rectal biopsy and mucosal swab samples, and paired human stool samples. Results Average pO2 values in the lumen of the cecum were extremely low (<1 mmHg). In altering oxygenation of intestines of mice, we observed that oxygen diffused from intestinal tissue and established a radial gradient the extended from the tissue interface into the lumen. Increasing tissue oxygenation with hyperbaric oxygen altered the composition of the gut microbioita in mice. In humans, 16S rRNA gene analyses revealed an increased proportion of oxygen-tolerant organisms of the Proteobacteria and Actinobacteria phyla associated with the rectal mucosa, compared with the feces, indicating an effect of oxygenation on the microbiota. A consortium of asaccharolytic bacteria of the Firmicute and Bacteroidetes phyla, which primarily metabolize peptones and amino acids, was associated primarily with mucus. This could be due to the presence of proteinaceous substrates provided by mucus and the shedding of the intestinal epithelium. Conclusions In an analysis of intestinal microbiota of mice and humans, we observed a radial gradient of microbes linked to distribution of oxygen and nutrients provided by host tissue. PMID:25046162

  13. Flow residence time and regions of intraluminal thrombus deposition in intracranial aneurysms.

    PubMed

    Rayz, V L; Boussel, L; Ge, L; Leach, J R; Martin, A J; Lawton, M T; McCulloch, C; Saloner, D

    2010-10-01

    Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as "virtual ink" and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone. PMID:20499185

  14. Real-time gastric motility monitoring using transcutaneous intraluminal impedance measurements (TIIM).

    PubMed

    Poscente, M D; Wang, G; Filip, D; Ninova, P; Yadid-Pecht, O; Andrews, C N; Mintchev, M P

    2014-02-01

    The stomach plays a critical role in digestion, processing ingested food mechanically and breaking it up into particles, which can be effectively and efficiently processed by the intestines. When the motility of the stomach is compromised, digestion is adversely affected. This can lead to a variety of disorders. Current diagnostic techniques for gastric motility disorders are seriously lacking, and are based more on eliminating other possibilities rather than on specific tests. Presently, gastric motility can be assessed by monitoring gastric emptying, food transit, intragastric pressures, etc. The associated tests are usually stationary and of relatively short duration. The present study proposes a new method of measuring gastric motility, utilizing the attenuation of an oscillator-induced electrical signal across the gastric tissue, which is modulated by gastric contractions. The induced high-frequency oscillator signal is generated within the stomach, and is picked up transluminally by cutaneous electrodes positioned on the abdominal area connected to a custom-designed data acquisition instrument. The proposed method was implemented in two different designs: first a transoral catheter was modified to emit the signal inside the stomach; and second, a gastric retentive pill was designed to emit the signal. Both implementations were applied in vivo on two mongrel dogs (25.50 kg and 25.75 kg). Gastric contractions were registered and quantitatively compared to recordings from force transducers sutured onto the serosa of the stomach. Gastric motility indices were calculated for each minute, with transluminal impedance measurements and the measurements from the force transducers showing statistically significant (p < 0.05) Pearson correlation coefficients (0.65 ± 0.08 for the catheter-based design and 0.77 ± 0.03 for the gastric retentive pill design). These results show that transcutaneous intraluminal impedance measurement has the potential with further research

  15. Flow Residence Time and Regions of Intraluminal Thrombus Deposition in Intracranial Aneurysms

    PubMed Central

    Boussel, L.; Ge, L.; Leach, J. R.; Martin, A. J.; Lawton, M. T.; McCulloch, C.; Saloner, D.

    2010-01-01

    Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as “virtual ink” and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone. PMID:20499185

  16. Drug elimination function of rat small intestine: metabolism and intraluminal excretion.

    PubMed

    Yasuhara, M; Kurosaki, Y; Kimura, T; Sezaki, H

    1984-10-15

    The metabolic and excretory function of the small intestine was investigated after oral and intravenous administration of drugs having an aromatic amino group to rats. After administration of drugs into the intestinal loop at the initial concentration of 0.1 mM, significant excretion of their N-acetylated forms into the lumen was observed. The amount of N-acetyl forms excreted in the lumen were 39.3 +/- 3.5, 63.5 +/- 20.9 and 18.0 +/- 13.8% of disappeared drugs from the lumen for p-aminobenzoic acid (PABA), p-aminosalicylic acid and sulfanilic acid, respectively. The excretion of p-acetamidobenzoic acid (Ac-PABA) after the absorption of PABA was reduced by the coadministration with salicylic acid, benzoic acid and 2,4-dinitrophenol. Salicylic acid noncompetitively inhibited the acetylation of PABA by the intestinal N-acetyltransferase. A good correlation was found between the intestinal N-acetyltransferase activities for drugs and the intraluminal excretion of N-acetyl derivatives after intestinal absorption of drugs. These results indicate that a drug having a higher susceptibility to intestinal N-acetyltransferase would undergo a greater excretion into the lumen in its N-acetyl form after intestinal absorption. After intravenous administration of PABA at a dose of 100 mumole/kg, 4.02 +/- 0.51% of dose was excreted in the lumen as Ac-PABA in 30 min. On the other hand, a significantly smaller fraction (2.72 +/- 0.68% of dose) was excreted in the lumen after intravenous injection of 100 mumole/kg of Ac-PABA. The larger excretion of Ac-PABA after administration of PABA indicates the contribution of intestinal metabolism on the transfer of PABA not only after oral, but also after intravenous administration.

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

    ERIC Educational Resources Information Center

    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,…

  18. Ultramini nephrostomy tract combined with flexible ureterorenoscopy for the treatment of multiple renal calculi in paediatric patients

    PubMed Central

    Yang, Wen Zeng; Zhang, Yanqiao; An, Feng; Wei, Ruojing; Li, Yu; Zhang, Haisong

    2015-01-01

    Purpose To assess the safety and efficacy of an ultramini nephrostomy tract, which we were using for the first time, combined with flexible ureterorenoscopy (URS) in the treatment of pediatric patients with multiple renal calculi. Materials and Methods Twenty pediatric patients (age, ≤6 years) underwent ultramini percutaneous nephrolithotomy (PCNL) combined with flexible URS. The group had multiple renal calculi, which were bilateral in 3 cases and were located in a total of 23 sites. The calculi were located in 2 calyces in 10 cases, scattered in more than 2 calyces in 7 cases, and limited to 1 calyx in 3 cases. The average patient age was 37.35 months (range, 14-68 months). The average stone diameter was 2.0 cm (range, 1-3.0 cm). In all patients, an ultramini nephrostomy tract was established under ultrasound guidance (dilated to F10) with simultaneous sheath placement. The flexible URS was placed into the collecting system during holmium laser lithotripsy. Results When ultramini PCNL was combined with flexible ureterorenoscopic holmium laser lithotripsy, the complete stone-free rate was 87% (20/23). The average level of hemoglobin decreased to 1.0 g/dL after the operation. No blood transfusions were needed. Levels of blood urea nitrogen, creatinine, and C-reactive protein were not significantly different before and after the operation. The average duration of hospitalization was approximately 4.85 days, and all cases were followed up for 6 to 12 months. No complications were found. Conclusions Ultramini PCNL combined with flexible ureterorenoscopic holmium laser lithotripsy is a safe and effective treatment for children with multiple renal calculi. PMID:26175871

  19. Shape-based discriminative analysis of combined bilateral hippocampi using multiple object alignment

    NASA Astrophysics Data System (ADS)

    Shen, Li; Makedon, Fillia; Saykin, Andrew

    2004-05-01

    Shape analysis of hippocampi in schizophrenia has been preformed previously using the spherical harmonic SPHARM description. In these studies, the left and right hippocampi are aligned independently and the spatial relation between them is not explored. This paper presents a new SPHARM-based technique which examines not only the individual shape information of the two hippocampi but also the spatial relation between them. The left and right hippocampi are treated as a single shape configuration. A ploy-shape alignment algorithm is developed for aligning configurations of multiple SPHARM surfaces as follows: (1) the total volume is normalized; (2) the parameter space is aligned for creating the surface correspondence; (3) landmarks are created by a uniform sampling of multiple surfaces for each configuration; (4) a quaternion-based algorithm is employed to align each landmark representation to the mean configuration through the least square rotation and translation iteratively until the mean converges. After applying the poly-shape alignment algorithm, a point distribution model is applied to aligned landmarks for feature extraction. Classification is performed using Fisher's linear discriminant with an effective feature selection scheme. Applying the above procedure to our hippocampal data (14 controls versus 25 schizophrenics, all right-handed males), we achieve the best cross-validation accuracy of 92%, supporting the idea that the whole shape configuration of the two hippocampi provides valuable information in detecting schizophrenia. The results of an ROC analysis and a visualization of discriminative patterns are also included.

  20. Novel method for enhancing the destruction of environmental pollutants by the combination of multiple plasma discharges.

    PubMed

    Harling, Alice M; Glover, David J; Whitehead, J Christopher; Zhang, Kui

    2008-06-15

    A novel, multistage, dielectric, packed-bed, plasma reactor has been developed and is used to efficiently destroy environmental pollutants, such as volatile organic compounds (VOCs). A three cell plasma reactor, operated at ambient pressure and low temperatures, is found to be an effective technology for complete VOC remediation in air. The combination of plasma cells in series can significantly improve the efficiency of VOC decomposition, but the combined destruction rate is not simply an additive effect, there is a synergistic enhancement related to the effect on the plasma chemistry of sequential processing in the three cells. At the same time, the formation of byproduct such as NOx is strongly suppressed, and it is possible to remediate toluene and ethylene in air, with no detectable formation of NOx or nitric acid.

  1. A unified classifier for robust face recognition based on combining multiple subspace algorithms

    NASA Astrophysics Data System (ADS)

    Ijaz Bajwa, Usama; Ahmad Taj, Imtiaz; Waqas Anwar, Muhammad

    2012-10-01

    Face recognition being the fastest growing biometric technology has expanded manifold in the last few years. Various new algorithms and commercial systems have been proposed and developed. However, none of the proposed or developed algorithm is a complete solution because it may work very well on one set of images with say illumination changes but may not work properly on another set of image variations like expression variations. This study is motivated by the fact that any single classifier cannot claim to show generally better performance against all facial image variations. To overcome this shortcoming and achieve generality, combining several classifiers using various strategies has been studied extensively also incorporating the question of suitability of any classifier for this task. The study is based on the outcome of a comprehensive comparative analysis conducted on a combination of six subspace extraction algorithms and four distance metrics on three facial databases. The analysis leads to the selection of the most suitable classifiers which performs better on one task or the other. These classifiers are then combined together onto an ensemble classifier by two different strategies of weighted sum and re-ranking. The results of the ensemble classifier show that these strategies can be effectively used to construct a single classifier that can successfully handle varying facial image conditions of illumination, aging and facial expressions.

  2. Combined Mapping of Multiple clUsteriNg ALgorithms (COMMUNAL): A Robust Method for Selection of Cluster Number, K.

    PubMed

    Sweeney, Timothy E; Chen, Albert C; Gevaert, Olivier

    2015-11-19

    In order to discover new subsets (clusters) of a data set, researchers often use algorithms that perform unsupervised clustering, namely, the algorithmic separation of a dataset into some number of distinct clusters. Deciding whether a particular separation (or number of clusters, K) is correct is a sort of 'dark art', with multiple techniques available for assessing the validity of unsupervised clustering algorithms. Here, we present a new technique for unsupervised clustering that uses multiple clustering algorithms, multiple validity metrics, and progressively bigger subsets of the data to produce an intuitive 3D map of cluster stability that can help determine the optimal number of clusters in a data set, a technique we call COmbined Mapping of Multiple clUsteriNg ALgorithms (COMMUNAL). COMMUNAL locally optimizes algorithms and validity measures for the data being used. We show its application to simulated data with a known K, and then apply this technique to several well-known cancer gene expression datasets, showing that COMMUNAL provides new insights into clustering behavior and stability in all tested cases. COMMUNAL is shown to be a useful tool for determining K in complex biological datasets, and is freely available as a package for R.

  3. Waveguide Power Combiner Demonstration for Multiple High Power Millimeter Wave TWTAs

    NASA Technical Reports Server (NTRS)

    Wintucky, Edwin G.; Simons, Rainee N.; Lesny, Gary G.; Glass, Jeffrey L.

    2004-01-01

    NASA is presently developing nuclear reactor technologies, under Project Prometheus, which will provide spacecraft with greatly increased levels of sustained onboard power and thereby dramatically enhance the capability for future deep space exploration. The first mission planned for use of this high power technology is the Jupiter Icy Moons Orbiter (JIMO). In addition to electric propulsion and science, there will also be unprecedented onboard power available for deep space communications. A 32 GHz transmitter with 1 kW of RF output power is being considered to enable the required very high data transmission rates. One approach to achieving the 1 kW RF power, now being investigated at NASA GRC, is the possible power combining of a number of 100-1 50 W TWTs now under development. The work presented here is the results of a proof-of-concept demonstration of the power combining Ka-band waveguide circuit design and test procedure using two Ka- band TWTAs (Varian model VZA6902V3 and Logimetrics model A440/KA-1066), both of which were previously employed in data uplink evaluation terminals at 29.36 GHz for the NASA Advanced Communications Technology Satellite (ACTS) program. The characterization of the individual TWTAs and power combining demonstration were done over a 500 MHz bandwidth from 29.1 to 29.6 GHz to simulate the Deep Space Network (DSN) bandwidth of 3 1.8 to 32.3 GHz. Figures 1-3 show some of the power transfer and gain measurements of the TWTAs using a swept signal generator (Agilent 83640b) for the RF input. The input and output powers were corrected for circuit insertion losses due to the waveguide components. The RF saturated powers of both ACTS TWTAs were on the order of 120 W, which is comparable to the expected output powers of the 32 GHz TWTs. Additional results for the individual TWTAs will be presented (AM/AM, AM/PM conversion and gain compression), some of which were obtained from swept frequency and power measurements using a vector network

  4. Combining Data From Multiple Inbred Line Crosses Improves the Power and Resolution of Quantitative Trait Loci Mapping

    PubMed Central

    Li, Renhua; Lyons, Malcolm A.; Wittenburg, Henning; Paigen, Beverly; Churchill, Gary A.

    2005-01-01

    Rodent inbred line crosses are widely used to map genetic loci associated with complex traits. This approach has proven to be powerful for detecting quantitative trait loci (QTL); however, the resolution of QTL locations, typically ∼20 cM, means that hundreds of genes are implicated as potential candidates. We describe analytical methods based on linear models to combine information available in two or more inbred line crosses. Our strategy is motivated by the hypothesis that common inbred strains of the laboratory mouse are derived from a limited ancestral gene pool and thus QTL detected in multiple crosses are likely to represent shared ancestral polymorphisms. We demonstrate that the combined-cross analysis can improve the power to detect weak QTL, can narrow support intervals for QTL regions, and can be used to separate multiple QTL that colocalize by chance. Moreover, combined-cross analysis can establish the allelic states of a QTL among a set of parental lines, thus providing critical information for narrowing QTL regions by haplotype analysis. PMID:15654110

  5. Centrifugo-pneumatic multi-liquid aliquoting - parallel aliquoting and combination of multiple liquids in centrifugal microfluidics.

    PubMed

    Schwemmer, F; Hutzenlaub, T; Buselmeier, D; Paust, N; von Stetten, F; Mark, D; Zengerle, R; Kosse, D

    2015-08-01

    The generation of mixtures with precisely metered volumes is essential for reproducible automation of laboratory workflows. Splitting a given liquid into well-defined metered sub-volumes, the so-called aliquoting, has been frequently demonstrated on centrifugal microfluidics. However, so far no solution exists for assays that require simultaneous aliquoting of multiple, different liquids and the subsequent pairwise combination of aliquots with full fluidic separation before combination. Here, we introduce the centrifugo-pneumatic multi-liquid aliquoting designed for parallel aliquoting and pairwise combination of multiple liquids. All pumping and aliquoting steps are based on a combination of centrifugal forces and pneumatic forces. The pneumatic forces are thereby provided intrinsically by centrifugal transport of the assay liquids into dead end chambers to compress the enclosed air. As an example, we demonstrate simultaneous aliquoting of 1.) a common assay reagent into twenty 5 μl aliquots and 2.) five different sample liquids, each into four aliquots of 5 μl. Subsequently, the reagent and sample aliquots are simultaneously transported and combined into twenty collection chambers. All coefficients of variation for metered volumes were between 0.4%-1.0% for intra-run variations and 0.5%-1.2% for inter-run variations. The aliquoting structure is compatible to common assay reagents with a wide range of liquid and material properties, demonstrated here for contact angles between 20° and 60°, densities between 789 and 1855 kg m(-3) and viscosities between 0.89 and 4.1 mPa s. The centrifugo-pneumatic multi-liquid aliquoting is implemented as a passive fluidic structure into a single fluidic layer. Fabrication is compatible to scalable fabrication technologies such as injection molding or thermoforming and does not require any additional fabrication steps such as hydrophilic or hydrophobic coatings or integration of active valves.

  6. Centrifugo-pneumatic multi-liquid aliquoting - parallel aliquoting and combination of multiple liquids in centrifugal microfluidics.

    PubMed

    Schwemmer, F; Hutzenlaub, T; Buselmeier, D; Paust, N; von Stetten, F; Mark, D; Zengerle, R; Kosse, D

    2015-08-01

    The generation of mixtures with precisely metered volumes is essential for reproducible automation of laboratory workflows. Splitting a given liquid into well-defined metered sub-volumes, the so-called aliquoting, has been frequently demonstrated on centrifugal microfluidics. However, so far no solution exists for assays that require simultaneous aliquoting of multiple, different liquids and the subsequent pairwise combination of aliquots with full fluidic separation before combination. Here, we introduce the centrifugo-pneumatic multi-liquid aliquoting designed for parallel aliquoting and pairwise combination of multiple liquids. All pumping and aliquoting steps are based on a combination of centrifugal forces and pneumatic forces. The pneumatic forces are thereby provided intrinsically by centrifugal transport of the assay liquids into dead end chambers to compress the enclosed air. As an example, we demonstrate simultaneous aliquoting of 1.) a common assay reagent into twenty 5 μl aliquots and 2.) five different sample liquids, each into four aliquots of 5 μl. Subsequently, the reagent and sample aliquots are simultaneously transported and combined into twenty collection chambers. All coefficients of variation for metered volumes were between 0.4%-1.0% for intra-run variations and 0.5%-1.2% for inter-run variations. The aliquoting structure is compatible to common assay reagents with a wide range of liquid and material properties, demonstrated here for contact angles between 20° and 60°, densities between 789 and 1855 kg m(-3) and viscosities between 0.89 and 4.1 mPa s. The centrifugo-pneumatic multi-liquid aliquoting is implemented as a passive fluidic structure into a single fluidic layer. Fabrication is compatible to scalable fabrication technologies such as injection molding or thermoforming and does not require any additional fabrication steps such as hydrophilic or hydrophobic coatings or integration of active valves. PMID:26138211

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

    SciTech Connect

    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.

  8. Toward Complete Bacterial Genome Sequencing Through the Combined Use of Multiple Next-Generation Sequencing Platforms.

    PubMed

    Jeong, Haeyoung; Lee, Dae-Hee; Ryu, Choong-Min; Park, Seung-Hwan

    2016-01-01

    PacBio's long-read sequencing technologies can be successfully used for a complete bacterial genome assembly using recently developed non-hybrid assemblers in the absence of secondgeneration, high-quality short reads. However, standardized procedures that take into account multiple pre-existing second-generation sequencing platforms are scarce. In addition to Illumina HiSeq and Ion Torrent PGM-based genome sequencing results derived from previous studies, we generated further sequencing data, including from the PacBio RS II platform, and applied various bioinformatics tools to obtain complete genome assemblies for five bacterial strains. Our approach revealed that the hierarchical genome assembly process (HGAP) non-hybrid assembler resulted in nearly complete assemblies at a moderate coverage of ~75x, but that different versions produced non-compatible results requiring post processing. The other two platforms further improved the PacBio assembly through scaffolding and a final error correction.

  9. Multiple Imputation For Combined-Survey Estimation With Incomplete Regressors In One But Not Both Surveys

    PubMed Central

    Rendall, Michael S.; Ghosh-Dastidar, Bonnie; Weden, Margaret M.; Baker, Elizabeth H.; Nazarov, Zafar

    2013-01-01

    Within-survey multiple imputation (MI) methods are adapted to pooled-survey regression estimation where one survey has more regressors, but typically fewer observations, than the other. This adaptation is achieved through: (1) larger numbers of imputations to compensate for the higher fraction of missing values; (2) model-fit statistics to check the assumption that the two surveys sample from a common universe; and (3) specificying the analysis model completely from variables present in the survey with the larger set of regressors, thereby excluding variables never jointly observed. In contrast to the typical within-survey MI context, cross-survey missingness is monotonic and easily satisfies the Missing At Random (MAR) assumption needed for unbiased MI. Large efficiency gains and substantial reduction in omitted variable bias are demonstrated in an application to sociodemographic differences in the risk of child obesity estimated from two nationally-representative cohort surveys. PMID:24223447

  10. Combining data from multiple sources using the CUAHSI Hydrologic Information System

    NASA Astrophysics Data System (ADS)

    Tarboton, D. G.; Ames, D. P.; Horsburgh, J. S.; Goodall, J. L.

    2012-12-01

    The Consortium of Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) has developed a Hydrologic Information System (HIS) to provide better access to data by enabling the publication, cataloging, discovery, retrieval, and analysis of hydrologic data using web services. The CUAHSI HIS is an Internet based system comprised of hydrologic databases and servers connected through web services as well as software for data publication, discovery and access. The HIS metadata catalog lists close to 100 web services registered to provide data through this system, ranging from large federal agency data sets to experimental watersheds managed by University investigators. The system's flexibility in storing and enabling public access to similarly formatted data and metadata has created a community data resource from governmental and academic data that might otherwise remain private or analyzed only in isolation. Comprehensive understanding of hydrology requires integration of this information from multiple sources. HydroDesktop is the client application developed as part of HIS to support data discovery and access through this system. HydroDesktop is founded on an open source GIS client and has a plug-in architecture that has enabled the integration of modeling and analysis capability with the functionality for data discovery and access. Model integration is possible through a plug-in built on the OpenMI standard and data visualization and analysis is supported by an R plug-in. This presentation will demonstrate HydroDesktop, showing how it provides an analysis environment within which data from multiple sources can be discovered, accessed and integrated.

  11. Connectivity mapping using a combined gene signature from multiple colorectal cancer datasets identified candidate drugs including existing chemotherapies

    PubMed Central

    2015-01-01

    Background While the discovery of new drugs is a complex, lengthy and costly process, identifying new uses for existing drugs is a cost-effective approach to therapeutic discovery. Connectivity mapping integrates gene expression profiling with advanced algorithms to connect genes, diseases and small molecule compounds and has been applied in a large number of studies to identify potential drugs, particularly to facilitate drug repurposing. Colorectal cancer (CRC) is a commonly diagnosed cancer with high mortality rates, presenting a worldwide health problem. With the advancement of high throughput omics technologies, a number of large scale gene expression profiling studies have been conducted on CRCs, providing multiple datasets in gene expression data repositories. In this work, we systematically apply gene expression connectivity mapping to multiple CRC datasets to identify candidate therapeutics to this disease. Results We developed a robust method to compile a combined gene signature for colorectal cancer across multiple datasets. Connectivity mapping analysis with this signature of 148 genes identified 10 candidate compounds, including irinotecan and etoposide, which are chemotherapy drugs currently used to treat CRCs. These results indicate that we have discovered high quality connections between the CRC disease state and the candidate compounds, and that the gene signature we created may be used as a potential therapeutic target in treating the disease. The method we proposed is highly effective in generating quality gene signature through multiple datasets; the publication of the combined CRC gene signature and the list of candidate compounds from this work will benefit both cancer and systems biology research communities for further development and investigations. PMID:26356760

  12. Fatal pulmonary embolism following ultrasound-guided foam sclerotherapy combined with multiple microphlebectomies.

    PubMed

    Bruijninckx, Cornelis Ma

    2016-08-01

    Ambulatory ultrasound-guided foam sclerotherapy (UGFS) for refluxing saphenous veins is considered a safe therapy. Venous thromboembolic complications after UGFS as well as after all other ambulatory ablative venous interventions are rarely reported. This paper reports a fatal pulmonary embolism (PE) following UGFS in combination with an extended phlebectomy, and questions what measures should be taken to minimize the risk for thromboembolic complications after these procedures. In the reported case (unsuspected), extensive non-occluding atherosclerosis as well as obesity in combination with use of an oral contraceptive might have contributed to the development of the PE while the use of a β-blocker might have increased its fatal course considerably. Routine measurement of the ankle-brachial pressure index reduces the risk for undetected atherosclerosis. It appears that 'in the real world' of ambulatory phlebological treatments thromboembolic complications are more common (2.4-4.7%) and appear accompanied by post-procedural mortality. It is concluded therefore that pharmacological thromboprophylaxis appears warranted in selected cases, perhaps even routine application could be considered. Attention is drawn to the highly thrombogenic but not uncommon combination of overweight and use of oral contraceptive. Apart from applying some form of pharmacological thromboprophylaxis, technical adaptations that might prevent or reduce spill over of foam into the deep venous system should be considered. Firstly, next to adherence to the generally accepted maximum of 10 mL of foam per session, it seems prudent to maximize the injected volume of foam per site. Secondly, it seems best to inject the foam in an elevated leg without groin compression. The concentration of the sclerosant does not appear decisive in this respect, although higher concentrations appear more effective and therefore might be injected in lower volumes without compromising efficacy.

  13. Isolation of Shiga Toxin-Producing Escherichia coli from Ground Beef Using Multiple Combinations of Enrichment Broths and Selective Agars.

    PubMed

    Brusa, Victoria; Piñeyro, Pablo E; Galli, Lucía; Linares, Luciano H; Ortega, Emanuel E; Padola, Nora L; Leotta, Gerardo A

    2016-03-01

    Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens, and beef cattle are recognized as the principal reservoir. The aims of this study were (1) to identify the most sensitive combination of selective enrichment broths and agars for STEC isolation in artificially inoculated ground beef samples, and (2) to evaluate the most efficient combination(s) of methods for naturally contaminated ground beef samples. A total of 192 ground beef samples were artificially inoculated with STEC and non-stx bacterial strains. A combination of four enrichment broths and three agars were evaluated for sensitivity, specificity, and positive predictive value for STEC isolation from experimentally inoculated samples. Enrichments with either modified tryptic soy broth (mTSB) containing 8 mg/L novobiocin (mTSB-8) or modified Escherichia coli (mEC) broth followed by isolation in MacConkey agar were the most sensitive combinations for STEC isolation of artificially inoculated samples. Independently, both enrichments media followed by isolation in MacConkey were used to evaluate ground beef samples from 43 retail stores, yielding 65.1% and 58.1% stx-positive samples by RT-PCR, respectively. No difference was observed in the isolate proportions between these two methods (8/25 [32%] and 8/28 [28.6%]). Identical serotypes and stx genotypes were observed in STEC strains isolated from the same samples by either method. In this study, no single enrichment protocol was sufficient to detect all STEC in artificially inoculated samples and had considerable variation in detection ability with naturally contaminated samples. Moreover, none of the single or combinations of multiple isolation agars used were capable of identifying all STEC serogroups in either artificially inoculated or naturally occurring STEC-contaminated ground beef. Therefore, it may be prudent to conclude that there is no single method or combination of isolation methods capable of identifying all STEC serogroups

  14. [Intraluminal dilation of inferior vena cava stenosis after repair of the scimitar syndrome in an adult patient].

    PubMed

    Benito Bartolomé, Fernando; González García, Ana; Oliver Ruiz, José M

    2002-02-01

    A 39 year-old woman diagnosed with anomalous drainage of middle and lower right pulmonary veins to the inferior vena cava was corrected surgically by means of baffle with patch up to the left atrium. Early after the operation the patient related intolerance to small efforts and an episode of syncope. The cardiac catheterization demonstrated the presence of a severe stenosis in the inferior vena cava, in its union with the right atrium, that was successfully treated by means of intraluminal percutaneous dilation with a catheter of Inoue. After the procedure the gradient decreased and she improved tolerance to effort, which persisted 10 months later.

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

    PubMed Central

    Park, Yoon-Dong; Sun, Wei; Salas, Antonio; Antia, Avan; Carvajal, Cindy; Wang, Amy; Xu, Xin; Meng, Zhaojin; Zhou, Ming; Tawa, Gregory J.; Dehdashti, Jean; Zheng, Wei; Henderson, Christina M.; Zelazny, Adrian M.

    2016-01-01

    ABSTRACT 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. PMID:27486194

  16. Cumulative Risk Assessment: An Overview of Methodological Approaches for Evaluating Combined Health Effects from Exposure to Multiple Environmental Stressors

    PubMed Central

    Sexton, Ken

    2012-01-01

    Systematic evaluation of cumulative health risks from the combined effects of multiple environmental stressors is becoming a vital component of risk-based decisions aimed at protecting human populations and communities. This article briefly examines the historical development of cumulative risk assessment as an analytical tool, and discusses current approaches for evaluating cumulative health effects from exposure to both chemical mixtures and combinations of chemical and nonchemical stressors. A comparison of stressor-based and effects-based assessment methods is presented, and the potential value of focusing on viable risk management options to limit the scope of cumulative evaluations is discussed. The ultimate goal of cumulative risk assessment is to provide answers to decision-relevant questions based on organized scientific analysis; even if the answers, at least for the time being, are inexact and uncertain. PMID:22470298

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

    PubMed

    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. PMID:23348835

  18. Comparative proteogenomics: combining mass spectrometry and comparative genomics to analyze multiple genomes

    SciTech Connect

    Gupta, Nitin; Benhamida, Jamal; Bhargava, Vipul; Goodman, Daniel; Kain , Elisabeth; Kerman, Ian; Nguyen , Ngan; Ollikainen, Noah; Rodriguez, Jesse; Wang, J.; Lipton, Mary S.; Romine, Margaret F.; Bafna, Vineet; Smith, Richard D.; Pevzner, Pavel A.

    2008-07-30

    While bacterial genome annotations have significantly improved in recent years, techniques for bacterial proteome annotation (including post-translational chemical modifications, signal peptides, proteolytic events, etc.) are still in their infancy. At the same time, the number of sequenced bacterial genomes is rising sharply, far outpacing our ability to validate the predicted genes, let alone annotate bacterial proteomes. In this study, we use tandem mass spectrometry (MS/MS) to annotate the proteome of Shewanella oneidensis MR-1, an important microbe for bioremediation. In particular, we provide the first comprehensive map of post-translational modifications in a bacterial genome, including a large number of chemical modifications, signal peptide cleavages and cleavage of N-terminal methionine residues. We also detect multiple genes that were missed or assigned incorrect start positions by gene prediction programs and suggest corrections to improve the gene annotation. This study demonstrates that complementing every genome sequencing project by an MS/MS project would significantly improve both genome and proteome annotations for a reasonable cost.

  19. Combining Multiple Data Acquisition Systems to Study Corticospinal Output and Multi-segment Biomechanics.

    PubMed

    Asmussen, Michael J; Bailey, Aaron Z; Keir, Peter J; Potvin, Jim; Bergel, Tim; Nelson, Aimee J

    2016-01-09

    Transcranial magnetic stimulation techniques allow for an in-depth investigation into the neural mechanisms that underpin human behavior. To date, the use of TMS to study human movement, has been limited by the challenges related to precisely timing the delivery of TMS to features of the unfolding movement and, also, by accurately characterizing kinematics and kinetics. To overcome these technical challenges, TMS delivery and acquisition systems should be integrated with an online motion tracking system. The present manuscript details technical innovations that integrate multiple acquisition systems to facilitate and advance the use of TMS to study human movement. Using commercially available software and hardware systems, a step-by-step approach to both the hardware assembly and the software scripts necessary to perform TMS studies triggered by specific features of a movement is provided. The approach is focused on the study of upper limb, planar, multi-joint reaching movements. However, the same integrative system is amenable to a multitude of sophisticated studies of human motor control.

  20. Clinical efficacy and effectiveness of Sativex, a combined cannabinoid medicine, in multiple sclerosis-related spasticity.

    PubMed

    Oreja-Guevara, Celia

    2012-04-01

    Multiple sclerosis (MS) is associated with a wide range of disease symptoms and amongst these, spasticity is one of the most disabling and has the greatest impact on patient well-being and quality of life. Until now, available drug therapies for spasticity appear to have limited benefit and are often associated with poor tolerability. In a recent Spanish survey it was noted that multidrug therapy and a low control rate were common features for a large proportion of patients with MS-related spasticity, suggesting that currently available monotherapies lack significant activity. Sativex is a 1:1 mixture of δ-9-tetrahydrocannabinol and cannabidiol derived from Cannabis sativa chemovars, which is available as an oromucosal spray. Clinical experience with Sativex in patients with MS-related spasticity is steadily accumulating. Results from randomized, controlled trials have reported a reduction in the severity of symptoms associated with spasticity, leading to a better ability to perform daily activities and an improved perception of patients and their carers regarding functional status. These are highly encouraging findings that provide some much needed optimism for the treatment of this disabling and often painful symptom of MS. PMID:22509985

  1. Multiple congenital brachymetatarsia. A one-stage combined shortening and lengthening procedure without iliac bone graft.

    PubMed

    Kim, J S; Baek, G H; Chung, M S; Yoon, P W

    2004-09-01

    We performed nine metatarsal and three proximal phalangeal lengthenings in five patients with congenital brachymetatarsia of the first and one or two other metatarsal bones, by a one-stage combined shortening and lengthening procedure using intercalcary autogenous bone grafts from adjacent shortened metatarsal bones. Instead of the isolated lengthening of the first and the other metatarsal bones, we shortened the adjacent normal metatarsal and used the excised bone to lengthen the short toes, except for the great toe, to restore the normal parabola. One skin incision was used. All the operations were performed bilaterally and the patients were followed up for a mean period of 69.5 months (29 to 107). They all regained a nearly normal parabola and were satisfied with the cosmetic results. Our technique is straightforward and produces good cosmetic results. Satisfactory, bony union is achieved, morbidity is low, and no additional surgery is required for the removal of metal implants. PMID:15446529

  2. Mouse model of intraluminal MCAO: cerebral infarct evaluation by cresyl violet staining.

    PubMed

    Rousselet, Estelle; Kriz, Jasna; Seidah, Nabil G

    2012-01-01

    Stroke is the third cause of mortality and the leading cause of disability in the World. Ischemic stroke accounts for approximately 80% of all strokes. However, the thrombolytic tissue plasminogen activator (tPA) is the only treatment of acute ischemic stroke that exists. This led researchers to develop several ischemic stroke models in a variety of species. Two major types of rodent models have been developed: models of global cerebral ischemia or focal cerebral ischemia. To mimic ischemic stroke in patients, in whom approximately 80% thrombotic or embolic strokes occur in the territory of the middle cerebral artery (MCA), the intraluminal middle cerebral artery occlusion (MCAO) model is quite relevant for stroke studies. This model was first developed in rats by Koizumi et al. in 1986 (1). Because of the ease of genetic manipulation in mice, these models have also been developed in this species (2-3). Herein, we present the transient MCA occlusion procedure in C57/Bl6 mice. Previous studies have reported that physical properties of the occluder such as tip diameter, length, shape, and flexibility are critical for the reproducibility of the infarct volume (4). Herein, a commercial silicon coated monofilaments (Doccol Corporation) have been used. Another great advantage is that this monofilament reduces the risk to induce subarachnoid hemorrhages. Using the Zeiss stereo-microscope Stemi 2000, the silicon coated monofilament was introduced into the internal carotid artery (ICA) via a cut in the external carotid artery (ECA) until the monofilament occludes the base of the MCA. Blood flow was restored 1 hour later by removal of the monofilament to mimic the restoration of blood flow after lysis of a thromboembolic clot in humans. The extent of cerebral infarct may be evaluated first by a neurologic score and by the measurement of the infarct volume. Ischemic mice were thus analyzed for their neurologic score at different post-reperfusion times. To evaluate the infarct

  3. Combinations of Susceptibility Genes Are Associated with Higher Risk for Multiple Sclerosis and Imply Disease Course Specificity

    PubMed Central

    Akkad, Denis A.; Olischewsky, Alexandra; Reiner, Franziska; Hellwig, Kerstin; Esser, Sarika; Epplen, Jörg T.; Curk, Tomaz; Gold, Ralf; Haghikia, Aiden

    2015-01-01

    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that predominantly affects young adults. The genetic contributions to this multifactorial disease were underscored by a genome wide association study (GWAS) conducted by the International Multiple Sclerosis Genetic Consortium in a multinational cohort prompting the discovery of 57 non-MHC MS-associated common genetic variants. Hitherto, few of these newly reported variants have been replicated in larger independent patient cohorts. We genotyped a cohort of 1033 MS patients and 644 healthy controls with a consistent genetic background for the 57 non-MHC variants reported to be associated with MS by the first large GWAS as well as the HLA DRB1*1501 tagging SNP rs3135388. We robustly replicated three of the 57 non-MHC reported MS-associated single nucleotide polymorphisms (SNPs). In addition, our study revealed several genotype-genotype combinations with an evidently higher degree of disease association than the genotypes of the single SNPs. We further correlated well-defined clinical phenotypes, i.e. ataxia, visual impairment due to optic neuritis and paresis with single SNPs and genotype combinations, and identified several associations. The results may open new avenues for clinical implications of the MS associated genetic variants reported from large GWAS. PMID:26011527

  4. Hierarchical pore structure of calcium phosphate scaffolds by a combination of gel-casting and multiple tape-casting methods.

    PubMed

    Sánchez-Salcedo, S; Werner, J; Vallet-Regí, M

    2008-07-01

    The objective of this work was to design hierarchical pore structure scaffolds with potential applications in bone tissue regeneration. For that purpose, a bioceramic material such as biphasic calcium phosphate, which consists of a mixture of hydroxyapatite and beta-tricalcium phosphate, was selected. Multilayer pieces (MLP) with hierarchical pore structure were developed employing a new technique that combines gel casting and adding porogens, using multiple tape-casting methods. Pieces with functionally graded porosity were fabricated using porogens with different sizes. The porogens used were Porlat K85 and Porlat K86 with diameters <150 microm and 150-300 microm, respectively. Two types of sintered tapes, with different porosity, no cracking and enough interconnection size were selected. MLP with hierarchical pore structure were designed by the multiple tape-casting method. Interconnected pores whose sizes increase from interior tapes (1.6-3.6 microm) towards exterior tapes (20-51.5 microm) and interpenetration between tapes were achieved. Delamination or cracking were not observed after heat treatment. The flexural strength of pieces was investigated by the three-point bending test. This new combination of methods offers the possibility of manufacturing scaffolds with interconnected pore sizes ranging from 1.6 to 51.5 microm.

  5. Phase I study of pegylated liposomal doxorubicin in combination with bortezomib for Japanese patients with relapsed or refractory multiple myeloma.

    PubMed

    Kusumoto, Shigeru; Sunami, Kazutaka; Inagaki, Mitsuo; Iida, Shinsuke

    2015-06-01

    This phase I open-label study evaluated the tolerability of pegylated liposomal doxorubicin (PLD) and bortezomib combination in Japanese patients with relapsed or refractory multiple myeloma. Eligible patients (≥20 years) who had ≥1 line of prior chemotherapy received bortezomib 1.3 mg/m(2) rapid intravenous infusion on days 1, 4, 8 and 11 (each 21-day cycle), followed by PLD 30 mg/m(2) intravenous infusion on day 4 (each cycle), up to 6 cycles. Dose-limiting toxicity (DLT), defined as Grade 4 hematologic or Grade ≥3 non-hematologic, was evaluated through end of day 21. All three patients enrolled in the study developed DLTs [Grade 4 thrombocytopenia (n = 2) and Grade 3 ileus (n = 1)]. The study was, therefore, terminated without adding new patients, as per protocol-specified criteria. The most common Grade 3-4 adverse events (AEs) were hematologic, including thrombocytopenia, leucopenia, and neutropenia. The treatment was prematurely discontinued in all three patients due to AEs: Grade 3 bronchiolitis (serious AE), Grade 3 peripheral sensory neuropathy, and Grade 2 stomatitis. All patients achieved partial response (efficacy, secondary endpoint). In conclusion, the tolerability of PLD and bortezomib combination at dose levels approved in various countries was not confirmed in relapsed or refractory multiple myeloma patients from Japan.

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

    PubMed

    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/.

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

    PubMed

    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/. PMID:25951428

  8. Striking multiple synergies created by combining reduced graphene oxides and carbon nanotubes for polymer nanocomposites

    NASA Astrophysics Data System (ADS)

    Song, Ping'an; Liu, Lina; Fu, Shenyuan; Yu, Youming; Jin, Chunde; Wu, Qiang; Zhang, Yan; Li, Qian

    2013-03-01

    The extraordinary properties of carbon nanotubes (CNTs) and graphene stimulate the development of advanced composites. Recently, several studies have reported significant synergies in the mechanical, electrical and thermal conductivity properties of polymer nanocomposites by incorporating their nanohybrids. In this work, we created polypropylene nanocomposites with homogeneous dispersion of CNTs and reduced graphene oxides via a facile polymer-latex-coating plus melt-mixing strategy, and investigated their synergistic effects in their viscoelastic, gas barrier, and flammability properties. Interestingly, the results show remarkable synergies, enhancing their melt modulus and viscosity, O2 barrier, and flame retardancy properties and respectively exhibiting a synergy percentage of 15.9%, 45.3%, and 20.3%. As previously reported, we also observed remarkable synergistic effects in their tensile strength (14.3%) and Young’s modulus (27.1%), electrical conductivity (32.3%) and thermal conductivity (34.6%). These impressive results clearly point towards a new strategy to create advanced materials by adding binary combinations of different types of nanofillers.

  9. Striking multiple synergies created by combining reduced graphene oxides and carbon nanotubes for polymer nanocomposites.

    PubMed

    Song, Ping'an; Liu, Lina; Fu, Shenyuan; Yu, Youming; Jin, Chunde; Wu, Qiang; Zhang, Yan; Li, Qian

    2013-03-29

    The extraordinary properties of carbon nanotubes (CNTs) and graphene stimulate the development of advanced composites. Recently, several studies have reported significant synergies in the mechanical, electrical and thermal conductivity properties of polymer nanocomposites by incorporating their nanohybrids. In this work, we created polypropylene nanocomposites with homogeneous dispersion of CNTs and reduced graphene oxides via a facile polymer-latex-coating plus melt-mixing strategy, and investigated their synergistic effects in their viscoelastic, gas barrier, and flammability properties. Interestingly, the results show remarkable synergies, enhancing their melt modulus and viscosity, O2 barrier, and flame retardancy properties and respectively exhibiting a synergy percentage of 15.9%, 45.3%, and 20.3%. As previously reported, we also observed remarkable synergistic effects in their tensile strength (14.3%) and Young's modulus (27.1%), electrical conductivity (32.3%) and thermal conductivity (34.6%). These impressive results clearly point towards a new strategy to create advanced materials by adding binary combinations of different types of nanofillers.

  10. Formalized Conflicts Detection Based on the Analysis of Multiple Emails: An Approach Combining Statistics and Ontologies

    NASA Astrophysics Data System (ADS)

    Zakaria, Chahnez; Curé, Olivier; Salzano, Gabriella; Smaïli, Kamel

    In Computer Supported Cooperative Work (CSCW), it is crucial for project leaders to detect conflicting situations as early as possible. Generally, this task is performed manually by studying a set of documents exchanged between team members. In this paper, we propose a full-fledged automatic solution that identifies documents, subjects and actors involved in relational conflicts. Our approach detects conflicts in emails, probably the most popular type of documents in CSCW, but the methods used can handle other text-based documents. These methods rely on the combination of statistical and ontological operations. The proposed solution is decomposed in several steps: (i) we enrich a simple negative emotion ontology with terms occuring in the corpus of emails, (ii) we categorize each conflicting email according to the concepts of this ontology and (iii) we identify emails, subjects and team members involved in conflicting emails using possibilistic description logic and a set of proposed measures. Each of these steps are evaluated and validated on concrete examples. Moreover, this approach's framework is generic and can be easily adapted to domains other than conflicts, e.g. security issues, and extended with operations making use of our proposed set of measures.

  11. Pharmacokinetics of dextromethorphan after single or multiple dosing in combination with quinidine in extensive and poor metabolizers.

    PubMed

    Pope, Laura E; Khalil, M H; Berg, James E; Stiles, Mark; Yakatan, Gerald J; Sellers, Edward M

    2004-10-01

    Dextromethorphan (DM) pharmacological properties predict that the widely used cough suppressant could be used to treat several neuronal disorders, but it is rapidly metabolized after oral dosing. To find out whether quinidine (Q), a CYP2D6 inhibitor, could elevate and prolong DM plasma profiles, 2 multiple-dose studies identified the lowest oral dose of Q that could be used in a fixed combination with 3 doses of DM. A multiple-dose study in healthy subjects with an extensive or a poor enzyme metabolizer phenotype evaluated the safety and pharmacokinetic profile of a selected fixed-dose combination (AVP-923). Study 1 randomized 46 healthy subjects, who were extensive CYP2D6 metabolizers, to receive 0, 2.5, 10, 25, 50, or 75 mg Q twice daily in combination with 30 mg DM for 7 days. Plasma and urine samples were collected after the first and last doses for the assay of DM, dextrorphan (DX), and Q. Study 2 randomized 65 healthy extensive CYP2D6 metabolizers to 8 groups given twice-daily 45- or 60-mg DM doses combined with 0, 30, 45, or 60 mg Q for 7 days. The effects of increasing Q were not different with doses greater than 25 mg, whereas lower doses showed a dose-related increase in plasma DM concentrations. Urinary ratios of DM/DX showed a Q dose- and time-related increase in the number of subjects converted to the poor metabolizer phenotype that reached 100% on day 3 of dosing with 25 mg Q. Results from both studies indicated that 25 to 30 mg Q is adequate to maximally suppress O-demethylation of DM. Study 3 evaluated 7 extensive metabolizers and 2 poor metabolizers given an oral capsule every 12 hours containing 30 mg Q combined with 30 mg DM. DM plasma AUC values increased in both groups of subjects during the 8-day study. The mean urinary metabolic ratio (DM/DX) increased at least 27-fold in extensive metabolizers by day 8. There was no effect of Q on urinary metabolic ratios in poor metabolizers. Safety evaluations, including electrocardiograms, indicated that

  12. Massive Stellar Outflows From the Combined Action of Multiple Stellar Jets

    NASA Astrophysics Data System (ADS)

    Mac Low, Mordecai-Mark; Peters, T.; Klaassen, P.; Schrön, M.; Klessen, R.

    2014-01-01

    The formation of high-mass stars is usually accompanied by powerful protostellar outflows. Such high-mass outflows are not simply scaled-up versions of their lower-mass counterparts, since observations seem to suggest that the collimation degree degrades with stellar mass. Theoretically, the origins of massive outflows are not well understood because radiative feedback and gravitational fragmentation of the accretion flow around the high-mass star impede the driving of magnetic disk winds. We here present the first 3D simulation of massive star formation that simultaneously includes feedback by non-ionizing and ionizing radiation as well as a subgrid-scale model for protostellar outflows. We ran this model with the Flash adaptive mesh refinement hydrocode. We find that stars that form in a common accretion flow have aligned outflow axes, so that the individual jets of lower-mass companion stars combine to form a collective outflow. We compare our simulation to observations with synthetic H2 and CO observations and find that the morphology and kinematics of this collective outflow is very similar to observed massive outflows, such as Cepheus A and DR 21. The properties of high-mass outflows are therefore generally consistent with the formation of massive stars in gravitationally unstable accretion flows. We acknowledge support from SNF grant 200020 137896, U. Zurich grant FK-13-112, NSF grant AST11-09395, and DFG grant KL 1358/14-1, as well as SBB 811, and computing time at the LRZ (project h1343), the CSCS (Project 364), and the Juelich Supercomputing Center (project HHD14).

  13. Using multiple combined analytical techniques to characterize water extractable organic nitrogen from Lake Erhai sediment.

    PubMed

    Li, Zhang; Shengrui, Wang; Haichao, Zhao; Yanping, Li; Shouliang, Huo; Weibin, Qian; Yanli, Yang; Jie, Cheng

    2016-01-15

    In this study, UV-vis absorbance, fluorescence, and FT-IR spectroscopy were combined to characterize the components and structure of the water extractable organic nitrogen (WEON) in Lake Erhai sediment. Lake Erhai sediment WEON comprised predominantly high molecular weight WEON, with the fraction with a molecular weight>1kDa accounting for 87.7% of the total. It was mainly composed of humic acid-like substances, with fewer simple aromatic proteins. Large amounts of aliphatic and amide compounds were detected by IR in the sediments. There were more polymerizable aromatic rings and carbonyl, carboxyl, hydroxyl, and ester compounds in the high molecular weight WEON than in the low molecular weight WEON. Additionally, fluorescence regional integration results implied that the ratio PIII+V,n/PI+II+IV,n can be indirectly taken as an indicator for WEON content in Erhai sediments. Furthermore, the composition and structural characteristics of the WEON were found to be closely related with their properties in the sediment. The large amount of aliphatic compounds in the sediment as well as the relatively high humification and aromatic degree in high molecular weight WEON, stabilizes the WEON in Lake Erhai sediment. Compared with other lake sediments of different trophic statues (such as Lake Dianchi, Lake Poyang, Lake Taihu and Lake Donghu), Erhai sediment exhibited a higher degree of humification, which benefited for reducing sediment WEON releasing risk. And it can be regarded as the reason why the nutrient content in Erhai sediment is very high, but its water quality is still good.

  14. Biomechanical behaviour of cerebral aneurysm and its relation with the formation of intraluminal thrombus: a patient-specific modelling study.

    PubMed

    Wang, Xiaohong; Li, Xiaoyang

    2013-01-01

    Cerebral aneurysm is an irreversible dilatation causing intracranial haemorrhage with severe complications. It is assumed that the biomechanical factor plays a significant role in the development of cerebral aneurysm. However, reports on the correlations between the formation of intraluminal thrombus and the flow pattern, wall shear stress (WSS) distribution of the cerebral aneurysm as well as wall compliance are still limited. In this research, patient-specific numerical simulation was carried out for three cerebral aneurysms based on magnetic resonance imaging (MRI) data-sets. The interaction between pulsatile blood and aneurysm wall was taken into account. The biomechanical behaviour of cerebral aneurysm and its relation with the formation of intraluminal thrombus was studied systematically. The results of the numerical simulation indicated that the region of low blood flow velocity and the region of swirling recirculation were nearly coincident with each other. Besides, there was a significant correlation between the slow swirling flow and the location of thrombus deposition. Excessively low WSS was also found to have strong association with the regions of thrombus formation. Moreover, the relationship between cerebral aneurysm compliance and thrombus deposition was discovered. The patient-specific modelling study based on fluid-structure interaction) may provide a basis for future investigation on the prediction of thrombus formation in cerebral aneurysm. PMID:22292428

  15. Detrimental influences of intraluminally-administered sclerotic agents on surrounding tissues and peripheral nerves: an experimental study.

    PubMed

    Fujiki, Masahide; Kurita, Masakazu; Ozaki, Mine; Kawakami, Hayato; Kaji, Nobuyuki; Takushima, Akihiko; Harii, Kiyonori

    2012-09-01

    The minimally-invasive nature of sclerotherapy makes it one of the first treatment options for venous malformations, although treatment-related complications, such as peripheral nerve paralysis, have been reported in some clinical cases. However, no studies of the aetiology of the detrimental effects of intraluminally-administered sclerotic agents on the surrounding tissues, including the peripheral nerves, have yet been published. This study therefore investigated the influences of intraluminally-administered sclerotic agents on the tissues surrounding the injection site using a newly-developed rat femoral vein model. Using this model, the effects of absolute ethanol, 5% ethanolamine oleate, and 1% polidocanol were compared histologically with those of normal saline controls. Fluorescein isothiocyanate-conjugated agents were administered and the leakage of sclerotic agents through the venous wall was evaluated by fluorescence microscopy. Damage to the adjacent femoral nerve was quantitatively evaluated by counting the numbers of axons in cross-sections. All the sclerotic agents caused vascular wall injuries and leakage into the surrounding tissues. The number of axons in the femoral nerve was significantly reduced following administration of absolute ethanol or 5% ethanolamine oleate, compared with normal saline. The results of this study suggest that sclerotic agents commonly leak out the vascular lumen, and some agents can cause adjacent nerve injury. It is important to be aware of this type of complication of sclerotherapy for venous malformations when selecting appropriate therapeutic interventions.

  16. Combining different functions to describe milk, fat, and protein yield in goats using Bayesian multiple-trait random regression models.

    PubMed

    Oliveira, H R; Silva, F F; Siqueira, O H G B D; Souza, N O; Junqueira, V S; Resende, M D V; Borquis, R R A; Rodrigues, M T

    2016-05-01

    We proposed multiple-trait random regression models (MTRRM) combining different functions to describe milk yield (MY) and fat (FP) and protein (PP) percentage in dairy goat genetic evaluation by using Bayesian inference. A total of 3,856 MY, FP, and PP test-day records, measured between 2000 and 2014, from 535 first lactations of Saanen and Alpine goats, including their cross, were used in this study. The initial analyses were performed using the following single-trait random regression models (STRRM): third- and fifth-order Legendre polynomials (Leg3 and Leg5), linear B-splines with 3 and 5 knots, the Ali and Schaeffer function (Ali), and Wilmink function. Heterogeneity of residual variances was modeled considering 3 classes. After the selection of the best STRRM to describe each trait on the basis of the deviance information criterion (DIC) and posterior model probabilities (PMP), the functions were combined to compose the MTRRM. All combined MTRRM presented lower DIC values and higher PMP, showing the superiority of these models when compared to other MTRRM based only on the same function assumed for all traits. Among the combined MTRRM, those considering Ali to describe MY and PP and Leg5 to describe FP (Ali_Leg5_Ali model) presented the best fit. From the Ali_Leg5_Ali model, heritability estimates over time for MY, FP. and PP ranged from 0.25 to 0.54, 0.27 to 0.48, and 0.35 to 0.51, respectively. Genetic correlation between MY and FP, MY and PP, and FP and PP ranged from -0.58 to 0.03, -0.46 to 0.12, and 0.37 to 0.64, respectively. We concluded that combining different functions under a MTRRM approach can be a plausible alternative for joint genetic evaluation of milk yield and milk constituents in goats. PMID:27285684

  17. Combining different functions to describe milk, fat, and protein yield in goats using Bayesian multiple-trait random regression models.

    PubMed

    Oliveira, H R; Silva, F F; Siqueira, O H G B D; Souza, N O; Junqueira, V S; Resende, M D V; Borquis, R R A; Rodrigues, M T

    2016-05-01

    We proposed multiple-trait random regression models (MTRRM) combining different functions to describe milk yield (MY) and fat (FP) and protein (PP) percentage in dairy goat genetic evaluation by using Bayesian inference. A total of 3,856 MY, FP, and PP test-day records, measured between 2000 and 2014, from 535 first lactations of Saanen and Alpine goats, including their cross, were used in this study. The initial analyses were performed using the following single-trait random regression models (STRRM): third- and fifth-order Legendre polynomials (Leg3 and Leg5), linear B-splines with 3 and 5 knots, the Ali and Schaeffer function (Ali), and Wilmink function. Heterogeneity of residual variances was modeled considering 3 classes. After the selection of the best STRRM to describe each trait on the basis of the deviance information criterion (DIC) and posterior model probabilities (PMP), the functions were combined to compose the MTRRM. All combined MTRRM presented lower DIC values and higher PMP, showing the superiority of these models when compared to other MTRRM based only on the same function assumed for all traits. Among the combined MTRRM, those considering Ali to describe MY and PP and Leg5 to describe FP (Ali_Leg5_Ali model) presented the best fit. From the Ali_Leg5_Ali model, heritability estimates over time for MY, FP. and PP ranged from 0.25 to 0.54, 0.27 to 0.48, and 0.35 to 0.51, respectively. Genetic correlation between MY and FP, MY and PP, and FP and PP ranged from -0.58 to 0.03, -0.46 to 0.12, and 0.37 to 0.64, respectively. We concluded that combining different functions under a MTRRM approach can be a plausible alternative for joint genetic evaluation of milk yield and milk constituents in goats.

  18. Comparing and combining data across multiple sources via integration of paired-sample data to correct for measurement error.

    PubMed

    Huang, Yunda; Huang, Ying; Moodie, Zoe; Li, Sue; Self, Steve

    2012-12-10

    In biomedical research such as the development of vaccines for infectious diseases or cancer, study outcomes measured by an assay or device are often collected from multiple sources or laboratories. Measurement error that may vary between laboratories needs to be adjusted for when combining samples across data sources. We incorporate such adjustment in the main study by comparing and combining independent samples from different laboratories via integration of external data, collected on paired samples from the same two laboratories. We propose the following: (i) normalization of individual-level data from two laboratories to the same scale via the expectation of true measurements conditioning on the observed; (ii) comparison of mean assay values between two independent samples in the main study accounting for inter-source measurement error; and (iii) sample size calculations of the paired-sample study so that hypothesis testing error rates are appropriately controlled in the main study comparison. Because the goal is not to estimate the true underlying measurements but to combine data on the same scale, our proposed methods do not require that the true values for the error-prone measurements are known in the external data. Simulation results under a variety of scenarios demonstrate satisfactory finite sample performance of our proposed methods when measurement errors vary. We illustrate our methods using real enzyme-linked immunosorbent spot assay data generated by two HIV vaccine laboratories.

  19. Comparing and Combining Data across Multiple Sources via Integration of Paired-sample Data to Correct for Measurement Error

    PubMed Central

    Huang, Yunda; Huang, Ying; Moodie, Zoe; Li, Sue; Self, Steve

    2014-01-01

    Summary In biomedical research such as the development of vaccines for infectious diseases or cancer, measures from the same assay are often collected from multiple sources or laboratories. Measurement error that may vary between laboratories needs to be adjusted for when combining samples across laboratories. We incorporate such adjustment in comparing and combining independent samples from different labs via integration of external data, collected on paired samples from the same two laboratories. We propose: 1) normalization of individual level data from two laboratories to the same scale via the expectation of true measurements conditioning on the observed; 2) comparison of mean assay values between two independent samples in the Main study accounting for inter-source measurement error; and 3) sample size calculations of the paired-sample study so that hypothesis testing error rates are appropriately controlled in the Main study comparison. Because the goal is not to estimate the true underlying measurements but to combine data on the same scale, our proposed methods do not require that the true values for the errorprone measurements are known in the external data. Simulation results under a variety of scenarios demonstrate satisfactory finite sample performance of our proposed methods when measurement errors vary. We illustrate our methods using real ELISpot assay data generated by two HIV vaccine laboratories. PMID:22764070

  20. 5 CFR 591.216 - How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... combine survey data for the DC area and for COLA areas with multiple survey areas? (a) Washington, DC... DC area and for COLA areas with multiple survey areas? 591.216 Section 591.216 Administrative... DC survey areas identified in § 591.215(a) and then averages these average prices together...

  1. 5 CFR 591.216 - How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... combine survey data for the DC area and for COLA areas with multiple survey areas? (a) Washington, DC... DC area and for COLA areas with multiple survey areas? 591.216 Section 591.216 Administrative... DC survey areas identified in § 591.215(a) and then averages these average prices together...

  2. 5 CFR 591.216 - How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... combine survey data for the DC area and for COLA areas with multiple survey areas? (a) Washington, DC... DC area and for COLA areas with multiple survey areas? 591.216 Section 591.216 Administrative... DC survey areas identified in § 591.215(a) and then averages these average prices together...

  3. Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intra-luminal thrombus formation

    PubMed Central

    Biasetti, Jacopo; Hussain, Fazle; Gasser, T. Christian

    2011-01-01

    Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear–stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the λ2-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau–Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth. PMID:21471188

  4. Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intra-luminal thrombus formation.

    PubMed

    Biasetti, Jacopo; Hussain, Fazle; Gasser, T Christian

    2011-10-01

    Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear-stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the λ(2)-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau-Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.

  5. Mild depletion of dietary folate combined with other B vitamins alters multiple components of the Wnt pathway in mouse colon.

    PubMed

    Liu, Zhenhua; Choi, Sang-Woon; Crott, Jimmy W; Keyes, Mary K; Jang, Hyeran; Smith, Donald E; Kim, Myungjin; Laird, Peter W; Bronson, Roderick; Mason, Joel B

    2007-12-01

    Preclinical and clinical studies suggest that diminished folate status increases the risk of colorectal carcinogenesis. However, many biochemical functions of folate are dependent on the adequate availability of other 1-carbon nutrients, including riboflavin, vitamin B-6, and vitamin B-12. Aberrations in the Wnt pathway are thought to play an important role in human colorectal cancers. This study therefore investigated if mild depletion of folate combined with depletion of riboflavin, vitamin B-6, and vitamin B-12 could induce alterations in the Wnt pathway in the colonic mucosa. Ninety-six mice were pair-fed diets with different combinations of B vitamin depletion for 10 wk. Genomic DNA methylation and uracil misincorporation were measured by LC/MS and GC/MS. Gene-specific methylation, strand breaks, and expressions were measured by real-time PCR and immunoblotting. Proliferation and apoptosis were determined by immunohistochemistry. DNA strand breaks within the Apc mutation cluster region were induced by folate depletion combined with inadequacies of riboflavin, vitamin B-6, and vitamin B-12 (P < 0.05), but such effects were not induced by folate depletion alone. Similarly, minor changes in the expression of Apc, beta-catenin, and cyclin D1 produced by mild folate depletion were significantly magnified by multiple vitamin depletion. Apoptosis, which can be suppressed by increased Wnt-signaling, was attenuated by the combined deficiency state (P < 0.05) but not by singlet or doublet deficiencies. These findings indicate that a mild depletion of folate that is of insufficient magnitude by itself to induce alterations in components of the Wnt pathway may produce such effects when present in conjunction with mild inadequacies of other 1-carbon nutrients.

  6. Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

    PubMed

    Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

    2016-11-01

    The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated. PMID:27682899

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

    PubMed

    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.

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

    PubMed

    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. PMID:27379394

  9. Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

    PubMed

    Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

    2016-11-01

    The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.

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

    PubMed

    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.

  11. [An Elderly Patient with Multiple Lung Metastases after Colectomy Successfully Treated with a Combination Oral UFT/LV Chemotherapy Regimen].

    PubMed

    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.

  12. Combining Non Selective Gas Sensors on a Mobile Robot for Identification and Mapping of Multiple Chemical Compounds

    PubMed Central

    Victor Hernandez, Bennetts; Schaffernicht, Erik; Pomareda, Victor; Lilienthal, Achim J.; Marco, Santiago; Trincavelli, Marco

    2014-01-01

    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. PMID:25232911

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

    PubMed

    Bennetts, Victor Hernandez; Schaffernicht, Erik; Pomareda, Victor; Lilienthal, Achim J; Marco, Santiago; Trincavelli, Marco

    2014-01-01

    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. PMID:25232911

  14. Bortezomib in combination with low-dose oral melphalan, dexamethasone and thalidomide for relapsed elderly patients with multiple myeloma

    PubMed Central

    Azarm, Taleb; Akbari, Mojtaba; Azarm, Arezo; Mohager, Hamid

    2012-01-01

    BACKGROUND: The aim of the study was to assess the effects of combination of bortezomib moderate dose and continuous oral low dose melphalan and thalidomide and dexamethasone (BMTD regimen) in elderly patients aged ≥ 65 years with relapsed multiple myeloma (MM). METHODS: Twenty four patients with advanced MM were enrolled to receive eight 3-week treatment cycles with bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 followed by three 5-week cycles with bortezomib 1.3 mg/m2 on days 1, 8, 15, and 22. Within all cycles, dexamethasone 24 mg/d was given intravenously on the day of bortezomib injection and the day thereafter. In addition, patients received oral treatment of melphalan at a dose of 5 mg/d continuously for twenty days for every cycle. RESULTS: Mean age of study patients was 72.8 ± 6.4 years. All patients that completed at least one treatment cycle were evaluated for response. Complete, partial, and minor responses occurred in 19%, 65% and 6% of patients, respectively. Overall response rate was 90% (efficacy analysis). CONCLUSIONS: This study demonstrated potent in vivo activity of combination therapy with BMTD regimen in patients with relapsed MM, with an acceptable safety profile and high overall response rate. PMID:23248651

  15. Prolactin in combination with interferon-β reduces disease severity in an animal model of multiple sclerosis.

    PubMed

    Zhornitsky, Simon; Johnson, Trina A; Metz, Luanne M; Weiss, Samuel; Yong, V Wee

    2015-01-01

    Previous work has demonstrated that the hormone prolactin promotes oligodendrocyte precursor proliferation and remyelination following lysolecithin-induced demyelination of the mouse spinal cord. Prolactin, however, can elicit pro-inflammatory responses, and its use in the prototypical demyelinating and inflammatory condition, multiple sclerosis (MS), should thus be approached cautiously. Here, we sought to determine whether recombinant prolactin could alter the course of experimental autoimmune encephalomyelitis (EAE), an inflammatory animal model of MS. Consistent with previous literature, we found that prolactin activated leukocytes in vitro. Daily treatment with prolactin from around the time of onset of clinical signs, for 9 (days 9 to 17) or 25 (days 9 to 33) days did not increase clinical or histological signs of EAE over that of vehicle-treated mice. Instead, the combination of prolactin and a suboptimal dose of recombinant murine interferon-β resulted in (days 9 to 17 group) or trended towards (days 9 to 33 group), a greater amelioration of clinical signs of EAE, compared to either treatment alone or to vehicle controls. Histological analyses corroborated the clinical EAE data. These results suggest that prolactin may be beneficial when administered in combination with interferon-β in MS.

  16. Inhibition of Semliki Forest virus multiplication in L-cells by combinations of interferon and ribavirin as measured by plaque titration and direct enzyme immunoassay.

    PubMed

    Harmsen, T; Van Veenendaal, D; Kraaijeveld, C A

    1994-01-01

    Inhibition of Semliki Forest virus (SFV) multiplication in L-cell monolayers by combinations of mouse interferon (IFN) and ribavirin was measured by plaque titration and by direct enzyme immunoassay of SFV in L-cells. When critically inhibitory quantities of IFN and ribavirin were combined, an additive inhibitory effect was observed in either assay.

  17. Efficacy of monepantel and anthelmintic combinations against multiple-resistant Haemonchus contortus in sheep, including characterisation of the nematode isolate.

    PubMed

    Baker, K E; George, S D; Stein, P A; Seewald, W; Rolfe, P F; Hosking, B C

    2012-05-25

    Three experiments defined the resistance profile of a population of Haemonchus contortus, which was shown to express multiple resistances to the benzimidazole, levamisole, macrocyclic lactone and salicylanilide anthelmintic classes when given as a registered combination. Study 1 was a faecal egg count reduction (FECR) test and the efficacies for the anthelmintics were monepantel, 100%; abamectin+levamisole+oxfendazole, 40.0%; and abamectin+levamisole+oxfendazole+naphthalophos, 100%. No larvae were recovered from the post-treatment cultures for monepantel or the 4-way treatment, and for the 3-way treatment the culture was 100% Haemonchus spp. Efficacies in Study 2 were calculated from mean post-mortem nematode burdens of H. contortus and were levamisole+oxfendazole, 3.1%; abamectin+levamisole+oxfendazole, 5.0%; ivermectin, 0.4%; moxidectin, 28.4% and closantel, 70.2%. Study 3 was also a FECR test that resulted in efficacies of 100% for monepantel and 83.0% for a formulated 4-way combination of abamectin+levamisole+albendazole+closantel. Larvae recovered from the post-treatment culture for the combination-treated sheep were all Haemonchus spp. Multi-resistant parasites such as examined in these studies are a continuing challenge to be managed by farmers and their advisors. Control programs must be planned and well-managed, and should include on-farm testing for anthelmintic resistance, monitoring of nematode burdens (by FEC and larval culture) to determine appropriate treatment times and the management of pastures to reduce the overall parasite challenge. This should be in balance with the generation, use and maintenance of drug-susceptible nematode populations in refugia.

  18. [Evaluation of the tolerance and efficiency of quinfamide, a new intraluminal amebicide, in man (one day treatment). Double blind study].

    PubMed

    Guevara, L

    1980-01-01

    A new intraluminal amebicide (Quinfamide) was tested to assess its effectivity and tolerance for treatment of non-dysenteric intestinal amebiasis. The drug was administered to three groups of ten patients each, whom received 300, 600 and 1 200 mg. on a 24 hours schedule. Another group of ten patients received Teclozan as control drug. Diagnosis and results were judged by rectosigmoidoscopy before, 15 and 30 days after treatment. In addition, microscopic investigation of ameba was performed in freshly passed stools, before, and after 8, 15 and 30 days of treatment. Success after treatment with the three doses of Quinfamide was obtained in 89.2% of the cases. Side reactions were clinically non-significant. More experience is needed before the effectivity of the drug is stablished.

  19. Intraluminal occlusion of the seminal duct by laser and Histoacryl: Two non-invasive alternatives for vasectomy

    NASA Astrophysics Data System (ADS)

    Freitag, B.; Sroka, R.; Koelle, S.; Becker, A. J.; Khoder, W.; Pongratz, T.; Stief, C. G.; Trottmann, M.

    2014-03-01

    Introduction and objective: Vasectomy is a well-established method in family control. Even though it is a safe and low risk operation, this surgery is invasive and difficult to reverse. Therefore the aim of this study was to investigate new non-invasive methods for occlusion of the seminal duct. Material and Methods: Seminal duct tissue was obtained from patients (n=30) suffering from prostate cancer and therefore undergoing prostatectomy. In a first set of experiments, the seminal duct was occluded by intraluminal application of Histoacryl® (Braun Aesculap AG, Tuttlingen, Germany). In a 2nd set of experiments, endoluminal laser induced occlusion was performed. Four different laser wavelengths (1940nm, 1470nm, 1064nm, 940nm) and different sets of laser parameters (e.g. power, exposure duration, fibre diameter, energy applied) were compared. Effectiveness of occlusion of the seminal duct was proven by post-treatment irrigation flow measurement, as well as by morphological analyses. To evaluate a potential damage of the surrounding tissue, external temperature was measured using a thermometer during laser application. Results: Intraluminal application of Histoacryl® induced an immediate and complete occlusion of the seminal duct. The underlying connective tissue maintained its functional integrity after this treatment. By laser light application to a Histoacryl® block, a hole could be created into the block thus indicating the possibility of recanalization. Treatment with laser energy resulted in shrinkage of the ductal lumen. The laser application generally caused necrosis in the epithelium and induced formation of vacuoles in the underlying connective tissue. As described for endoluminal varicose treatment, this distinct local reaction might result in an intense inflammation leading to a functional occlusion of the vas deferens. Conclusions: Both laser-induced occlusion and application of Histoacryl® are fast and simple techniques which may be able to achieve a

  20. Parabolic relationship between plasma triacylglycerols and LDL-cholesterol in familial combined hyperlipidaemia: the multiple-type hyperlipidaemia explained?

    PubMed

    Brouwers, Martijn C G J; de Graaf, Jacqueline; van Greevenbroek, Marleen M J; Georgieva, Anna M; van der Kallen, Carla J H; Ter Avest, Ewoud; Stehouwer, Coen D A; Stalenhoef, Anton F; de Bruin, Tjerk W A

    2008-03-01

    FCHL (familial combined hyperlipidaemia) is a highly prevalent genetic lipid disorder that accounts for a substantial number of premature cardiovascular events. To date, FCHL has been complicated by the different lipid phenotypes that are present within one family and one individual patient over time. In the present study, we hypothesized that a parabolic relationship between plasma triacylglycerols (triglycerides) and LDL (low-density lipoprotein)-cholesterol can explain this so-called 'multiple-type hyperlipidaemia' in FCHL. Our hypothesis was tested in two well-documented FCHL cohorts [Maastricht (n=145) and Nijmegen (n=299)] that were followed over a 5-year interval. Three groups were constructed depending on plasma triacylglycerols: group A (individuals with both measurements below 1.5 mmol/l), group B (one measurement below and one measurement above 1.5 mmol/l) and group C (both measurement above 1.5 mmol/l). In both male, but not female, cohorts, a significant positive relationship between plasma triacylglycerols and LDL-cholesterol was observed in group A (P=0.02 for Maastricht cohort and P=0.001 for the Nijmegen cohort), a significant negative relationship in group C (P=0.01 for Maastricht cohort and P=0.02 for the Nijmegen cohort), and a relationship intermediate to group A and C in group B. In contrast, both apoB (apolipoprotein B) levels and the prevalence of cardiovascular disease were related with plasma triacylglycerols in a more linear fashion. In conclusion, a parabolic relationship between plasma triacylglycerols and LDL-cholesterol explains the 'multiple-type hyperlipidaemia' in FCHL. In addition, the linear relationship between triacylglycerols and both apoB levels and the prevalence of cardiovascular disease substantiate the use of apoB instead of LDL-cholesterol in the diagnosis of FCHL and the prediction of cardiovascular disease.

  1. Measuring the impact of the computer on the consultation: an open source application to combine multiple observational outputs.

    PubMed

    Pflug, Bernhar; Kumarapeli, Pushpa; van Vlymen, Jeremy; Ammenwerth, Elske; de Lusignan, Simon

    2010-01-01

    A diverse range of tools and techniques can be used to observe the clinical consultation and the use of information technology. These technologies range from transcripts; to video observation with one or more cameras; to voice and pattern recognition applications. Currently, these have to be observed separately and there is limited capacity to combine them. Consequently, when multiple methods are used to analyse the consultation a significant proportion of time is spent linking events in one log file (e.g. mouse movements and keyboard use when prescribing alerts appear) with what was happening in the consultation at that time. The objective of this study was to develop an application capable of combining and comparing activity log-files and with facilities to view simultaneously all data relating to any time point or activity. Interviews, observations and design prototypes were used to develop a specification. Class diagram of the application design was used to make further development decisions. The application development used object-orientated design principles. We used open source tools; Java as the programming language and JDeveloper as the development environment. The final output is log file aggregation (LFA) tool which forms part of the wider aggregation of log files for analysis (ALFA) open source toolkit ( www.biomedicalinformatics.info/alfa/ ). Testing was done using sample log files and reviewed the application's utility for analysis of the consultation activities. Separation of the presentation and functionality in the design stage enabled us to develop a modular and extensible application. The application is capable of converting and aggregating several log files of different formats and displays them in different presentation layouts. We used the Java Media Framework to aggregate video channels. Java extensible mark-up language (XML) package facilitated the conversion of aggregated output into XML format. Analysts can now move easily between

  2. Combining multiple FDG-PET radiotherapy target segmentation methods to reduce the effect of variable performance of individual segmentation methods

    SciTech Connect

    McGurk, Ross J.; Bowsher, James; Das, Shiva K.; Lee, John A

    2013-04-15

    different between 128 Multiplication-Sign 128 and 256 Multiplication-Sign 256 grid sizes for either method (MJV, p= 0.0519; STAPLE, p= 0.5672) but was for SMASD values (MJV, p < 0.0001; STAPLE, p= 0.0164). The best individual method varied depending on object characteristics. However, both MJV and STAPLE provided essentially equivalent accuracy to using the best independent method in every situation, with mean differences in DSC of 0.01-0.03, and 0.05-0.12 mm for SMASD. Conclusions: Combining segmentations offers a robust approach to object segmentation in PET. Both MJV and STAPLE improved accuracy and were robust against the widely varying performance of individual segmentation methods. Differences between MJV and STAPLE are such that either offers good performance when combining volumes. Neither method requires a training dataset but MJV is simpler to interpret, easy to implement and fast.

  3. Combining multiple fallout radionuclides (137Cs, 7Be, 210Pbxs) improves our understanding of sediment source dynamics in tropical rivers

    NASA Astrophysics Data System (ADS)

    Evrard, O.; Laceby, J. P.; Huon, S.; Lefèvre, I.; Sengtaheuanghoung, O.; Ribolzi, O.

    2015-12-01

    Soil erosion has accelerated as a result of land use change, increasing the sediment supply to rivers worldwide. A thorough knowledge of sediment dynamics is required to design efficient management measures to control erosion and reduce sediment delivery from catchments. Fallout radionuclides are often used separately to provide spatial (137Cs) or temporal (7Be, 210Pbxs) information on sediment sources. In this study, we examine their combined application to simultaneously model spatial and temporal sediment source dynamics. To this end, potential sediment sources (n=84) and suspended sediment (n=16) were collected at two stations in a 12 km² catchment in Northern Laos during the first flood of the 2014 wet season. Part of the source material was directly sampled in ephemeral flow occurring on hillslopes to avoid the grain size selectivity problems that may occur during erosion and river transport processes. A distribution modelling approach quantified the relative contributions of recently eroded surface (labelled with both 7Be and 137Cs), recently eroded subsurface (depleted in both 7Be and 137Cs), re-suspended surface (depleted in 7Be and labelled with 137Cs) and re-suspended subsurface sources (enriched in 7Be and depleted in 137Cs). At an upstream sampling location, surface sources contributed the majority of sediment (55%) whereas subsurface sources dominated the supply of sediment downstream (74%). Importantly, re-suspended subsurface sources, labelled with 7Be, were a significant sediment source at the catchment outlet (60%). This approach demonstrates the utility of combining multiple radionuclides when investigating spatial and temporal sediment source dynamics in tropical catchments. In the future, sampling of source material in ephemeral flows occurring on hillslopes should be encouraged. Furthermore, the proposed approach should be tested in larger catchments to guide the implementation of efficient erosion control measures.

  4. Combined treatment with the mood stabilizers lithium and valproate produces multiple beneficial effects in transgenic mouse models of Huntington's disease.

    PubMed

    Chiu, Chi-Tso; Liu, Guangping; Leeds, Peter; Chuang, De-Maw

    2011-11-01

    Emerging evidence suggests that the mood stabilizers lithium and valproate (VPA) have broad neuroprotective and neurotrophic properties, and that these occur via inhibition of glycogen synthase kinase 3 (GSK-3) and histone deacetylases (HDACs), respectively. Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by impaired movement, cognitive and psychiatric disturbances, and premature death. We treated N171-82Q and YAC128 mice, two mouse models of HD varying in genetic backgrounds and pathological progressions, with a diet containing therapeutic doses of lithium, VPA, or both. Untreated, these transgenic mice displayed a decrease in levels of GSK-3β serine 9 phosphorylation and histone H3 acetylation in the striatum and cerebral cortex around the onset of behavioral deficits, indicating a hyperactivity of GSK-3β and HDACs. Using multiple well-validated behavioral tests, we found that co-treatment with lithium and VPA more effectively alleviated spontaneous locomotor deficits and depressive-like behaviors in both models of HD mice. Furthermore, compared with monotherapy with either drug alone, co-treatment more successfully improved motor skill learning and coordination in N171-82Q mice, and suppressed anxiety-like behaviors in YAC128 mice. This combined treatment consistently inhibited GSK-3β and HDACs, and caused a sustained elevation in striatal as well as cortical brain-derived neurotrophic factor and heat shock protein 70. Importantly, co-treatment markedly prolonged median survival of N171-82Q mice from 31.6 to 41.6 weeks. Given that there is presently no proven treatment for HD, our results suggest that combined treatment with lithium and VPA, two mood stabilizers with a long history of safe use in humans, may have important therapeutic potential for HD patients.

  5. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    PubMed

    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.

  6. Discounting of monetary rewards that are both delayed and probabilistic: delay and probability combine multiplicatively, not additively.

    PubMed

    Vanderveldt, Ariana; Green, Leonard; Myerson, Joel

    2015-01-01

    The value of an outcome is affected both by the delay until its receipt (delay discounting) and by the likelihood of its receipt (probability discounting). Despite being well-described by the same hyperboloid function, delay and probability discounting involve fundamentally different processes, as revealed, for example, by the differential effects of reward amount. Previous research has focused on the discounting of delayed and probabilistic rewards separately, with little research examining more complex situations in which rewards are both delayed and probabilistic. In 2 experiments, participants made choices between smaller rewards that were both immediate and certain and larger rewards that were both delayed and probabilistic. Analyses revealed significant interactions between delay and probability factors inconsistent with an additive model. In contrast, a hyperboloid discounting model in which delay and probability were combined multiplicatively provided an excellent fit to the data. These results suggest that the hyperboloid is a good descriptor of decision making in complicated monetary choice situations like those people encounter in everyday life.

  7. The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma.

    PubMed

    García-Sanz, R; González-Porras, J R; Hernández, J M; Polo-Zarzuela, M; Sureda, A; Barrenetxea, C; Palomera, L; López, R; Grande-García, C; Alegre, A; Vargas-Pabón, M; Gutiérrez, O N; Rodríguez, J A; San Miguel, J F

    2004-04-01

    We evaluate the efficacy of the oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) in 71 refractory/relapsed multiple myeloma patients, including a prognostic analysis to predict both response and survival. Patients received thalidomide at escalating doses (200-800 mg/day), daily cyclophosphamide (50 mg/day) and pulsed dexamethasone (40 mg/day, 4 days every 3 weeks). On an intention-to-treat basis and using the EBMT response criteria, 2% patients reached complete response (CR), 55% partial response (PR) and 26% minor response (MR) yielding a total response (CR+PR+MR) rate of 83% after 3 months of therapy. After 6 months of therapy, responses were maintained including a 10% CR. The 2-year progression free and overall survival were 57 and 66%, respectively. A favorable response was associated with beta2 microglobulin < or =4 mg/dl, platelets >80 x 10(9)/l and nonrefractory disease. Regarding survival, low beta2 microglobulin (< or =4 mg/dl), age (< or =65 years) and absence of extramedullary myelomatous lesion were associated with a longer survival. Major adverse effects included constipation (24%), somnolence (18%), fatigue (17%) and infection (13%). Only 7% of patients developed a thrombo-embolic event. ThaCyDex is an oral regimen that induces a high response rate and long remissions, particularly in relapsing patients with beta2 microglobulin < or =4 mg/dl and < or =65 years. PMID:14973508

  8. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    PubMed

    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. PMID:26985781

  9. Discounting of Monetary Rewards that are Both Delayed and Probabilistic: Delay and Probability Combine Multiplicatively, not Additively

    PubMed Central

    Vanderveldt, Ariana; Green, Leonard; Myerson, Joel

    2014-01-01

    The value of an outcome is affected both by the delay until its receipt (delay discounting) and by the likelihood of its receipt (probability discounting). Despite being well-described by the same hyperboloid function, delay and probability discounting involve fundamentally different processes, as revealed, for example, by the differential effects of reward amount. Previous research has focused on the discounting of delayed and probabilistic rewards separately, with little research examining more complex situations in which rewards are both delayed and probabilistic. In two experiments, participants made choices between smaller rewards that were both immediate and certain and larger rewards that were both delayed and probabilistic. Analyses revealed significant interactions between delay and probability factors inconsistent with an additive model. In contrast, a hyperboloid discounting model in which delay and probability were combined multiplicatively provided an excellent fit to the data. These results suggest that the hyperboloid is a good descriptor of decision making in complicated monetary choice situations like those people encounter in everyday life. PMID:24933696

  10. Composition dependent multiple structural transformations of myoglobin in aqueous ethanol solution: A combined experimental and theoretical study

    SciTech Connect

    Ghosh, R.; Samajdar, R. N.; Bhattacharyya, Aninda Jiban; Bagchi, B.

    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.

  11. Multiple trait model combining random regressions for daily feed intake with single measured performance traits of growing pigs

    PubMed Central

    Schnyder, Urs; Hofer, Andreas; Labroue, Florence; Künzi, Niklaus

    2002-01-01

    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. PMID:11929625

  12. Multiple trait model combining random regressions for daily feed intake with single measured performance traits of growing pigs.

    PubMed

    Schnyder, Urs; Hofer, Andreas; Labroue, Florence; Künzi, Niklaus

    2002-01-01

    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 1449 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 describe 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 550000 rounds each, from which 50000 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.

  13. Composition dependent multiple structural transformations of myoglobin in aqueous ethanol solution: A combined experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    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.

  14. Barcoding against a paradox? Combined molecular species delineations reveal multiple cryptic lineages in elusive meiofaunal sea slugs

    PubMed Central

    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

  15. Combining multiple data sources for the quantification of snow and glacier melt contributions to streamflow over the last 100 years

    NASA Astrophysics Data System (ADS)

    Stahl, Kerstin; Freudiger, Daphné S.; Kohn, Irene; Seibert, Jan; Weiler, Markus

    2015-04-01

    High alpine headwater catchments are important source areas for many large rivers. There is considerable interest in understanding and predicting the changing hydrological processes in these catchments due to climatic changes. At the same time, high elevation regions tend to be data scarce. The aim of the study is a re-analysis of the changing contributions of snow and glacier melt to streamflow in the river Rhine over the entire 20th Century. The success of quantifying these contributions across scales and over such a long time period depends on the use of all available information. We present the challenges and benefits of combining multiple regional data sources (i) to analyze these changes empirically and (ii) to constrain hydrological modeling in the headwater basins. The reconstruction of gridded meteorological variables for the period 1901-1950 based on an analogue resampling technique created a consistent meteorological forcing over the entire period. Glacier extents from maps of the early 20th Century defined the starting conditions to bridge the time to existing glacier volume and area change data. The analysis of the co-variability and trends in a set of long time series of climate variables and streamflow in unregulated headwaters provided insight into different phases of changing climate-hydrology relations. These signatures, together with the snow water equivalent maps for the last 30 years produced by the SLF and the collection of all available streamflow records provided important benchmarks for model calibration and validation. This work improves the understanding of climate sensitivity in high mountain environments and demonstrates important challenges when modeling partly compensating effects of a changing climate.

  16. Wall stress in media layer of stented three-layered aortic aneurysm at different intraluminal thrombus locations with pulsatile heart cycle.

    PubMed

    Rahmani, Shahrokh; Alagheband, Mohammad; Karimi, Alireza; Alizadeh, Mansour; Navidbakhsh, Mahdi

    2015-05-01

    At the point when the aorta ruptures suddenly, as opposed to as the after-effect of injury, it is for the most part in aortic aneurysm. Aortic aneurysm rupture happens when the wall stress surpasses the strength of the vascular tissue. Intraluminal thrombus (ILT) may have advantages as it can absorb tension and decrease aortic aneurysm wall stress. This study aims to investigate the presence and growth effects of ILT on the wall stress in a stented aneurysm in one heart cycle. A virtual stented aneurysm model with ILT was made to study the flow and wall dynamics using fluid-structure interaction (FSI) analysis. Wall stresses at the center line of media layer of aorta thickness were calculated by two-dimensional axisymmetric finite element analysis. Calculations were executed as thrombus elastic modulus increased from 0.1 to 2 MPa and calculations were repeated as thrombus depth was increased in 10% increment until thrombus filled the whole aneurysm cavity. The von Mises stresses were compared in three sections, namely proximal, aneurysm and distal sections in the abdominal aorta. The wall stress showed its maximum value during a peak flow and pressure and gradually decreased as the pressure and velocity of blood reduced in all three aforementioned sections. As the intraluminal thrombus depth increased from 10% to 100%, the wall stress in distal, proximal and centre of aneurysm during one heart cycle was decreased. Furthermore, increasing the elastic modulus of thrombus from 10% to 100% triggered a reduction in wall stress in proximal, centre of intraluminal thrombus and distal regions during one heart cycle. The achievements of this study may have implications not only for understanding the wall stress in ILT, but also for providing more detailed information about aortic aneurysm with intraluminal thrombus and can help surgeons to do their best.

  17. A Hybrid Chalcone Combining the Trimethoxyphenyl and Isatinyl Groups Targets Multiple Oncogenic Proteins and Pathways in Hepatocellular Carcinoma Cells

    PubMed Central

    Cao, Lili; Zhang, Lijun; Zhao, Xiang; Zhang, Ye

    2016-01-01

    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. PMID:27525972

  18. A Hybrid Chalcone Combining the Trimethoxyphenyl and Isatinyl Groups Targets Multiple Oncogenic Proteins and Pathways in Hepatocellular Carcinoma Cells.

    PubMed

    Cao, Lili; Zhang, Lijun; Zhao, Xiang; Zhang, Ye

    2016-01-01

    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. PMID:27525972

  19. Vitamin B12 absorption--a study of intraluminal events in control subjects and patients with tropical sprue.

    PubMed Central

    Kapadia, C R; Bhat, P; Jacob, E; Baker, S J

    1975-01-01

    The intraluminal fate of orally administered radioactive vitamin B12 has been studied in control subjects with normal vitamin B12 absorption and those with vitamin B12 malabsorption due to tropical sprue. In control subjects 1 to 21% of the dose was bound to sedimentable material and 37 to 75% was bound to immunoreactive intrinsic factor. In subjects with vitamin B12 malabsorption due to tropical sprue, the results were identical with the control subjects. Bacteriological studies showed a statistically significant correlation between both the number of flora in the jejunum and the number of bacteroides in both the jejunum and ileum and vitamin B12 malabsorption. In patients with tropical sprue who have normal intrinsic factor secretion, the vitamin B12 absorptive defect is not due to binding of the vitamin to bacteria or to alteration to the intrinsic factor vitamin B12 complex in the intestinal lumen. The lesion appears to be one of the mucosal cell receptors or of the cells themselves, possibly caused by bacterial toxins. PMID:3457

  20. An Integrated Fluid-Chemical Model Toward Modeling the Formation of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms

    PubMed Central

    Biasetti, Jacopo; Spazzini, Pier Giorgio; Swedenborg, Jesper; Gasser, T. Christian

    2012-01-01

    Abdominal Aortic Aneurysms (AAAs) are frequently characterized by the presence of an Intra-Luminal Thrombus (ILT) known to influence their evolution biochemically and biomechanically. The ILT progression mechanism is still unclear and little is known regarding the impact of the chemical species transported by blood flow on this mechanism. Chemical agonists and antagonists of platelets activation, aggregation, and adhesion and the proteins involved in the coagulation cascade (CC) may play an important role in ILT development. Starting from this assumption, the evolution of chemical species involved in the CC, their relation to coherent vortical structures (VSs) and their possible effect on ILT evolution have been studied. To this end a fluid-chemical model that simulates the CC through a series of convection-diffusion-reaction (CDR) equations has been developed. The model involves plasma-phase and surface-bound enzymes and zymogens, and includes both plasma-phase and membrane-phase reactions. Blood is modeled as a non-Newtonian incompressible fluid. VSs convect thrombin in the domain and lead to the high concentration observed in the distal portion of the AAA. This finding is in line with the clinical observations showing that the thickest ILT is usually seen in the distal AAA region. The proposed model, due to its ability to couple the fluid and chemical domains, provides an integrated mechanochemical picture that potentially could help unveil mechanisms of ILT formation and development. PMID:22934022

  1. Long-term assessment of motor and cognitive behaviours in the intraluminal perforation model of subarachnoid hemorrhage in rats.

    PubMed

    Silasi, Gergely; Colbourne, Frederick

    2009-03-17

    The endovascular perforation model of subarachnoid hemorrhage (SAH) is a commonly used model in rats as it is performed without a craniotomy and accurately mimics the physiological effects of SAH in humans. The long-term behavioural profile of the model, however, has not been characterized. Given that humans often have cognitive deficits following SAH, we set out to characterize the behavioural profile as well as the spontaneous temperature changes of rats following intraluminal perforation. Rats were pre-trained on three motor tasks (tapered beam, limb-use asymmetry and the horizontal ladder tasks) prior to receiving a SAH. The animals were then assessed on post-surgical days 3, 7, 14 and 21 on these tasks. At the completion of motor testing, the rats were assessed on a moving platform version of the Morris water task. Despite significant mortality (33%), SAH did not result in lasting motor deficits on any of the tasks examined. However, the SAH group did show a minor cognitive impairment in the Morris water task. In addition, SAH produced a slight, but significant elevation in body temperature (vs. sham operated rats) despite an acute decrease in general home cage activity. The majority of the animals did not have any observable infarcts and the SAH did not significantly affect cortical thickness. In summary, the endovascular perforation model of SAH results in no lasting motor deficits and only minor cognitive impairment in survivors, which alone would be difficult to evaluate in neuroprotection or rehabilitation studies. PMID:19059287

  2. Role of altered esophageal intraluminal baseline impedance levels in patients with gatroesophageal reflux disease refractory to proton pump inhibitors.

    PubMed

    Jiang, Liuqin; Ye, Bixing; Lin, Lin; Wang, Ying; Wang, Meifeng

    2016-08-01

    Numerous studies have investigated utility of esophageal intraluminal baseline impedance levels (BILs) in gastroesophageal reflux disease (GERD). However, effect of BILs in refractory GERD (RGERD) has not been well investigated. The aim of this study is to evaluate role of BILs in RGERD patients. Total 62 subjects with refractory gastroesophageal reflux symptoms underwent 24-hour impedance-pH monitoring and gastroendoscopy. Distal BILs in acid reflux type were significantly lower than those in nonacid reflux type and functional heartburn (FH) group. Distal BILs of reflux esophagitis (RE) patients were lower than those of nonerosive reflux disease (NERD) patients, while there were no statistical significance between 2 groups. Patients with severe esophagitis had lower distal BILs than those with mild esophagitis and NERD patients, and patients with severe esophagitis in acid reflux type had the lowest distal BILs. Distal BILs were significantly negatively correlated with DeMeester score, episodes of acid reflux, and acid exposure time, but no correlated with episodes of nonacid reflux. Characteristics of BILs in RGERD patients were similar with those in GERD patients, but might be more complicated. Evaluating BILs in RGERD patients could achieve a better understanding of pathophysiology in RGERD. PMID:27537561

  3. Exploring multiple feature combination strategies with a recurrent neural network architecture for off-line handwriting recognition

    NASA Astrophysics Data System (ADS)

    Mioulet, L.; Bideault, G.; Chatelain, C.; Paquet, T.; Brunessaux, S.

    2015-01-01

    The BLSTM-CTC is a novel recurrent neural network architecture that has outperformed previous state of the art algorithms in tasks such as speech recognition or handwriting recognition. It has the ability to process long term dependencies in temporal signals in order to label unsegmented data. This paper describes different ways of combining features using a BLSTM-CTC architecture. Not only do we explore the low level combination (feature space combination) but we also explore high level combination (decoding combination) and mid-level (internal system representation combination). The results are compared on the RIMES word database. Our results show that the low level combination works best, thanks to the powerful data modeling of the LSTM neurons.

  4. An instrument for combining x-ray multiple diffraction and x-ray topographic imaging for examining crystal microcrystallography and perfection

    SciTech Connect

    Lai, X.; Ma, C. Y.; Roberts, K. J.; Cardoso, L. P.; Santos, A. O. dos; Bogg, D.; Miller, M. C.

    2009-03-15

    Diffraction imaging using x-ray topography (XRT) and x-ray multiple diffraction (XRMD) provide valuable tools for examining the growth defects in crystals and the distributions from ideal lattice symmetry (microcrystallography). The topographic x-ray multiple diffraction microprobe (TMDM) combines the complementary aspects of both techniques enabling XRT and XRMD studies within the same instrument providing a useful resource for the structural characterization of materials that are not very stable in vacuum and electron beam environments. The design of the TMDM instrument is described together with data taken on GaAs (001) and potassium dihydrogen phosphate (001)

  5. Combined exercise training reduces IFN-γ and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis.

    PubMed

    Golzari, Zahra; Shabkhiz, Fatemeh; Soudi, Sara; Kordi, Mohammad Reza; Hashemi, Seyed Mahmoud

    2010-11-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder in which lymphocytic infiltration mediated mainly by pro-inflammatory cytokines. In this study, we examined the effect of combined exercise training on the levels of IFN-γ, IL-4 and IL-17 in the plasma and the supernatant of peripheral blood lymphocytes in women with multiple sclerosis. Expanded Disability Status Scale (EDSS), VO(2)max, muscle strength, and balance tests were obtained at baseline and post-treatment follow-up. Combined exercises training was designed for 24 sessions during 8 weeks. Each session was started with 5 min warm-up and was followed by 10 min stretch training, 20 min aerobic exercises and 20 min resistance-endurance training. The disability score was significantly decreased in test MS subjects after 8 weeks combined exercise training. Muscle strength and balance were increased significantly after the training program in test group. In this study, plasma, and peripheral blood mononuclear cell (PBMC) IL-17 and IFN-γ production was significantly decreased after 8 weeks combined training. Our findings suggest that combined training has useful anti-inflammatory effects by decrease in PBMC and plasma IL-17 production. PMID:20797460

  6. Multiple Channel Exposure Therapy: Combining Cognitive-Behavioral Therapies for the Treatment of Posttraumatic Stress Disorder with Panic Attacks

    ERIC Educational Resources Information Center

    Falsetti, Sherry A.; Resnick, Heidi S.; Davis, Joanne

    2005-01-01

    A large proportion of patients who present for treatment of posttraumatic stress disorder (PTSD) experience comorbid panic attacks, yet it is unclear to what extent currently available PTSD treatment programs address this problem. Here we describe a newly developed treatment, multiple-channel exposure therapy (M-CET), for comorbid PTSD and panic…

  7. [Complete response to CPT-11 and UFT/LV combination therapy in a case with simultaneous multiple lung metastases from colon cancer].

    PubMed

    Ishida, Hideyuki; Akita, Hirofumi; Watanabe, Yasunori; Nakaguchi, Kazunori; Kabuto, Toshiyuki

    2006-06-01

    We report the complete response for one year of a patient with simultaneous multiple lung metastases from colon cancer who was treated using a combination of irinotecan (CPT-11) and uracil/tegafur (UFT)/Leucovorin (LV) using a schedule reported overseas. A 61-year-old woman was admitted to our hospital and diagnosed with ascending colon cancer and simultaneous multiple lung metastases. The patient underwent a right hemicolectomy and was treated with CPT-11 (150 mg/m(2)) on day 1 and oral UFT and oral LV on days 1-14. This treatment cycle was repeated every 3 weeks. A CT examination after 4 cycles of chemotherapy revealed a partial response of multiple lung metastases, and the next examination after 6 cycles revealed a complete response. The adverse effects observed during this chemotherapy regimen were leucopenia (grade 1), neutropenia (grade 2), vomiting (grade 2) and hair loss (grade 1). The patient is now receiving her 22nd cycle of chemotherapy, and her multiple metastases have shown a complete response for one year. The CPT-11 and UFT/LV combination therapy was well tolerated and was covered by the national health insurance system in Japan. This treatment may enable prolonged survival and improve quality of life in patients with metastatic colorectal cancer.

  8. Circumferential targeted renal sympathetic nerve denervation with preservation of the renal arterial wall using intra-luminal ultrasound

    NASA Astrophysics Data System (ADS)

    Roth, Austin; Coleman, Leslie; Sakakura, Kenichi; Ladich, Elena; Virmani, Renu

    2015-03-01

    An intra-luminal ultrasound catheter system (ReCor Medical's Paradise System) has been developed to provide circumferential denervation of the renal sympathetic nerves, while preserving the renal arterial intimal and medial layers, in order to treat hypertension. The Paradise System features a cylindrical non-focused ultrasound transducer centered within a balloon that circulates cooling fluid and that outputs a uniform circumferential energy pattern designed to ablate tissues located 1-6 mm from the arterial wall and protect tissues within 1 mm. RF power and cooling flow rate are controlled by the Paradise Generator which can energize transducers in the 8.5-9.5 MHz frequency range. Computer simulations and tissue-mimicking phantom models were used to develop the proper power, cooling flow rate and sonication duration settings to provide consistent tissue ablation for renal arteries ranging from 5-8 mm in diameter. The modulation of these three parameters allows for control over the near-field (border of lesion closest to arterial wall) and far-field (border of lesion farthest from arterial wall, consisting of the adventitial and peri-adventitial spaces) depths of the tissue lesion formed by the absorption of ultrasonic energy and conduction of heat. Porcine studies have confirmed the safety (protected intimal and medial layers) and effectiveness (ablation of 1-6 mm region) of the system and provided near-field and far-field depth data to correlate with bench and computer simulation models. The safety and effectiveness of the Paradise System, developed through computer model, bench and in vivo studies, has been demonstrated in human clinical studies.

  9. Combination bortezomib and rituximab treatment affects multiple survival and death pathways to promote apoptosis in mantle cell lymphoma

    PubMed Central

    Alinari, Lapo; White, Valerie L; Earl, Christian T; Ryan, Timothy P; Johnston, Jeffrey S; Dalton, James T; Ferketich, Amy K; Lai, Raymond; Lucas, David M; Porcu, Pierluigi; Blum, Kristie A; Byrd, John C

    2009-01-01

    Mantle cell lymphoma (MCL) is a distinct histologic subtype of B cell non-Hodgkins lymphoma (NHL) associated with an aggressive clinical course. Inhibition of the ubiquitin-proteasome pathway modulates survival and proliferation signals in MCL and has shown clinical benefit in this disease. This has provided rationale for exploring combination regimens with B-cell selective immunotherapies such as rituximab. In this study, we examined the effects of combined treatment with bortezomib and rituximab on patient-derived MCL cell lines (Jeko, Mino, SP53) and tumor samples from patients with MCL where we validate reversible proteasome inhibition concurrent with cell cycle arrest and additive induction of apoptosis. When MCL cells were exposed to single agent bortezomib or combination bortezomib/rituximab, caspase dependent and independent apoptosis was observed. Single agent bortezomib or rituximab treatment of Mino and Jeko cell lines and patient samples resulted in decreased levels of nuclear NFκB complex(es) capable of binding p65 consensus oligonucleotides, and this decrease was enhanced by the combination. Constitutive activation of the Akt pathway was also diminished with bortezomib alone or in combination with rituximab. On the basis of in vitro data demonstrating additive apoptosis and enhanced NFκB and phosphorylated Akt depletion in MCL with combination bortezomib plus rituximab, a phase II trial of bortezomib-rituximab in patients with relapsed/refractory MCL is underway. PMID:20046572

  10. Slip regulation for anti-lock braking systems using multiple surface sliding controller combined with inertial delay control

    NASA Astrophysics Data System (ADS)

    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.

  11. Parametric and exergetic analysis of a two-stage transcritical combined organic Rankine cycle used for multiple grades waste heat recovery of diesel engine

    NASA Astrophysics Data System (ADS)

    Tian, H.; Zhang, J.; Xu, X. F.; Shu, G. Q.; Wei, H. Q.

    2013-12-01

    Diesel engine has multiple grades of waste heat with different ratios of combustion heat, exhaust is 400 °C with the ratio of 21% and coolant is 90 °C with 19%. Few previous publications investigate the recovery of multiple grades waste heat together. In this paper, a two-stage transcritical combined organic rankine cycle (CORC) is presented and analyzed. In the combined system, the high and low temperature stages transcritical cycle recover the high grades waste heat, and medium to low grades waste heat respectively, and being combined efficiently. Meanwhile, the suitable working fluids for high stage are chosen and analyzed. The cycle parameters, including thermal efficiency (ηth), net power output (Pnet), energy efficiency (ηexg) and global thermal efficiency of DE-CORC(ηglo) have also been analyzed and optimized. The results indicate that this combined system could recover all the waste heat with a high recovery ratio (above 90%) and obtain a maximum power output of 37kW for a DE of 243kW. The global thermal efficiency of DE-CORC can get a max value of 46.2% compared with 40% for single DE. The results also indicate that all the energy conversion process have a high exergy efficiency.

  12. A Combined Multiple-SLED Broadband Light Source at 1300 nm for High Resolution Optical Coherence Tomography

    PubMed Central

    Wang, Hui; Jenkins, Michael W.; Rollins, Andrew M.

    2013-01-01

    We demonstrate a compact, inexpensive, and reliable fiber–coupled light source with broad bandwidth and sufficient power at 1300 nm for high resolution optical coherence tomography (OCT) imaging in real-time applications. By combining four superluminescent diodes (SLEDs) with different central wavelengths, the light source has a bandwidth of 145 nm centered at 1325 nm with over 10 mW of power. OCT images of an excised stage 30 embryonic chick heart acquired with our combined SLED light source (<5 μm axial resolution in tissue) are compared with images obtained with a single SLED source (~10 μm axial resolution in tissue). The high resolution OCT system with the combined SLED light source provides better image quality (smaller speckle noise) and a greater ability to observe fine structures in the embryonic heart. PMID:24347689

  13. A Combined Multiple-SLED Broadband Light Source at 1300 nm for High Resolution Optical Coherence Tomography.

    PubMed

    Wang, Hui; Jenkins, Michael W; Rollins, Andrew M

    2008-04-01

    We demonstrate a compact, inexpensive, and reliable fiber-coupled light source with broad bandwidth and sufficient power at 1300 nm for high resolution optical coherence tomography (OCT) imaging in real-time applications. By combining four superluminescent diodes (SLEDs) with different central wavelengths, the light source has a bandwidth of 145 nm centered at 1325 nm with over 10 mW of power. OCT images of an excised stage 30 embryonic chick heart acquired with our combined SLED light source (<5 μm axial resolution in tissue) are compared with images obtained with a single SLED source (~10 μm axial resolution in tissue). The high resolution OCT system with the combined SLED light source provides better image quality (smaller speckle noise) and a greater ability to observe fine structures in the embryonic heart.

  14. [Long-term complete response of multiple lung metastases from renal cell carcinoma induced by combination therapy with interferon alpha and UFT: a case report].

    PubMed

    Terachi, T; Okada, Y; Takeuchi, H; Yoshida, O

    1993-04-01

    We report a case of long-term complete response of multiple lung metastases of renal cell carcinoma (RCC) by the combination therapy with interferon alpha (IFN alpha) and UFT. A 38 year-old man having left RCC with lung metastases underwent radical left nephrectomy and extended lymph node dissection, the pathological stage being pT2N2. Although metastatic lung tumors increased in size and number against intravenously admitted interferon gamma (IFN gamma) therapy after the surgery, they completely disappeared following the subsequent combination therapy with intramuscularly admitted interferon alpha (IFN alpha) and oral intake of UFT in about 2 years. The patient has been disease-free for 5 years after cessation of the treatment. Combination therapy with IFN alpha and UFT might be more effective on metastases of RCC than single use of IFN alpha or IFN gamma.

  15. Combining Multiple Types of Motor Rehabilitation Enhances Skilled Forelimb Use Following Experimental Traumatic Brain Injury in Rats

    PubMed Central

    Adkins, DeAnna L.; Ferguson, Lindsay; Lance, Steven; Pevtsov, Aleksandr; McDonough, Kevin; Stamschror, Justin; Jones, Theresa A.; Kozlowski, Dorothy A.

    2016-01-01

    Background Neuroplasticity and neurorehabilitation have been extensively studied in animal models of stroke to guide clinical rehabilitation of stroke patients. Similar studies focused on traumatic brain injury (TBI) are lacking. Objective The current study was designed to examine the effects of individual and combined rehabilitative approaches, previously shown to be beneficial following stroke, in an animal model of moderate/severe TBI, the controlled cortical impact (CCI). Methods Rats received a unilateral CCI, followed by reach training, voluntary exercise, or unimpaired forelimb constraint, alone or in combination. Forelimb function was assessed at different time points post-CCI by tests of skilled reaching, motor coordination, and asymmetrical limb use. Results Following CCI, skilled reaching and motor coordination were significantly enhanced by combinations of rehabilitation strategies, not by individual approaches. The return of symmetrical limb use benefited from forelimb constraint alone. None of the rehabilitation strategies affected the size of injury, suggesting that enhanced behavioral function was not a result of neuroprotection. Conclusions The current study has provided evidence that individual rehabilitation strategies shown to be beneficial in animal models of stroke are not similarly sufficient to enhance behavioral outcome in a model of TBI. Motor rehabilitation strategies for TBI patients may need to be more intense and varied. Future basic science studies exploring the underlying mechanisms of combined rehabilitation approaches in TBI as well as clinical studies comparing rehabilitation approaches for stroke versus TBI would prove fruitful. PMID:25761884

  16. Combining Multiple-Module Output Boundary Conditions to Produce a Single-Input-Module Boundary Condition in FRAMES

    SciTech Connect

    Whelan, Gene; Castleton, Karl J.; Buck, John W.; Taira, Randal Y.; Gelston, Gariann M.; Strenge, Dennis L.

    2006-10-03

    The Plus Operator thus provides a mechanism to group modules of similar output so that the output can be combined and supplied to downstream modules. This document provides requirements, the design, data-file specifications, the test plan, and the quality assurance/quality control (QA/QC) protocol for the Plus Operator.

  17. Quantal release of Ca2+ from intracellular stores by InsP3: tests of the concept of control of Ca2+ release by intraluminal Ca2+.

    PubMed

    Tregear, R T; Dawson, A P; Irvine, R F

    1991-03-22

    A possible mechanism for the generation of 'quantal' release of intracellular Ca2+ by InsP3 (Muallem et al., J. biol. Chem. 264, 205-212 (1989)) has been put forward in which intraluminal Ca2+ levels modulate InsP3 receptor structure (Irvine, FEBS Lett. 263, 5-9 (1990)). Here we have modelled such a steady-state mechanism, with an InsP3-sensitive store plus an InsP3-insensitive one, to test its ability to mimic published data. We have also performed experiments on InsP3-stimulated rat liver microsomes to test whether the model is consistent with one-way Ca2+ fluxes at a steady state. The model can simulate quantal release, in that InsP3 produces a release of part of the stored Ca2+ which is initially rapid relative to the one-way flux. In the original form of the model, in which InsP3-modulated Ca2+ binding to the intraluminal site opens the Ca2+ channel, the range of InsP3 concentrations needed to release Ca2+ is greater than that observed. When the model is changed so that Ca2(+)-modulated InsP3 binding opens the channels, the effective InsP3 range is shortened, but the quantal release effect is reduced. Other published data on one-way fluxes, and our own data on microsomes, can be simulated when leakage from the InsP3-insensitive store is adjusted to fit the observations; these data therefore do not test the existence of a steady state in the InsP3-sensitive store. We conclude that sensitivity of Ca2+ release to intraluminal Ca2+ provides a steady-state explanation of most, but not all, current quantal release observations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1675803

  18. Multiple Olefin Metathesis Polymerization That Combines All Three Olefin Metathesis Transformations: Ring-Opening, Ring-Closing, and Cross Metathesis.

    PubMed

    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. PMID:26185967

  19. Multiple Olefin Metathesis Polymerization That Combines All Three Olefin Metathesis Transformations: Ring-Opening, Ring-Closing, and Cross Metathesis.

    PubMed

    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. [Model of intraluminal perfusion of the guinea pig ileum in vitro in the study of the antidiarrheal properties of the guava (Psidium guajava)].

    PubMed

    Lozoya, X; Becerril, G; Martínez, M

    1990-01-01

    An experimental in vitro model was developed for the study of plant extracts reported by traditional medicines in the treatment of diarrhea. The guinea-pig isolated ileum is perfused with the plant extract using an intraluminal approach. The peristaltic reflex is induced by electrical stimulation while the plant extract is perfused. The spasmolytic effects of Psidium guajava leaf methanol, hexane and water extracts were demonstrated suggesting the existence of two different types of active components. The results obtained allow to propose this in vitro method as a useful model to reproduce some of the characteristics of the oral way of administration of plant extracts.

  1. Influence of cytokinins in combination with GA₃ on shoot multiplication and elongation of tea clone Iran 100 (Camellia sinensis (L.) O. Kuntze).

    PubMed

    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.

  2. Influence of Cytokinins in Combination with GA3 on Shoot Multiplication and Elongation of Tea Clone Iran 100 (Camellia sinensis (L.) O. Kuntze)

    PubMed Central

    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

  3. Influence of cytokinins in combination with GA₃ on shoot multiplication and elongation of tea clone Iran 100 (Camellia sinensis (L.) O. Kuntze).

    PubMed

    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. PMID:24605069

  4. Combination of nucleic acid and protein isolation with tissue array construction: using defined histologic regions in single frozen tissue blocks for multiple research purposes.

    PubMed

    Li, Hong; Sun, Yuan; Kong, Qing-You; Zhang, Kai-Li; Wang, Xiao-Wei; Chen, Xiao-Yan; Wang, Qian; Liu, Jia

    2003-09-01

    Precise dissection of defined histological regions for nucleic acid and protein isolation is a precedent step in finding out cancer-related alterations, and high quality tissue microarrays are demanded in the validation of screened genetic alterations by multiple in situ approaches. In this study, a combined technique was developed by which sample isolation and tissue array construction could be performed on the defined morphological region(s) in single tissue block. The RNA and protein samples generated from the selected portions were of good quality and sufficient for multiple experimental purposes. The frozen tissue arrays constructed on a novel recipient are suitable for multiple in situ evaluations including immunohistochemical staining and mRNA hybridisation. In most cases, the data obtained from in situ assays coincided well with the ones revealed by RT-PCR and Western blot hybridisation. The potential experimental bias caused by cell contamination can be amended by tissue array-based retrospective examination. The combination of tissue-selective sample preparations with tissue array construction thus provide a tool by which comprehensive cancer research can be performed on defined histological regions in a series of single frozen tissue blocks.

  5. A phase 1, open-label, dose-escalation study of pralatrexate in combination with bortezomib in patients with relapsed/refractory multiple myeloma.

    PubMed

    Dunn, Tamara J; Dinner, Shira; Price, Elizabeth; Coutré, Steven E; Gotlib, Jason; Hao, Ying; Berube, Caroline; Medeiros, Bruno C; Liedtke, Michaela

    2016-04-01

    Pralatrexate inhibits folic acid metabolism, and preclinical studies have shown that it is cytotoxic to multiple myeloma cells. This phase 1 study investigated the safety and efficacy of pralatrexate in combination with bortezomib in adults with relapsed or refractory multiple myeloma. A standard 3 + 3 design was used. Patients received intravenous pralatrexate at doses ranging from 10 to 30 mg/m(2) and intravenous bortezomib at a dose of 1·3 mg/m(2) on days 1, 8 and 15 of each 4-week cycle. Eleven patients were enrolled and completed a median of two cycles. The maximum tolerated dose was 20 mg/m(2) . Two patients experienced dose-limiting toxicity of mucositis. The most frequent non-haematological toxicities were fatigue (55%) and mucositis (45%). There were three serious adverse events in three patients: rash, sepsis and hypotension. One patient (9%) had a very good partial response, 1 (9%) had a partial response, 1 (9%) had minimal response and two (18%) had progressive disease. The median duration of response was 4 months, the median time to next treatment was 3·4 months and the median time to progression was 4 months. Pralatrexate, in combination with bortezomib, was generally safe and demonstrated modest activity in relapsed or refractory multiple myeloma. Clinicaltrials.gov identifier: NCT01114282.

  6. Suppression of large intraluminal bubble expansion in shock wave lithotripsy without compromising stone comminution: Methodology and in vitro experiments

    NASA Astrophysics Data System (ADS)

    Zhong, Pei; Zhou, Yufeng

    2001-12-01

    To reduce the potential of vascular injury without compromising the stone comminution capability of a Dornier HM-3 lithotripter, we have devised a method to suppress intraluminal bubble expansion via in situ pulse superposition. A thin shell ellipsoidal reflector insert was designed and fabricated to fit snugly into the original reflector of an HM-3 lithotripter. The inner surface of the reflector insert shares the same first focus with the original HM-3 reflector, but has its second focus located 5 mm proximal to the generator than that of the HM-3 reflector. With this modification, the original lithotripter shock wave is partitioned into a leading lithotripter pulse (peak positive pressure of 46 MPa and positive pulse duration of 1 μs at 24 kV) and an ensuing second compressive wave of 10 MPa peak pressure and 2 μs pulse duration, separated from each other by about 4 μs. Superposition of the two waves leads to a selective truncation of the trailing tensile component of the lithotripter shock wave, and consequently, a reduction in the maximum bubble expansion up to 41% compared to that produced by the original reflector. The pulse amplitude and -6 dB beam width of the leading lithotripter shock wave from the upgraded reflector at 24 kV are comparable to that produced by the original HM-3 reflector at 20 kV. At the lithotripter focus, while only about 30 shocks are needed to cause a rupture of a blood vessel phantom made of cellulose hollow fiber (i.d.=0.2 mm) using the original HM-3 reflector at 20 kV, no rupture could be produced after 200 shocks using the upgraded reflector at 24 kV. On the other hand, after 100 shocks the upgraded reflector at 24 kV can achieve a stone comminution efficiency of 22%, which is better than the 18% efficiency produced by the original reflector at 20 kV (p=0.043). All together, it has been shown in vitro that the upgraded reflector can produce satisfactory stone comminution while significantly reducing the potential for vessel

  7. Combination of spatial diversity and parallel decision feedback equalizer in a Single Input Multiple Output underwater acoustic communication system operating at very high frequencies

    NASA Astrophysics Data System (ADS)

    Skoro Kaskarovska, Violeta; Beaujean, Pierre-Philippe

    2013-05-01

    Single Input Multiple Output (SIMO) acoustic communication system using an adaptive spatial diversity combined with parallel Decision Feedback Equalizer (DFE) is presented in this document. The SIMO system operates at high frequencies with high data rate over a limited range (less than 200 m) in very shallow waters. The SIMO system consists of a single source transmitting Phase Shift Keying (PSK) messages modulated at 300 kHz and received by multiple receivers. In a first configuration, the symbols collected at each receiver are equalized using a decision feedback equalizer and combined using Maximum Ratio Combining (MRC). In a second configuration, the MRC outputs are used as decision symbols in the DFE. This second configuration is a form of turbo equalization: the process can be repeated over and over, leading to a better estimate of the received message as the number of iterations increases. The adaptive process of diversity is repeated until the best possible result is achieved or a predefined error criterion is met. Bit Error Rate (BER) and Signal-to-Noise-and-Interference Ratio (SNIR) are used as performance metrics of the acoustic channel. Experimental results using SIMO system with three, four or five receivers and pre-processed real recorded data demonstrate ability to improve the performance of the acoustic channel in challenging environments. Using received messages with non-zero BER, adaptive spatial diversity can achieve BER of 0% and increased SNIR of 3 dB with number of iterations depending on the number of receivers used.

  8. Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations.

    PubMed

    Lopez, Aurelio; Mateos, Maria-Victoria; Oriol, Albert; Valero, Marta; Martínez, Joaquín; Lorenzo, Jose Ignacio; Perez, Montserrat; Martinez, Rafael; de Paz, Raquel; Granell, Miguel; De Arriba, Felipe; Blanchard, M Jesús; Peñalver, Francisco Javier; Bello, Jose Luis; Martin, Maria Luisa; Bargay, Joan; Blade, Joan; Lahuerta, Juan Jose; San Miguel, Jesús F; de la Rubia, Javier

    2015-01-01

    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). PMID:26500850

  9. An application of combining results from multiple methods—statistical evaluation of uncertainty for NIST SRM 1508a

    NASA Astrophysics Data System (ADS)

    Hornikova, A.; Zhang, N. F.; Welch, M. J.; Tai, S.

    2006-06-01

    NIST standard reference materials (SRMs) are certified reference materials that are developed at NIST and provided to laboratories (industry, government and academia) for assessment and improvement of measurement quality. This paper details the statistical analysis related to the recertification of SRM 1508a, benzoylecgonine (cocaine metabolite) in freeze-dried urine, to incorporate new data. The recertification is based on combining measurement results from different measurement methods and time periods. Several different statistical models and corresponding estimators were considered for the certified value, its standard uncertainty and its expanded uncertainty.

  10. Risk Assessment and Prediction of Flyrock Distance by Combined Multiple Regression Analysis and Monte Carlo Simulation of Quarry Blasting

    NASA Astrophysics Data System (ADS)

    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.

  11. Evaluation of a glycoengineered monoclonal antibody via LC-MS analysis in combination with multiple enzymatic digestion

    PubMed Central

    Liu, Renpeng; Giddens, John; McClung, Colleen M.; Magnelli, Paula E.; Wang, Lai-Xi; Guthrie, Ellen P.

    2016-01-01

    ABSTRACT Glycosylation affects the efficacy, safety and pharmacokinetics/pharmacodynamics properties of therapeutic monoclonal antibodies (mAbs), and glycoengineering is now being used to produce mAbs with improved efficacy. In this work, a glycoengineered version of rituximab was produced by chemoenzymatic modification to generate human-like N-glycosylation with α 2,6 linked sialic acid. This modified rituximab was comprehensively characterized by liquid chromatography-mass spectrometry and compared to commercially available rituximab. As anticipated, the majority of N-glycans were converted to α 2,6 linked sialic acid, in contrast to CHO-produced rituximab, which only contains α 2,3 linked sialic acid. Typical posttranslational modifications, such as pyro-glutamic acid formation at the N-terminus, oxidation at methionine, deamidation at asparagine, and disulfide linkages were also characterized in both the commercial and glycoengineered mAbs using multiple enzymatic digestion and mass spectrometric analysis. The comparative study reveals that the glycoengineering approach does not cause any additional posttranslational modifications in the antibody except the specific transformation of the glycoforms, demonstrating the mildness and efficiency of the chemoenzymatic approach for glycoengineering of therapeutic antibodies. PMID:26514686

  12. Root of the Eukaryota tree as inferred from combined maximum likelihood analyses of multiple molecular sequence data.

    PubMed

    Arisue, Nobuko; Hasegawa, Masami; Hashimoto, Tetsuo

    2005-03-01

    Extensive studies aiming to establish the structure and root of the Eukaryota tree by phylogenetic analyses of molecular sequences have thus far not resulted in a generally accepted tree. To re-examine the eukaryotic phylogeny using alternative genes, and to obtain a more robust inference for the root of the tree as well as the relationship among major eukaryotic groups, we sequenced the genes encoding isoleucyl-tRNA and valyl-tRNA synthetases, cytosolic-type heat shock protein 90, and the largest subunit of RNA polymerase II from several protists. Combined maximum likelihood analyses of 22 protein-coding genes including the above four genes clearly demonstrated that Diplomonadida and Parabasala shared a common ancestor in the rooted tree of Eukaryota, but only when the fast-evolving sites were excluded from the original data sets. The combined analyses, together with recent findings on the distribution of a fused dihydrofolate reductase-thymidylate synthetase gene, narrowed the possible position of the root of the Eukaryota tree on the branch leading to Opisthokonta or to the common ancestor of Diplomonadida/Parabasala. However, the analyses did not agree with the position of the root located on the common ancestor of Opisthokonta and Amoebozoa, which was argued by Stechmann and Cavalier-Smith [Curr. Biol. 13:R665-666, 2003] based on the presence or absence of a three-gene fusion of the pyrimidine biosynthetic pathway: carbamoyl-phosphate synthetase II, dihydroorotase, and aspartate carbamoyltransferase. The presence of the three-gene fusion recently found in the Cyanidioschyzon merolae (Rhodophyta) genome sequence data supported our analyses against the Stechmann and Cavalier-Smith-rooting in 2003.

  13. The combined use of photoaffinity labeling and surface plasmon resonance-based technology identifies multiple salicylic acid-binding proteins.

    PubMed

    Tian, Miaoying; von Dahl, Caroline C; Liu, Po-Pu; Friso, Giulia; van Wijk, Klaas J; Klessig, Daniel F

    2012-12-01

    Salicylic acid (SA) is a small phenolic molecule that not only is the active ingredient in the multi-functional drug aspirin, but also serves as a plant hormone that affects diverse processes during growth, development, responses to abiotic stresses and disease resistance. Although a number of SA-binding proteins (SABPs) have been identified, the underlying mechanisms of action of SA remain largely unknown. Efforts to identify additional SA targets, and thereby elucidate the complex SA signaling network in plants, have been hindered by the lack of effective approaches. Here, we report two sensitive approaches that utilize SA analogs in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology to identify and evaluate candidate SABPs from Arabidopsis. Using these approaches, multiple proteins, including the E2 subunit of α-ketoglutarate dehydrogenase and the glutathione S-transferases GSTF2, GSTF8, GSTF10 and GSTF11, were identified as SABPs. Their association with SA was further substantiated by the ability of SA to inhibit their enzymatic activity. The photoaffinity labeling and surface plasmon resonance-based approaches appear to be more sensitive than the traditional approach for identifying plant SABPs using size-exclusion chromatography with radiolabeled SA, as these proteins exhibited little to no SA-binding activity in such an assay. The development of these approaches therefore complements conventional techniques and helps dissect the SA signaling network in plants, and may also help elucidate the mechanisms through which SA acts as a multi-functional drug in mammalian systems.

  14. Mechanisms underlying muscle fatigue differ between multiple sclerosis patients and controls: a combined electrophysiological and neuroimaging study.

    PubMed

    Steens, A; Heersema, D J; Maurits, N M; Renken, R J; Zijdewind, I

    2012-02-15

    Increased sense of fatigue is an important and conspicuous symptom in multiple sclerosis (MS). Muscle fatigue is associated with increased sense of fatigue in MS (Steens et al., 2011). The aim of this study was to investigate mechanisms that can explain muscle fatigue in MS patients and controls. We assessed changes in cortical activation (BOLD), voluntary activation (twitch interpolation) and muscle force during a sustained maximal voluntary contraction (MVC) in twenty MS patients and twenty healthy controls. In control participants, individual differences in force decline (mean 65% MVC, 8 SD) during the sustained maximal contraction could be accounted for by differences in maximal voluntary force (R(2): 0.49, p = 0.001); stronger participants presented a larger force decline. The small decline in voluntary activation (mean 7.8%, 11.8 SD) did not contribute significantly to the force decline. During the sustained contraction, the force decline was accompanied by an increase in cortical activation in the main motor areas. In MS patients, the differences in the decline in force (mean 67% MVC, 9 SD) were significantly associated (R(2): 0.51, p = 0.001) with a decline in voluntary activation (mean 20.1%, 20.6 SD) and not with maximal force or decline in rest twitch. The corresponding cortical activation in motor areas showed an increase in the first two intervals of the sustained contraction but declined during the last interval. Our data indicate that muscle fatigue during a sustained contraction in MS patients is associated with changes in the voluntary activation that are not sufficiently compensated by increased cortical activation. Control participants, however, show increased cortical activation to compensate for these fatigue-related changes in voluntary activation and the major cause of force decline is therefore to be found in the periphery (muscles).

  15. A novel Bruton's tyrosine kinase inhibitor CC-292 in combination with the proteasome inhibitor carfilzomib impacts the bone microenvironment in a multiple myeloma model with resultant antimyeloma activity.

    PubMed

    Eda, H; Santo, L; Cirstea, D D; Yee, A J; Scullen, T A; Nemani, N; Mishima, Y; Waterman, P R; Arastu-Kapur, S; Evans, E; Singh, J; Kirk, C J; Westlin, W F; Raje, N S

    2014-09-01

    Bruton's tyrosine kinase (Btk) modulates B-cell development and activation and has an important role in antibody production. Interestingly, Btk may also affect human osteoclast (OC) function; however, the mechanism was unknown. Here we studied a potent and specific Btk inhibitor, CC-292, in multiple myeloma (MM). In this report, we demonstrate that, although CC-292 increased OC differentiation, it inhibited OC function via inhibition of c-Src, Pyk2 and cortactin, all involved in OC-sealing zone formation. As CC-292 did not show potent in vitro anti-MM activity, we next evaluated it in combination with the proteasome inhibitor, carfilzomib. We first studied the effect of carfilzomib on OC. Carfilzomib did not have an impact on OC-sealing zone formation but significantly inhibited OC differentiation. CC-292 combined with carfilzomib inhibited both sealing zone formation and OC differentiation, resulting in more profound inhibition of OC function than carfilzomib alone. Moreover, the combination treatment in an in vivo MM mouse model inhibited tumor burden compared with CC-292 alone; it also increased bone volume compared with carfilzomib alone. These results suggest that CC-292 combined with carfilzomib augments the inhibitory effects against OC within the bone microenvironment and has promising therapeutic potential for the treatment of MM and related bone disease.

  16. Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma.

    PubMed

    Matthews, G M; Lefebure, M; Doyle, M A; Shortt, J; Ellul, J; Chesi, M; Banks, K M; Vidacs, E; Faulkner, D; Atadja, P; Bergsagel, P L; Johnstone, R W

    2013-09-12

    Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinostat, romidepsin) and novel combination therapies using in vitro human MM cell lines and in vivo preclinical screening utilizing syngeneic transplanted Vk*MYC MM. HDACi were combined with ABT-737, which targets the intrinsic apoptosis pathway, recombinant human tumour necrosis factor-related apoptosis-inducing ligand (rhTRAIL/MD5-1), that activates the extrinsic apoptosis pathway or the DNA methyl transferase inhibitor 5-azacytidine. We demonstrate that in vitro cell line-based studies provide some insight into drug activity and combination therapies that synergistically kill MM cells; however, they do not always predict in vivo preclinical efficacy or toxicity. Importantly, utilizing transplanted Vk*MYC MM, we report that panobinostat and 5-azacytidine synergize to prolong the survival of tumor-bearing mice. In contrast, combined HDACi/rhTRAIL-based strategies, while efficacious, demonstrated on-target dose-limiting toxicities that precluded prolonged treatment. Taken together, our studies provide evidence that the transplanted Vk*MYC model of MM is a useful screening tool for anti-MM drugs and should aid in the prioritization of novel drug testing in the clinic.

  17. A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial

    PubMed Central

    Sangelaji, Bahram; Kordi, Mohammadreza; Banihashemi, Farzaneh; Nabavi, Seyed Massood; Khodadadeh, Sara; Dastoorpoor, Maryam

    2016-01-01

    Background: Multiple sclerosis (MS) is a neurological disease with a variety of signs and symptoms. Exercise therapy has been shown to improve physical functions in MS. However, questions about an optimal exercise therapy remain. In this regard, we suggest a combined exercise therapy including aerobic and resistance exercises for MS patients. The study is designed to observe, test and compare the effects of proposed combined exercises on strength, balance, agility, fatigue, speed, and walking distance in people with mild to moderate MS [0 < expanded disability status scale (EDSS) < 5]. Methods: A total of 40 people with relapse-remitting MS (16 male, 0 < EDSS < 5) were randomized into one of the four groups (3 intervention and one control). The intervention consisted of various combinations of aerobic and resistance exercises with different repetition rates. Pre- and post-intervention scores of fatigue severity scale (FSS), timed up and go (TUG) test, 6-minute walk test (6MWT), 10- and 20-MWT, Berg balance scale (BBS), and one repetition maximum (1RM) test were recorded and analyzed. Results: For most tests, post-intervention values of the group 1, with 3-aerobic and 1-resistance exercises, were significantly higher compared to control group (P < 0.050). However, no significant progression was observed in the other two intervention groups. Conclusion: A combination of three aerobic exercises with one resistance exercise may result in improved balance, locomotion, and endurance in MS patients. PMID:27648171

  18. A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial

    PubMed Central

    Sangelaji, Bahram; Kordi, Mohammadreza; Banihashemi, Farzaneh; Nabavi, Seyed Massood; Khodadadeh, Sara; Dastoorpoor, Maryam

    2016-01-01

    Background: Multiple sclerosis (MS) is a neurological disease with a variety of signs and symptoms. Exercise therapy has been shown to improve physical functions in MS. However, questions about an optimal exercise therapy remain. In this regard, we suggest a combined exercise therapy including aerobic and resistance exercises for MS patients. The study is designed to observe, test and compare the effects of proposed combined exercises on strength, balance, agility, fatigue, speed, and walking distance in people with mild to moderate MS [0 < expanded disability status scale (EDSS) < 5]. Methods: A total of 40 people with relapse-remitting MS (16 male, 0 < EDSS < 5) were randomized into one of the four groups (3 intervention and one control). The intervention consisted of various combinations of aerobic and resistance exercises with different repetition rates. Pre- and post-intervention scores of fatigue severity scale (FSS), timed up and go (TUG) test, 6-minute walk test (6MWT), 10- and 20-MWT, Berg balance scale (BBS), and one repetition maximum (1RM) test were recorded and analyzed. Results: For most tests, post-intervention values of the group 1, with 3-aerobic and 1-resistance exercises, were significantly higher compared to control group (P < 0.050). However, no significant progression was observed in the other two intervention groups. Conclusion: A combination of three aerobic exercises with one resistance exercise may result in improved balance, locomotion, and endurance in MS patients.

  19. S-SAD phasing of monoclinic histidine kinase from Brucella abortus combining data from multiple crystals and orientations: an example of data-collection strategy and a posteriori analysis of different data combinations.

    PubMed

    Klinke, Sebastián; Foos, Nicolas; Rinaldi, Jimena J; Paris, Gastón; Goldbaum, Fernando A; Legrand, Pierre; Guimarães, Beatriz G; Thompson, Andrew

    2015-07-01

    The histidine kinase (HK) domain belonging to the light-oxygen-voltage histidine kinase (LOV-HK) from Brucella abortus is a member of the HWE family, for which no structural information is available, and has low sequence identity (20%) to the closest HK present in the PDB. The `off-edge' S-SAD method in macromolecular X-ray crystallography was used to solve the structure of the HK domain from LOV-HK at low resolution from crystals in a low-symmetry space group (P21) and with four copies in the asymmetric unit (∼108 kDa). Data were collected both from multiple crystals (diffraction limit varying from 2.90 to 3.25 Å) and from multiple orientations of the same crystal, using the κ-geometry goniostat on SOLEIL beamline PROXIMA 1, to obtain `true redundancy'. Data from three different crystals were combined for structure determination. An optimized HK construct bearing a shorter cloning artifact yielded crystals that diffracted X-rays to 2.51 Å resolution and that were used for final refinement of the model. Moreover, a thorough a posteriori analysis using several different combinations of data sets allowed us to investigate the impact of the data-collection strategy on the success of the structure determination.

  20. Metabolite identification of the antimalarial piperaquine in vivo using liquid chromatography-high-resolution mass spectrometry in combination with multiple data-mining tools in tandem.

    PubMed

    Yang, Aijuan; Zang, Meitong; Liu, Huixiang; Fan, Peihong; Xing, Jie

    2016-08-01

    Artemisinin-based combination therapy is widely used for the treatment of uncomplicated Plasmodium falciparum malaria, and piperaquine (PQ) is one of important partner drugs. The pharmacokinetics of PQ is characterized by a low clearance and a large volume of distribution; however, metabolism of PQ has not been thoroughly investigated. In this work, the metabolite profiling of PQ in human and rat was studied using liquid chromatography tandem high-resolution LTQ-Orbitrap mass spectrometry (HRMS). The biological samples were pretreated by solid-phase extraction. Data processes were carried out using multiple data-mining techniques in tandem, i.e., isotope pattern filter followed by mass defect filter. A total of six metabolites (M1-M6) were identified for PQ in human (plasma and urine) and rat (plasma, urine and bile). Three reported metabolites were also found in this study, which included N-oxidation (M1, M2) and carboxylic products (M3). The subsequent N-oxidation of M3 resulted in a new metabolite M4 detected in urine and bile samples. A new metabolic pathway N-dealkylation was found for PQ in human and rat, leading to two new metabolites (M5 and M6). This study demonstrated that LC-HRMS(n) in combination with multiple data-mining techniques in tandem can be a valuable analytical strategy for rapid metabolite profiling of drugs. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26821381

  1. An efficient technique for estimating the two-dimensional temperature distributions around multiple cryo-surgical probes based on combining contributions of unit circles.

    PubMed

    Magalov, Zaur; Shitzer, Avraham; Degani, David

    2016-10-01

    This study presents an efficient, fast and accurate method for estimating the two-dimensional temperature distributions around multiple cryo-surgical probes. The identical probes are inserted into the same depth and are operated simultaneously and uniformly. The first step in this method involves numerical derivation of the temporal performance data of a single probe, embedded in a semi-infinite, tissue-like medium. The results of this derivation are approximated by algebraic expressions that form the basis for computing the temperature distributions of multiple embedded probes by combining the data of a single probe. Comparison of isothermal contours derived by this method to those computed numerically for a variety of geometrical cases, up to 15 inserted probes and 2-10 min times of operation, yielded excellent results. Since this technique obviates the solution of the differential equations of multiple probes, the computational time required for a particular case is several orders of magnitude shorter than that needed for obtaining the full numerical solution. Blood perfusion and metabolic heat generation rates are demonstrated to inhibit the advancement of isothermal fronts. Application of this method will significantly shorten computational times without compromising the accuracy of the results. It may also facilitate expeditious consideration of the advantages of different modes of operation and the number of inserted probes at the early design stage.

  2. Analysis of the probability of multiple taxa in a combined sample of Swartkrans and Kromdraai dental material.

    PubMed

    Fuller, K

    1996-11-01

    It has been argued (Grine, [1988] Evolutionary History of the "Robust" Australopithecines [New York. Aldine de Gruyter], pp. 223-243) that the australopithecine material from Swartkrans and Kromdraai represents distinct species. In an attempt to test the validity of separate taxa at Swartkrans and Kromdraai, Cope's (Cope [1989] Systematic Variation in Cercopithecus Dental Samples [Austin: University of Texas]) method of analysis was adapted and utilized. This procedure includes an analysis of the coefficients of variation (CVs) of the individual posterior teeth (buccal-lingual breadth) of a combined fossil sample compared with the CVs of several known single taxon reference groups. The Cope and Lacy (Cope and Lacy [1992] Am. J. Phys. Anthropol. 89:359-378) stimulation technique was also employed in the analysis. Based on these analyses, there is no justification for a taxonomic separation between the australopithecine material from Swartkrans and Kromdraai. Therefore, the assertion that the Swartkrans and Kromdraai material represent two distinct species is not indicated by the available dental metric evidence. PMID:8922186

  3. Combining multiple dynamic models and deep learning architectures for tracking the left ventricle endocardium in ultrasound data.

    PubMed

    Carneiro, Gustavo; Nascimento, Jacinto C

    2013-11-01

    We present a new statistical pattern recognition approach for the problem of left ventricle endocardium tracking in ultrasound data. The problem is formulated as a sequential importance resampling algorithm such that the expected segmentation of the current time step is estimated based on the appearance, shape, and motion models that take into account all previous and current images and previous segmentation contours produced by the method. The new appearance and shape models decouple the affine and nonrigid segmentations of the left ventricle to reduce the running time complexity. The proposed motion model combines the systole and diastole motion patterns and an observation distribution built by a deep neural network. The functionality of our approach is evaluated using a dataset of diseased cases containing 16 sequences and another dataset of normal cases comprised of four sequences, where both sets present long axis views of the left ventricle. Using a training set comprised of diseased and healthy cases, we show that our approach produces more accurate results than current state-of-the-art endocardium tracking methods in two test sequences from healthy subjects. Using three test sequences containing different types of cardiopathies, we show that our method correlates well with interuser statistics produced by four cardiologists.

  4. Doppler Impedance Changes at the Fetal Brain Vessels in a Pregnancy Affected with a Multiple Combination of Uteroplacental Anomalies

    PubMed Central

    Morales-Roselló, José; Peralta Llorens, Núria

    2012-01-01

    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. PMID:22481947

  5. Combined biosynthetic pathway for de novo production of UDP-galactose: catalysis with multiple enzymes immobilized on agarose beads.

    PubMed

    Liu, Ziye; Zhang, Jianbo; Chen, Xi; Wang, Peng G

    2002-04-01

    Regeneration of sugar nucleotides is a critical step in the biosynthetic pathway for the formation of oligosaccharides. To alleviate the difficulties in the production of sugar nucleotides, we have developed a method to produce uridine diphosphate galactose (UDP-galactose). The combined biosynthetic pathway, which involves seven enzymes, is composed of three parts: i) the main pathway to form UDP-galactose from galactose, with the enzymes galactokinase, galactose-1-phosphate uridyltransferase, UDP-glucose pyrophosphorylase, and inorganic pyrophosphatase, ii) the uridine triphosphate supply pathway catalyzed by uridine monophosphate (UMP) kinase and nucleotide diphosphate kinase, and iii) the adenosine triphosphate (ATP) regeneration pathway catalyzed by polyphosphate kinase with polyphosphate added as an energy resource. All of the enzymes were expressed individually and immobilized through their hexahistidine tags onto nickel agarose beads ("super beads"). The reaction requires a stoichiometric amount of UMP and galactose, and catalytic amounts of ATP and glucose 1-phosphate, all inexpensive starting materials. After continuous circulation of the reaction mixture through the super-bead column for 48 h, 50 % of the UMP was converted into UDP-galactose. The results show that de novo production of UDP-galactose on the super-bead column is more efficient than in solution because of the stability of the immobilized enzymes.

  6. VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma.

    PubMed

    Pineda-Roman, M; Zangari, M; van Rhee, F; Anaissie, E; Szymonifka, J; Hoering, A; Petty, N; Crowley, J; Shaughnessy, J; Epstein, J; Barlogie, B

    2008-07-01

    Bortezomib (V) was combined with thalidomide (T) and dexamethasone (D) in a phase I/II trial to determine dose-limiting toxicities (DLT's) and clinical activity of the VTD regimen in 85 patients with advanced and refractory myeloma. The starting dose of V was 1.0 mg/m(2) (days 1, 4, 8, 11, every 21 day) with T added from cycle 2 at 50 mg/day, with 50 mg increments per 10 patient cohorts, to a maximum dose of 200 mg. In the absence of DLT's, the same reiteration of T dose increases was applied with a higher dose of V=1.3 mg/m(2). D was added with cycle 4 in the absence of partial response (PR). Ninety-two percent had prior autotransplants, 74% had prior T and 76% abnormal cytogenetics. MTD was reached at V=1.3 mg/m(2) and T=150 mg. Minor response (MR) was recorded in 79%, and 63% achieved PR including 22% who qualified for near-complete remission. At 4 years, 6% remain event-free and 23% alive. Both OS and EFS were significantly longer in the absence of prior T exposure and when at least MR status was attained. The MMSET/FGFR3 molecular subtype was prognostically favorable, a finding since reported for a VTD-incorporating tandem transplant trial (Total Therapy 3) for untreated patients with myeloma (BJH 2008).

  7. Combining information from two data sources with misreporting and incompleteness to assess hospice-use among cancer patients: a multiple imputation approach.

    PubMed

    He, Yulei; Landrum, Mary Beth; Zaslavsky, Alan M

    2014-09-20

    Combining information from multiple data sources can enhance estimates of health-related measures by using one source to supply information that is lacking in another, assuming the former has accurate and complete data. However, there is little research conducted on combining methods when each source might be imperfect, for example, subject to measurement errors and/or missing data. In a multisite study of hospice-use by late-stage cancer patients, this variable was available from patients' abstracted medical records, which may be considerably underreported because of incomplete acquisition of these records. Therefore, data for Medicare-eligible patients were supplemented with their Medicare claims that contained information on hospice-use, which may also be subject to underreporting yet to a lesser degree. In addition, both sources suffered from missing data because of unit nonresponse from medical record abstraction and sample undercoverage for Medicare claims. We treat the true hospice-use status from these patients as a latent variable and propose to multiply impute it using information from both data sources, borrowing the strength from each. We characterize the complete-data model as a product of an 'outcome' model for the probability of hospice-use and a 'reporting' model for the probability of underreporting from both sources, adjusting for other covariates. Assuming the reports of hospice-use from both sources are missing at random and the underreporting are conditionally independent, we develop a Bayesian multiple imputation algorithm and conduct multiple imputation analyses of patient hospice-use in demographic and clinical subgroups. The proposed approach yields more sensible results than alternative methods in our example. Our model is also related to dual system estimation in population censuses and dual exposure assessment in epidemiology.

  8. Combining information from two data sources with misreporting and incompleteness to assess hospice-use among cancer patients: a multiple imputation approach

    PubMed Central

    He, Yulei; Landrum, Mary Beth; Zaslavsky, Alan M.

    2014-01-01

    Combining information from multiple data sources can enhance estimates of health-related measures by using one source to supply information that is lacking in another, assuming the former has accurate and complete data. However, there is little research conducted on combining methods when each source might be imperfect, for example, subject to measurement errors and/or missing data. In a multisite study of hospice-use by late-stage cancer patients, this variable was available from patients’ abstracted medical records, which may be considerably underreported because of incomplete acquisition of these records. Therefore, data for Medicare-eligible patients were supplemented with their Medicare claims that contained information on hospice-use, which may also be subject to underreporting yet to a lesser degree. In addition, both sources suffered from missing data because of unit nonresponse from medical record abstraction and sample undercoverage for Medicare claims. We treat the true hospice-use status from these patients as a latent variable and propose to multiply impute it using information from both data sources, borrowing the strength from each. We characterize the complete-data model as a product of an ‘outcome’ model for the probability of hospice-use and a ‘reporting’ model for the probability of underreporting from both sources, adjusting for other covariates. Assuming the reports of hospice-use from both sources are missing at random and the underreporting are conditionally independent, we develop a Bayesian multiple imputation algorithm and conduct multiple imputation analyses of patient hospice-use in demographic and clinical subgroups. The proposed approach yields more sensible results than alternative methods in our example. Our model is also related to dual system estimation in population censuses and dual exposure assessment in epidemiology. PMID:24804628

  9. Gastroesophageal reflux disease and patterns of reflux in patients with idiopathic pulmonary fibrosis using hypopharyngeal multichannel intraluminal impedance.

    PubMed

    Hoppo, T; Komatsu, Y; Jobe, B A

    2014-08-01

    Idiopathic pulmonary fibrosis (IPF) is a diffuse fibrotic lung disease of unknown etiology. The association between IPF and gastroesophageal reflux disease (GERD) has been suggested. The objective of this study was to determine the prevalence of GERD and assess the proximity of reflux events in patients with histologically proven IPF using hypopharyngeal multichannel intraluminal impedance (HMII). This is a retrospective review of prospectively collected data from patients with histologically confirmed IPF (via lung biopsy) who underwent objective esophageal physiology testing including high-resolution manometry and HMII. Defective lower esophageal sphincter (LES) was defined as either LES pressure of <5.0 mmHg, total length of LES of <2.4 cm, or intra-abdominal length of LES of <0.9 cm. Abnormal esophageal motility was considered present when failed swallows ≥30% and/or mean wave amplitude <30 mmHg was present. HMII used a specialized impedance catheter to directly measure laryngopharyngeal reflux (LPR) and full column reflux (reflux 2 cm distal to the upper esophageal sphincter). Based on the previous study of healthy subjects, abnormal proximal exposure was considered present when LPR ≥1/day and/or full column reflux ≥5/day were present. From October 2009 to June 2011, 46 patients were identified as having pulmonary fibrosis and sufficient HMII data. Of 46, 10 patients were excluded because of concomitant connective tissue diseases, and 8 patients were excluded because they had undergone lung transplantation, which may impact the patterns of reflux. The remaining 28 patients with histologically confirmed IPF (male 16, female 12) were included in this study. Mean age and BMI were 60.4 years (range, 41-78) and 28.4 (range, 21.1-38.1), respectively. All patients except one were symptomatic; 23 (82%) patients had concomitant typical GERD symptoms such as heartburn, whereas 4 (14%) patients had isolated pulmonary symptoms such as cough. Esophageal

  10. Combining PM2.5 Component Data from Multiple Sources: Data Consistency and Characteristics Relevant to Epidemiological Analyses of Predicted Long-Term Exposures

    PubMed Central

    Sheppard, Lianne; Larson, Timothy V.; Kaufman, Joel D.; Vedal, Sverre

    2015-01-01

    Background Regulatory monitoring data have been the exposure data resource most commonly applied to studies of the association between long-term PM2.5 components and health. However, data collected for regulatory purposes may not be compatible with epidemiological studies. Objectives We studied three important features of the PM2.5 component monitoring data to determine whether it would be appropriate to combine all available data from multiple sources for developing spatiotemporal prediction models in the National Particle Component and Toxicity (NPACT) study. Methods The NPACT monitoring data were collected in an extensive monitoring campaign targeting cohort participant residences. The regulatory monitoring data were obtained from the Chemical Speciation Network (CSN) and the Interagency Monitoring of Protected Visual Environments (IMPROVE). We performed exploratory analyses to examine features that could affect our approach to combining data: comprehensiveness of spatial coverage, comparability of analysis methods, and consistency in sampling protocols. In addition, we considered the viability of developing spatiotemporal prediction models given a) all available data, b) NPACT data only, and c) NPACT data with temporal trends estimated from other pollutants. Results The number of CSN/IMPROVE monitors was limited in all study areas. The different laboratory analysis methods and sampling protocols resulted in incompatible measurements between networks. Given these features we determined that it was preferable to develop our spatiotemporal models using only the NPACT data and under simplifying assumptions. Conclusions Investigators conducting epidemiological studies of long-term PM2.5 components need to be mindful of the features of the monitoring data and incorporate this understanding into the design of their monitoring campaigns and the development of their exposure prediction models. Citation Kim SY, Sheppard L, Larson TV, Kaufman JD, Vedal S. 2015. Combining

  11. Combining multiple measurement and isotope techniques to help target erosion hot-spots in the Great Barrier Reef catchments

    NASA Astrophysics Data System (ADS)

    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

  12. Targeting of multiple oncogenic signaling pathways by Hsp90 inhibitor alone or in combination with berberine for treatment of colorectal cancer.

    PubMed

    Su, Yen-Hao; Tang, Wan-Chun; Cheng, Ya-Wen; Sia, Peik; Huang, Chi-Chen; Lee, Yi-Chao; Jiang, Hsin-Yi; Wu, Ming-Heng; Lai, I-Lu; Lee, Jun-Wei; Lee, Kuen-Haur

    2015-10-01

    There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II-IV. Therefore, new, more-efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly downregulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVP-AUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1-β-catenin-cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC. PMID:25982393

  13. Effects of luminal nutrient absorption, intraluminal physical stimulation, and intravenous parenteral alimentation on the recovery responses of duodenal villus morphology following feed withdrawal in chickens.

    PubMed

    Tarachai, P; Yamauchi, K

    2000-11-01

    The aim of this study was to clarify which of the following three factors induces villus morphological recovery best: enteral nutrient absorption, intraluminal physical stimulation, or intravenous parenteral alimentation. At 142 d, male White Leghorn chickens (Gallus gallus domesticus) were divided into eight groups of five birds each as follows: 1) access given ad libitum to a commercial layer mash diet (CP, 17.5%; ME, 2,830 kcal/kg) (control), 2) 5-d feed withdrawal (feed withdrawal), 3) 3-d feed withdrawal (3-FW), followed by refeeding the same diet as the control for 2 d (refeeding), 4) 3-FW followed by force-feeding enteral hyperalimentation (enteral), 5) 3-FW followed by force-feeding an indigestible (nonabsorbable) substance (kaolin), 6) 3-FW followed by force-feeding water for 2 d (force-fed control), 7) 3-FW followed by parenteral hyperalimentation (parenteral), and 8) 3-FW followed by no alimentation (sham control) for 2 d. In the refeeding and enteral groups, BW significantly recovered (P < 0.05), and in the parenteral group, BW tended to increase, suggesting that nutrients were enterally and parenterally absorbed, respectively. The BW in the remaining three groups showed a significant decrease (P < 0.05), indicating that kaolin could not be absorbed enterally. Compared with the feed withdrawal group, villus height, cell mitosis, and villus tip surface morphology of refeeding and enteral groups exhibited rapid villus morphological recovery. Villus morphological recovery of the enteral group appears to have been caused by enteral nutrient absorption. However, villus morphology in the kaolin treatment was not different from that in the feed withdrawal group, which suggests that intraluminal physical stimulation had no effect on villus morphological recovery. On the other hand, the parenteral group showed no effect on villus morphological recovery, which suggests that the parenteral nutrient supplied to the villi via the blood could not induce villus

  14. MR guided thermal therapy of pancreatic tumors with endoluminal, intraluminal and interstitial catheter-based ultrasound devices: preliminary theoretical and experimental investigations

    NASA Astrophysics Data System (ADS)

    Prakash, Punit; Salgaonkar, Vasant A.; Scott, Serena J.; Jones, Peter; Hensley, Daniel; Holbrook, Andrew; Plata, Juan; Sommer, Graham; Diederich, Chris J.

    2013-02-01

    Image-guided thermal interventions have been proposed for potential palliative and curative treatments of pancreatic tumors. Catheter-based ultrasound devices offer the potential for temporal and 3D spatial control of the energy deposition profile. The objective of this study was to apply theoretical and experimental techniques to investigate the feasibility of endogastric, intraluminal and transgastric catheter-based ultrasound for MR guided thermal therapy of pancreatic tumors. The transgastric approach involves insertion of a catheter-based ultrasound applicator (array of 1.5 mm OD x 10 mm transducers, 360° or sectored 180°, ~7 MHz frequency, 13-14G cooling catheter) directly into the pancreas, either endoscopically or via image-guided percutaneous placement. An intraluminal applicator, of a more flexible but similar construct, was considered for endoscopic insertion directly into the pancreatic or biliary duct. An endoluminal approach was devised based on an ultrasound transducer assembly (tubular, planar, curvilinear) enclosed in a cooling balloon which is endoscopically positioned within the stomach or duodenum, adjacent to pancreatic targets from within the GI tract. A 3D acoustic bio-thermal model was implemented to calculate acoustic energy distributions and used a FEM solver to determine the transient temperature and thermal dose profiles in tissue during heating. These models were used to determine transducer parameters and delivery strategies and to study the feasibility of ablating 1-3 cm diameter tumors located 2-10 mm deep in the pancreas, while thermally sparing the stomach wall. Heterogeneous acoustic and thermal properties were incorporated, including approximations for tumor desmoplasia and dynamic changes during heating. A series of anatomic models based on imaging scans of representative patients were used to investigate the three approaches. Proof of concept (POC) endogastric and transgastric applicators were fabricated and experimentally

  15. Multiple hemangiomas of the urinary bladder in a child with gross hematuria

    PubMed Central

    Kim, Yeun Yoon; Kim, Myung-Joon; Lee, Mi-Jung; Kim, Ji-Ye

    2015-01-01

    We report a case of multiple hemangiomas involving the urinary bladder in a 4-year-old boy who presented with recurrent episodes of gross hematuria. On ultrasonography, compared with the bladder wall, the lesions presented as multiple isoechoic polypoid intraluminal masses with mildly increased vascularity on color Doppler exam. Cavernous hemangioma was confirmed by cold-cup biopsy, and the all lesions were coagulated with a Holmium laser. Despite their rarity, bladder hemangiomas should be included in the differential diagnosis of multiple intravesical masses in children with gross hematuria. PMID:25672772

  16. 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

    NASA Astrophysics Data System (ADS)

    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).

  17. Combined single crystal polarized XAFS and XRD at high pressure: probing the interplay between lattice distortions and electronic order at multiple length scales in high T c cuprates

    DOE PAGES

    Fabbris, G.; Hücker, M.; Gu, G. D.; Tranquada, J. M.; Haskel, D.

    2016-07-14

    Some of the most exotic material properties derive from electronic states with short correlation length (~10-500 Å), suggesting that the local structural symmetry may play a relevant role in their behavior. In this study, we discuss the combined use of polarized x-ray absorption fine structure and x-ray diffraction at high pressure as a powerful method to tune and probe structural and electronic orders at multiple length scales. Besides addressing some of the technical challenges associated with such experiments, we illustrate this approach with results obtained in the cuprate La1.875Ba0.125CuO4, in which the response of electronic order to pressure can onlymore » be understood by probing the structure at the relevant length scales.« less

  18. Fate of biopolymers during rapeseed meal and wheat bran composting as studied by two-dimensional correlation spectroscopy in combination with multiple fluorescence labeling techniques.

    PubMed

    Wang, Li-Ping; Shen, Qi-Rong; Yu, Guang-Hui; Ran, Wei; Xu, Yang-Chun

    2012-02-01

    Detailed knowledge of the molecular events during composting is important in improving the efficiency of this process. By combining two-dimensional Fourier transform infrared (FTIR) correlation spectroscopy and multiple fluorescent labeling, it was possible to study the degradation of biopolymers during rapeseed meal and wheat bran composting. Two-dimensional FTIR correlation spectroscopy provided structural information and was used to deconvolute overlapping bands found in the compost FTIR spectra. The degradation of biopolymers in rapeseed meal and wheat bran composts followed the sequence: cellulose, heteropolysaccharides, and proteins. Fluorescent labeling suggested that cellulose formed an intact network-like structure and the other biopolymers were embedded in the core of this structure. The sequence of degradation of biopolymers during composting was related to their distribution patterns.

  19. Very simple combination of TROSY, CRINEPT and multiple quantum coherence for signal enhancement in an HN(CO)CA experiment for large proteins.

    PubMed

    Bayrhuber, Monika; Riek, Roland

    2011-04-01

    Sensitivity enhancement in liquid state nuclear magnetic resonance (NMR) triple resonance experiments for the sequential assignment of proteins is important for the investigation of large proteins or protein complexes. We present here the 3D TROSY-MQ/CRINEPT-HN(CO)CA which makes use of a ¹⁵N-¹H-TROSY element and a ¹³C'-¹³CA CRINEPT step combined with a multiple quantum coherence during the ¹³CA evolution period. Because of the introduction of these relaxation-optimized elements and 10 less pulses required, when compared with the conventional TROSY-HN(CO)CA experiment an average signal enhancement of a factor of 1.8 was observed for the membrane protein-detergent complex KcsA with a rotational correlation time τ(c) of around 60 ns.

  20. Combining multiple remote sensors with reanalysis and a radiative transfer model to assess the microphysical impact of smoke on cirrus clouds

    NASA Astrophysics Data System (ADS)

    Kablick, G. P.

    2011-12-01

    A multi-spectral technique for retrieving properties of smoke contaminated ice clouds is evaluated. This method utilizes Earth orbiting active and passive remote sensors combined with atmospheric reanalysis and a multiple scattering, single column radiative transfer algorithm. This study focuses on a specific type of cirrus cloud that exhibits IR radiances, lidar backscatter values, color ratios and depolarization ratios comparable to thick cirrus as observed by MODIS and CALIPSO. However, the radar reflectivities as determined by CloudSat are significantly lower than expected for clouds with such large visible optical depths. This work also demonstrates the sensitivity of retrievals to a priori assumptions by using a few notable cases. Collocated data observed during the boreal fire season of 2010 is analyzed using this methodology as a first step to ascertain the impact that pyroconvection may have on ice cloud properties.

  1. Very simple combination of TROSY, CRINEPT and multiple quantum coherence for signal enhancement in an HN(CO)CA experiment for large proteins

    NASA Astrophysics Data System (ADS)

    Bayrhuber, Monika; Riek, Roland

    2011-04-01

    Sensitivity enhancement in liquid state nuclear magnetic resonance (NMR) triple resonance experiments for the sequential assignment of proteins is important for the investigation of large proteins or protein complexes. We present here the 3D TROSY-MQ/CRINEPT-HN(CO)CA which makes use of a 15N- 1H-TROSY element and a 13C'- 13CA CRINEPT step combined with a multiple quantum coherence during the 13CA evolution period. Because of the introduction of these relaxation-optimized elements and 10 less pulses required, when compared with the conventional TROSY-HN(CO)CA experiment an average signal enhancement of a factor of 1.8 was observed for the membrane protein-detergent complex KcsA with a rotational correlation time τ c of around 60 ns.

  2. Fate of biopolymers during rapeseed meal and wheat bran composting as studied by two-dimensional correlation spectroscopy in combination with multiple fluorescence labeling techniques.

    PubMed

    Wang, Li-Ping; Shen, Qi-Rong; Yu, Guang-Hui; Ran, Wei; Xu, Yang-Chun

    2012-02-01

    Detailed knowledge of the molecular events during composting is important in improving the efficiency of this process. By combining two-dimensional Fourier transform infrared (FTIR) correlation spectroscopy and multiple fluorescent labeling, it was possible to study the degradation of biopolymers during rapeseed meal and wheat bran composting. Two-dimensional FTIR correlation spectroscopy provided structural information and was used to deconvolute overlapping bands found in the compost FTIR spectra. The degradation of biopolymers in rapeseed meal and wheat bran composts followed the sequence: cellulose, heteropolysaccharides, and proteins. Fluorescent labeling suggested that cellulose formed an intact network-like structure and the other biopolymers were embedded in the core of this structure. The sequence of degradation of biopolymers during composting was related to their distribution patterns. PMID:22182472

  3. The influence of combined genotypes of the HLADRB1*1501 and CD24 single nucleotide polymorphism on disease severity of Iranian multiple sclerosis patients.

    PubMed

    Ghlichnia, Hossein Ali; Kollaee, Abolghasem; Gaffarpoor, Majid; Movafagh, Abolfazl; Ghlichnia, Babak; Zamani, Mahdi

    2014-01-01

    Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. It is a clinically heterogeneous disorder especially in terms of disease severity. Current investigations suggest that genes and gene-gene interactions not only influence on susceptibility to MS but also affect the disease severity. In this study, we investigated the contribution of the HLADRB1*1501 allele and single nucleotide polymorphism (SNP) in CD24 gene and also combined genotypes of the HLADRB1*1501 and CD24 SNP to disease severity in Iranian MS patients. We have reported previously that the HLA- DRB1*1501 allele and the CD24v/v genotype associated with disease susceptibility and some other studies proposed that HLA-DRB1*1501 allele be associated with MS severity. In this study, the results showed a significant difference in the Multiple Sclerosis Severity Score (MSSS) of the nine different genotypes (F=2.838, P=0.007). Subsequent analysis revealed a statistically significant difference in the MSSS between the MS patients who were carriers of HLA-DRB1*1501/1501 and those who were not carriers of HLA-DRB1*1501/1501 genotypes (P=0.04). Moreover, the MS patients carrying combined genotypes of the HLA- DRB1*1501/x-CD24 v/v had statistically severe disease than the patients who did not carry the HLA- DRB1*1501- CD24 v/v (P=0.047). In conclusion, our findings suggest that, HLA-DRB1*1501/1501 and bigenic genotypes of the HLA- DRB1*1501/x- CD24 v/v may influence on disease severity in Iranian MS patients.

  4. 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

    PubMed Central

    Kaumaya, Pravin TP

    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. PMID:25874884

  5. 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.

    PubMed

    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.

  6. The effect of spironolactone on the elemental composition of the intraluminal fluids of the seminiferous tubules, rete testis and epididymis of the rat.

    PubMed

    Jenkins, A D; Lechene, C P; Howards, S S

    1983-04-01

    Embryologically, the epididymis and renal collecting tubules develop from the mesonephric duct. Aldosterone enhances the reabsorption of sodium from the collecting tubule, and there is evidence that sodium is removed from the epididymal lumen against a concentration gradient. Rats were treated with spironolactone, an aldosterone antagonist, and the concentrations of seven elements, including sodium, were measured in intraluminal fluids from the testis and epididymis. The sodium concentration in caput epididymidal fluid rose (102.5 +/- 4.4 to 128.0 +/- 6.8 mmol./l., p less than 0.01) after 14 days of spironolactone treatment. This finding is consistent with the hypothesis that aldosterone acts on the caput epididymidis, like the collecting tubule, to augment the removal of sodium from luminal fluid. PMID:6842723

  7. A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice

    PubMed Central

    Morris, Gary P.; Gladbach, Amadeus; Ittner, Lars M.; Vissel, Bryce

    2016-01-01

    The intraluminal filament model of middle cerebral artery occlusion (MCAO) in mice and rats has been plagued by inconsistency, owing in part to the multitude of variables requiring control. In this study we investigated the impact of several major variables on survival rate, lesion volume, neurological scores, cerebral blood flow (CBF) and body weight including filament width, time after reperfusion, occlusion time and the choice of surgical method. Using the Koizumi method, we found ischemic injury can be detected as early as 30 min after reperfusion, to a degree that is not statistically different from 24 h post-perfusion, using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We also found a distinct increase in total lesion volume with increasing occlusion time, with 30–45 min a critical time for the development of large, reproducible lesions. Furthermore, although we found no significant difference in total lesion volume generated by the Koizumi and Longa methods of MCAO, nor were survival rates appreciably different between the two at 4 h after reperfusion, the Longa method produces significantly greater reperfusion. Finally, we found no statistical evidence to support the exclusion of data from animals experiencing a CBF reduction of <70% in the MCA territory following MCAO, using laser-Doppler flowmetry. Instead we suggest the main usefulness of laser-Doppler flowmetry is for guiding filament placement and the identification of subarachnoid haemorrhages and premature reperfusion. In summary, this study provides detailed evaluation of the Koizumi method of intraluminal filament MCAO in mice and a direct comparison to the Longa method. PMID:26870954

  8. A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice.

    PubMed

    Morris, Gary P; Wright, Amanda L; Tan, Richard P; Gladbach, Amadeus; Ittner, Lars M; Vissel, Bryce

    2016-01-01

    The intraluminal filament model of middle cerebral artery occlusion (MCAO) in mice and rats has been plagued by inconsistency, owing in part to the multitude of variables requiring control. In this study we investigated the impact of several major variables on survival rate, lesion volume, neurological scores, cerebral blood flow (CBF) and body weight including filament width, time after reperfusion, occlusion time and the choice of surgical method. Using the Koizumi method, we found ischemic injury can be detected as early as 30 min after reperfusion, to a degree that is not statistically different from 24 h post-perfusion, using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We also found a distinct increase in total lesion volume with increasing occlusion time, with 30-45 min a critical time for the development of large, reproducible lesions. Furthermore, although we found no significant difference in total lesion volume generated by the Koizumi and Longa methods of MCAO, nor were survival rates appreciably different between the two at 4 h after reperfusion, the Longa method produces significantly greater reperfusion. Finally, we found no statistical evidence to support the exclusion of data from animals experiencing a CBF reduction of <70% in the MCA territory following MCAO, using laser-Doppler flowmetry. Instead we suggest the main usefulness of laser-Doppler flowmetry is for guiding filament placement and the identification of subarachnoid haemorrhages and premature reperfusion. In summary, this study provides detailed evaluation of the Koizumi method of intraluminal filament MCAO in mice and a direct comparison to the Longa method. PMID:26870954

  9. Combining multiple feature representations and AdaBoost ensemble learning for reducing false-positive detections in computer-aided detection of masses on mammograms.

    PubMed

    Choi, Jae Young; Kim, Dae Hoe; Plataniotis, Konstantinos N; Ro, Yong Man

    2012-01-01

    One of the drawbacks of current Computer-aided Detection (CADe) systems is a high number of false-positive (FP) detections, especially for detecting mass abnormalities. In a typical CADe system, classifier design is one of the key steps for determining FP detection rates. This paper presents the effective classifier ensemble system for tackling FP reduction problem in CADe. To construct ensemble consisting of correct classifiers while disagreeing with each other as much as possible, we develop a new ensemble construction solution that combines data resampling underpinning AdaBoost learning with the use of different feature representations. In addition, to cope with the limitation of weak classifiers in conventional AdaBoost, our method has an effective mechanism for tuning the level of weakness of base classifiers. Further, for combining multiple decision outputs of ensemble members, a weighted sum fusion strategy is used to maximize a complementary effect for correct classification. Comparative experiments have been conducted on benchmark mammogram dataset. Results show that the proposed classifier ensemble outperforms the best single classifier in terms of reducing the FP detections of masses.

  10. Complete suppression of the fluorophore fluorescence by combined effect of multiple fluorescence quenching groups: A fluorescent sensor for Cu²⁺ with zero background signals.

    PubMed

    Long, Lingliang; Wu, Yanjun; Wang, Lin; Gong, Aihua; Hu, Rongfeng; Zhang, Chi

    2016-02-18

    The reaction-based fluorescent sensors have attracted increasing attention in the past decades. However, the application of these sensors for accurate sensing was significantly retarded by the background fluorescence from the sensors themselves. In this work, we demonstrated a novel strategy that the background fluorescence of the sensor could be completely eliminated by the combined effect of multiple fluorescence quenching groups. Based on this new strategy, as proof-of-principle study, a fluorescent sensor (CuFS) for Cu(2+) was judiciously developed. In CuFS, three types of fluorescence quenching groups were directly tethered to a commonly used coumarin fluorophore. The fluorescence of coumarin fluorophore in CuFS was completely suppressed by the combined effect of these fluorescence quenching groups. Upon treatment with 22 μM Cu(2+), sensor CuFS achieved a dramatic fluorescence enhancement (fluorescence intensity enhanced up to 811-fold) centered at 469 nm. The detection limits was determined to be 12.3 nM. The fluorescence intensity enhancement also showed a good linearity with the Cu(2+) concentration in the range of 12.3 nM to 2 μM. By fabricating test strips, sensor CuFS can be utilized as a simple tool to detect Cu(2+) in water samples. Furthermore, the fluorescent sensor was successfully applied in detecting different concentration of Cu(2+) in living cells.

  11. Complete suppression of the fluorophore fluorescence by combined effect of multiple fluorescence quenching groups: A fluorescent sensor for Cu²⁺ with zero background signals.

    PubMed

    Long, Lingliang; Wu, Yanjun; Wang, Lin; Gong, Aihua; Hu, Rongfeng; Zhang, Chi

    2016-02-18

    The reaction-based fluorescent sensors have attracted increasing attention in the past decades. However, the application of these sensors for accurate sensing was significantly retarded by the background fluorescence from the sensors themselves. In this work, we demonstrated a novel strategy that the background fluorescence of the sensor could be completely eliminated by the combined effect of multiple fluorescence quenching groups. Based on this new strategy, as proof-of-principle study, a fluorescent sensor (CuFS) for Cu(2+) was judiciously developed. In CuFS, three types of fluorescence quenching groups were directly tethered to a commonly used coumarin fluorophore. The fluorescence of coumarin fluorophore in CuFS was completely suppressed by the combined effect of these fluorescence quenching groups. Upon treatment with 22 μM Cu(2+), sensor CuFS achieved a dramatic fluorescence enhancement (fluorescence intensity enhanced up to 811-fold) centered at 469 nm. The detection limits was determined to be 12.3 nM. The fluorescence intensity enhancement also showed a good linearity with the Cu(2+) concentration in the range of 12.3 nM to 2 μM. By fabricating test strips, sensor CuFS can be utilized as a simple tool to detect Cu(2+) in water samples. Furthermore, the fluorescent sensor was successfully applied in detecting different concentration of Cu(2+) in living cells. PMID:26826684

  12. Combination treatment of fingolimod with antidepressants in relapsing–remitting multiple sclerosis patients with depression: a multicentre, open-label study – REGAIN

    PubMed Central

    Bayas, Antonios; Schuh, Katrin; Baier, Monika; Vormfelde, Stefan Viktor; Koppai-Reiner, Joachim

    2016-01-01

    Objectives: Approximately one in two patients with multiple sclerosis (MS) suffer from comorbid depression. The primary objective of this study was to evaluate the safety and tolerability of fingolimod and antidepressant combination in relapsing–remitting MS patients with mild-to-moderate depression. Efficacy outcome variables were quality of life (QoL), fatigue, disability and depression. Methods: Patients received open-label fingolimod 0.5 mg over 2 weeks, followed by fingolimod plus citalopram (40 mg), fluoxetine (40 mg) or venlafaxine (150 mg) over 16 weeks. The antidepressant was selected at the physician’s discretion. Results: In total, 54 patients were recruited at 25 centres across Germany. No new safety signals (including cardiac) emerged compared with previous clinical studies. Adverse events (mostly mild-to-moderate) were reported in 43 patients. A total of three patients had serious adverse events and 10 discontinued the study. QoL (mean [95% confidence interval]) improved by 2.2 (−3.3, −1.2; Patient Reported Indices for MS questionnaire), fatigue by 8.2 (−13.1, −3.3; modified Fatigue Impact Scale) and depression by 6.3 (−8.4, −4.2; Hamilton Depression Scale) points. However, the results must be interpreted cautiously owing to limited patient numbers. Conclusions: Combination of fingolimod with antidepressant medication showed no unexpected safety signals. Patient-reported outcomes (QoL, disability, fatigue and depression) remained stable or improved. PMID:27582893

  13. Nodal combined blue nevus and benign nevus cells in multiple axillary sentinel nodes in a patient with breast carcinoma: report of a case.

    PubMed

    Begum, S M K Nahar; Lomme, Michele; Quddus, M Ruhul

    2014-09-01

    Combined blue nevus and benign nevus cells were identified in the same sentinel lymph node. Blue nevus alone was also present in an additional sentinel lymph node in the same axilla in a patient who underwent needle localization, wide local excision, and sentinel lymph node biopsy for her pT1cN1mi(sn)M(na) invasive duct carcinoma of the breast. Of the 4 sentinel lymph nodes, 1 showed micrometastasis and 2 other lymph nodes showed blue nevus involving the capsule and trabeculae of the nodes. The patient had no significant previous clinical history of any skin tumors and had a negative clinical examination for malignant melanoma or pigmented skin lesions after the diagnosis of nodal blue nevus. To our knowledge, this is the first case report of combined blue nevi involving multiple sentinel lymph nodes in the same axilla. An equally interesting finding is the presence of benign nonpigmented nevus cells in continuation with the blue nevus in the same node.

  14. A methodology for combining multiple commercial data sources to improve measurement of the food and alcohol environment: applications of geographical information systems.

    PubMed

    Mendez, Dara D; Duell, Jessica; Reiser, Sarah; Martin, Deborah; Gradeck, Robert; Fabio, Anthony

    2014-11-01

    Commercial data sources have been increasingly used to measure and locate community resources. We describe a methodology for combining and comparing the differences in commercial data of the food and alcohol environment. We used commercial data from two commercial databases (InfoUSA and Dun&Bradstreet) for 2003 and 2009 to obtain information on food and alcohol establishments and developed a matching process using computer algorithms and manual review by applying ArcGIS to geocode addresses, standard industrial classification and North American industry classification taxonomy for type of establishment and establishment name. We constructed population and area-based density measures (e.g. grocery stores) and assessed differences across data sources and used ArcGIS to map the densities. The matching process resulted in 8,705 and 7,078 unique establishments for 2003 and 2009, respectively. There were more establishments captured in the combined dataset than relying on one data source alone, and the additional establishments captured ranged from 1,255 to 2,752 in 2009. The correlations for the density measures between the two data sources was highest for alcohol outlets (r = 0.75 and 0.79 for per capita and area, respectively) and lowest for grocery stores/supermarkets (r = 0.32 for both). This process for applying geographical information systems to combine multiple commercial data sources and develop measures of the food and alcohol environment captured more establishments than relying on one data source alone. This replicable methodology was found to be useful for understanding the food and alcohol environment when local or public data are limited.

  15. Rapid Identification and Multiple Susceptibility Testing of Pathogens from Positive-Culture Sterile Body Fluids by a Combined MALDI-TOF Mass Spectrometry and Vitek Susceptibility System

    PubMed Central

    Tian, Yueru; Zheng, Bing; Wang, Bei; Lin, Yong; Li, Min

    2016-01-01

    Infections of the bloodstream, central nervous system, peritoneum, joints, and other sterile areas are associated with high morbidity and sequelae risk. Timely initiation of effective antimicrobial therapy is crucial to improving patient prognosis. However, standard final identification and antimicrobial susceptibility tests (ASTs) are reported 16–48 h after a positive alert. For a rapid, effective and low-cost diagnosis, we combined matrix-assisted laser desorption/ionization time of flight mass spectrometry with a Vitek AST system, and performed rapid microbial identification (RMI) and rapid multiple AST (RMAST) on non-duplicated positive body fluid cultures collected from a hospital in Shanghai, China. Sterile body fluid positive culture and blood positive culture caused by Gram negative (GN) or polymicrobial were applied to the MALDI–TOF measurement directly. When positive blood culture caused by Gram positive (GP) bacteria or yeasts, they were resuspended in 1 ml brain heart infusion for 2 or 4 h enrichment, respectively. Regardless of enrichment, the RMI (completed in 40 min per sample) accurately identified GN and GP bacteria (98.9 and 87.2%, respectively), fungi (75.7%), and anaerobes (94.7%). Dominant species in multiple cultures and bacteria that failed to grow on the routing plates were correctly identified in 81.2 and 100% of cases, respectively. The category agreements of RMAST results, determined in the presence of various antibiotics, were similarly to previous studies. The RMI and RMAST results not only reduce the turnaround time of the patient report by 18–36 h, but also indicate whether a patient's antibiotic treatment should be accelerated, ceased or de-escalated, and adjusted the essential drugs modification for an optimized therapy. PMID:27148212

  16. Cellular and Molecular Mechanisms Underlie the Anti-Tumor Activities Exerted by Walterinnesia aegyptia Venom Combined with Silica Nanoparticles against Multiple Myeloma Cancer Cell Types

    PubMed Central

    Badr, Gamal; Al-Sadoon, Mohamed K.; Abdel-Maksoud, Mostafa A.; Rabah, Danny M.; El-Toni, Ahmed M.

    2012-01-01

    Multiple myeloma (MM) is a clonal disease of plasma cells that remains incurable despite the advent of several novel therapeutics. In this study, we aimed to delineate the impact of snake venom extracted from Walterinnesia aegyptia (WEV) alone or in combination with silica nanoparticles (WEV+NP) on primary MM cells isolated from patients diagnosed with MM as well as on two MM cell lines, U266 and RPMI 8226. The IC50 values of WEV and WEV+NP that significantly decreased MM cell viability without affecting the viability of normal peripheral mononuclear cells (PBMCs) were determined to be 25 ng/ml and 10 ng/ml, respectively. Although both WEV (25 ng/ml) and WEV+NP (10 ng/ml) decreased the CD54 surface expression without affecting the expression of CXCR4 (CXCL12 receptor) on MM cells, they significantly reduced the ability of CXC chemokine ligand 12 (CXCL12) to induce actin cytoskeleton rearrangement and the subsequent reduction in chemotaxis. It has been established that the binding of CXCL12 to its receptor CXCR4 activates multiple intracellular signal transduction pathways that regulate MM cell chemotaxis, adhesion, and proliferation. We found that WEV and WEV+NP clearly decreased the CXCL12/CXCR4-mediated activation of AKT, ERK, NFκB and Rho-A using western blot analysis; abrogated the CXCL12-mediated proliferation of MM cells using the CFSE assay; and induced apoptosis in MM cell as determined by PI/annexin V double staining followed by flow cytometry analysis. Monitoring the expression of B-cell CCL/Lymphoma 2 (Bcl-2) family members and their role in apoptosis induction after treatment with WEV or WEV+NP revealed that the combination of WEV with NP robustly decreased the expression of the anti-apoptotic effectors Bcl-2, BclXL and Mcl-1; conversely increased the expression of the pro-apoptotic effectors Bak, Bax and Bim; and altered the mitochondrial membrane potential in MM cells. Taken together, our data reveal the biological effects of WEV and WEV+NP and the

  17. Cellular and molecular mechanisms underlie the anti-tumor activities exerted by Walterinnesia aegyptia venom combined with silica nanoparticles against multiple myeloma cancer cell types.

    PubMed

    Badr, Gamal; Al-Sadoon, Mohamed K; Abdel-Maksoud, Mostafa A; Rabah, Danny M; El-Toni, Ahmed M

    2012-01-01

    Multiple myeloma (MM) is a clonal disease of plasma cells that remains incurable despite the advent of several novel therapeutics. In this study, we aimed to delineate the impact of snake venom extracted from Walterinnesia aegyptia (WEV) alone or in combination with silica nanoparticles (WEV+NP) on primary MM cells isolated from patients diagnosed with MM as well as on two MM cell lines, U266 and RPMI 8226. The IC(50) values of WEV and WEV+NP that significantly decreased MM cell viability without affecting the viability of normal peripheral mononuclear cells (PBMCs) were determined to be 25 ng/ml and 10 ng/ml, respectively. Although both WEV (25 ng/ml) and WEV+NP (10 ng/ml) decreased the CD54 surface expression without affecting the expression of CXCR4 (CXCL12 receptor) on MM cells, they significantly reduced the ability of CXC chemokine ligand 12 (CXCL12) to induce actin cytoskeleton rearrangement and the subsequent reduction in chemotaxis. It has been established that the binding of CXCL12 to its receptor CXCR4 activates multiple intracellular signal transduction pathways that regulate MM cell chemotaxis, adhesion, and proliferation. We found that WEV and WEV+NP clearly decreased the CXCL12/CXCR4-mediated activation of AKT, ERK, NFκB and Rho-A using western blot analysis; abrogated the CXCL12-mediated proliferation of MM cells using the CFSE assay; and induced apoptosis in MM cell as determined by PI/annexin V double staining followed by flow cytometry analysis. Monitoring the expression of B-cell CCL/Lymphoma 2 (Bcl-2) family members and their role in apoptosis induction after treatment with WEV or WEV+NP revealed that the combination of WEV with NP robustly decreased the expression of the anti-apoptotic effectors Bcl-2, Bcl(XL) and Mcl-1; conversely increased the expression of the pro-apoptotic effectors Bak, Bax and Bim; and altered the mitochondrial membrane potential in MM cells. Taken together, our data reveal the biological effects of WEV and WEV+NP and

  18. Internal correction of spectral interferences and mass bias for selenium metabolism studies using enriched stable isotopes in combination with multiple linear regression.

    PubMed

    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

  19. Combined effects of smoking, anti-EBNA antibodies, and HLA-DRB1*1501 on multiple sclerosis risk(e–Pub ahead of print)

    PubMed Central

    Simon, K.C.; van der Mei, I.A.F.; Munger, K.L.; Ponsonby, A.; Dickinson, J.; Dwyer, T.; Sundström, P.; Ascherio, A.

    2010-01-01

    Objective: To examine the interplay between smoking, serum antibody titers to the Epstein-Barr virus nuclear antigens (anti-EBNA), and HLA-DR15 on multiple sclerosis (MS) risk. Methods: Individual and pooled analyses were conducted among 442 cases and 865 controls from 3 MS case-control studies—a nested case-control study in the Nurses' Health Study/Nurses' Health Study II, the Tasmanian MS Study, and a Swedish MS Study. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for the association between smoking, anti-EBNA titers, HLA-DR15, and MS risk. Study estimates were pooled using inverse variance weights to determine a combined effect and p value. Results: Among MS cases, anti-EBNA titers were significantly higher in ever smokers compared to never smokers. The increased risk of MS associated with high anti-EBNA Ab titers was stronger among ever smokers (OR = 3.9, 95% CI = 2.7–5.7) compared to never smokers (OR = 1.8, 95% CI = 1.4–2.3; p for interaction = 0.001). The increased risk of MS associated with a history of smoking was no longer evident after adjustment for anti-EBNA Ab titers. No modification or confounding by HLA-DR15 was observed. The increased risk of MS associated with ever smoking was only observed among those who had high anti-EBNA titers (OR = 1.7, 95% CI = 1.1–2.6). Conclusions: Smoking appears to enhance the association between high anti-EBNA titer and increased multiple sclerosis (MS) risk. The association between HLA-DR15 and MS risk is independent of smoking. Further work is necessary to elucidate possible biologic mechanisms to explain this finding. GLOSSARY anti-EBNA = antibody titers to the Epstein-Barr virus nuclear antigens; EBV = Epstein-Barr virus; MS = multiple sclerosis; NHS = Nurses' Health Study; NHSII = Nurses' Health Study II; NSHDS = Northern Sweden Health and Disease Study Cohort; OR = odds ratio. PMID:20375311

  20. Mapping three-dimensional surface deformation by combining multiple-aperture interferometry and conventional interferometry: Application to the June 2007 eruption of Kilauea Volcano, Hawaii

    USGS Publications Warehouse

    Jung, H.-S.; Lu, Zhiming; Won, J.-S.; Poland, Michael P.; Miklius, Asta

    2011-01-01

    Surface deformation caused by an intrusion and small eruption during June 17-19, 2007, along the East Rift Zone of Kilauea Volcano, Hawaii, was three-dimensionally reconstructed from radar interferograms acquired by the Advanced Land Observing Satellite (ALOS) phased-array type L-band synthetic aperture radar (SAR) (PALSAR) instrument. To retrieve the 3-D surface deformation, a method that combines multiple-aperture interferometry (MAI) and conventional interferometric SAR (InSAR) techniques was applied to one ascending and one descending ALOS PALSAR interferometric pair. The maximum displacements as a result of the intrusion and eruption are about 0.8, 2, and 0.7 m in the east, north, and up components, respectively. The radar-measured 3-D surface deformation agrees with GPS data from 24 sites on the volcano, and the root-mean-square errors in the east, north, and up components of the displacement are 1.6, 3.6, and 2.1 cm, respectively. Since a horizontal deformation of more than 1 m was dominantly in the north-northwest-south-southeast direction, a significant improvement of the north-south component measurement was achieved by the inclusion of MAI measurements that can reach a standard deviation of 3.6 cm. A 3-D deformation reconstruction through the combination of conventional InSAR and MAI will allow for better modeling, and hence, a more comprehensive understanding, of the source geometry associated with volcanic, seismic, and other processes that are manifested by surface deformation.

  1. Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency.

    PubMed

    Olsen, Rikke K J; Koňaříková, Eliška; Giancaspero, Teresa A; Mosegaard, Signe; Boczonadi, Veronika; Mataković, Lavinija; Veauville-Merllié, Alice; Terrile, Caterina; Schwarzmayr, Thomas; Haack, Tobias B; Auranen, Mari; Leone, Piero; Galluccio, Michele; Imbard, Apolline; Gutierrez-Rios, Purificacion; Palmfeldt, Johan; Graf, Elisabeth; Vianey-Saban, Christine; Oppenheim, Marcus; Schiff, Manuel; Pichard, Samia; Rigal, Odile; Pyle, Angela; Chinnery, Patrick F; Konstantopoulou, Vassiliki; Möslinger, Dorothea; Feichtinger, René G; Talim, Beril; Topaloglu, Haluk; Coskun, Turgay; Gucer, Safak; Botta, Annalisa; Pegoraro, Elena; Malena, Adriana; Vergani, Lodovica; Mazzà, Daniela; Zollino, Marcella; Ghezzi, Daniele; Acquaviva, Cecile; Tyni, Tiina; Boneh, Avihu; Meitinger, Thomas; Strom, Tim M; Gregersen, Niels; Mayr, Johannes A; Horvath, Rita; Barile, Maria; Prokisch, Holger

    2016-06-01

    Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and a neuromuscular phenotype. Despite recent advances in understanding the genetic basis of MADD, a number of cases remain unexplained. Here, we report clinically relevant variants in FLAD1, which encodes FAD synthase (FADS), as the cause of MADD and respiratory-chain dysfunction in nine individuals recruited from metabolic centers in six countries. In most individuals, we identified biallelic frameshift variants in the molybdopterin binding (MPTb) domain, located upstream of the FADS domain. Inasmuch as FADS is essential for cellular supply of FAD cofactors, the finding of biallelic frameshift variants was unexpected. Using RNA sequencing analysis combined with protein mass spectrometry, we discovered FLAD1 isoforms, which only encode the FADS domain. The existence of these isoforms might explain why affected individuals with biallelic FLAD1 frameshift variants still harbor substantial FADS activity. Another group of individuals with a milder phenotype responsive to riboflavin were shown to have single amino acid changes in the FADS domain. When produced in E. coli, these mutant FADS proteins resulted in impaired but detectable FADS activity; for one of the variant proteins, the addition of FAD significantly improved protein stability, arguing for a chaperone-like action similar to what has been reported in other riboflavin-responsive inborn errors of metabolism. In conclusion, our studies identify FLAD1 variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD and shed light on the mechanisms by which FADS ensures cellular FAD homeostasis. PMID:27259049

  2. Combined expression of miR-34a and Smac mediated by oncolytic vaccinia virus synergistically promote anti-tumor effects in Multiple Myeloma.

    PubMed

    Lei, Wen; Wang, Shibing; Yang, Chunmei; Huang, Xianbo; Chen, Zhenzhen; He, Wei; Shen, Jianping; Liu, Xinyuan; Qian, Wenbin

    2016-01-01

    Despite great progress made in the treatment of multiple myeloma (MM), it is still incurable. Promising phase II clinical results have been reported recently for oncolytic vaccinia virus (OVV) clinic therapeutics. One reason for this has focused on the critical therapeutic importance of the immune response raised by these viruses. However, few studies have performed their applications as an optimal delivery system for therapeutic gene, especially miRNA in MM. In this study, we constructed two novel OVVs (TK deletion) that express anti-tumor genes, miR-34a and Smac, respectively, in MM cell lines and xenograft model. The results demonstrated that the novel OVV can effectively infect MM cell lines, and forcefully enhance the exogenous gene (miR-34a or Smac) expression. Furthermore, utilization of VV-miR-34a combined with VV-Smac synergistically inhibited tumor growth and induced apoptosis in vitro and in vivo. The underlying mechanism is proposed that blocking of Bcl-2 by VV-miR-34a increases the release of cytochrome c from mitochondria and then synergistically amplifies the antitumor effects of Smac-induced cell apoptosis. Our study is the first to utilize OVV as the vector for miR-34a or Smac expression to treat MM, and lays the groundwork for future clinical therapy for MM. PMID:27552933

  3. Sensitive determination of neurotransmitters in urine by microchip electrophoresis with multiple-concentration approaches combining field-amplified and reversed-field stacking.

    PubMed

    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. PMID:27187932

  4. Estimating lava volume by precision combination of multiple baseline spaceborne and airborne interferometric synthetic aperture radar: The 1997 eruption of Okmok Volcano, Alaska

    USGS Publications Warehouse

    Lu, Zhiming; Fielding, E.; Patrick, M.R.; Trautwein, C.M.

    2003-01-01

    Interferometric synthetic aperture radar (InSAR) techniques are used to calculate the volume of extrusion at Okmok volcano, Alaska by constructing precise digital elevation models (DEMs) that represent volcano topography before and after the 1997 eruption. The posteruption DEM is generated using airborne topographic synthetic aperture radar (TOPSAR) data where a three-dimensional affine transformation is used to account for the misalignments between different DEM patches. The preeruption DEM is produced using repeat-pass European Remote Sensing satellite data; multiple interferograms are combined to reduce errors due to atmospheric variations, and deformation rates are estimated independently and removed from the interferograms used for DEM generation. The extrusive flow volume associated with the 1997 eruption of Okmok volcano is 0.154 ?? 0.025 km3. The thickest portion is approximately 50 m, although field measurements of the flow margin's height do not exceed 20 m. The in situ measurements at lava edges are not representative of the total thickness, and precise DEM data are absolutely essential to calculate eruption volume based on lava thickness estimations. This study is an example that demonstrates how InSAR will play a significant role in studying volcanoes in remote areas.

  5. Combined expression of miR-34a and Smac mediated by oncolytic vaccinia virus synergistically promote anti-tumor effects in Multiple Myeloma

    PubMed Central

    Lei, Wen; Wang, Shibing; Yang, Chunmei; Huang, Xianbo; Chen, Zhenzhen; He, Wei; Shen, Jianping; Liu, Xinyuan; Qian, Wenbin

    2016-01-01

    Despite great progress made in the treatment of multiple myeloma (MM), it is still incurable. Promising phase II clinical results have been reported recently for oncolytic vaccinia virus (OVV) clinic therapeutics. One reason for this has focused on the critical therapeutic importance of the immune response raised by these viruses. However, few studies have performed their applications as an optimal delivery system for therapeutic gene, especially miRNA in MM. In this study, we constructed two novel OVVs (TK deletion) that express anti-tumor genes, miR-34a and Smac, respectively, in MM cell lines and xenograft model. The results demonstrated that the novel OVV can effectively infect MM cell lines, and forcefully enhance the exogenous gene (miR-34a or Smac) expression. Furthermore, utilization of VV-miR-34a combined with VV-Smac synergistically inhibited tumor growth and induced apoptosis in vitro and in vivo. The underlying mechanism is proposed that blocking of Bcl-2 by VV-miR-34a increases the release of cytochrome c from mitochondria and then synergistically amplifies the antitumor effects of Smac-induced cell apoptosis. Our study is the first to utilize OVV as the vector for miR-34a or Smac expression to treat MM, and lays the groundwork for future clinical therapy for MM. PMID:27552933

  6. Screening of volatile compounds in honey using a new sampling strategy combining multiple extraction temperatures in a single assay by HS-SPME-GC-MS.

    PubMed

    Bianchin, Joyce Nunes; Nardini, Giuliana; Merib, Josias; Dias, Adriana Neves; Martendal, Edmar; Carasek, Eduardo

    2014-02-15

    This paper proposes a new optimization strategy for the extraction of volatile compounds from honey samples using headspace solid-phase microextraction (HS-SPME) and separation/detection by gas chromatography-mass spectrometry (GC-MS). The new optimization strategy was based on the use of three different extraction temperatures in a single assay, aiming at extracting a high number of compounds with wide range of volatilities. As an analytical tool, experimental designs were used for the optimization. The variables extraction time (10-80 min), extraction temperature (0-60 °C), water volume (0.5-5 mL) and percentage of sodium chloride saturation in water (0-100%) were optimised using a five-level fractional central composite design with CAR/DVB/PDMS fibre. The final optimised combination of extraction times at each temperature was 60 min with the sample temperature being held at 60 °C for 36 min, 40 °C for 18 min and 0 °C for 6 min. The proposed method was compared to conventional methods which employ one or two extraction temperatures. It was found that the proposed method presented better results considering the response in terms of the arithmetic means of the peak areas. The use of multiple extraction temperatures for the HS-SPME procedure proved to be an excellent alternative for the screening of compounds present in honey with a wide range of volatilities. PMID:24128584

  7. Quality Evaluation of Scrophulariae Radix Processed by Different 'Sweating' Methods Based on Simultaneous Determination of Multiple Bioactive Constituents Combined with Grey Relational Analysis.

    PubMed

    Wang, Shengnan; Hua, Yujiao; Xu, Li; Zou, Lisi; Liu, Xunhong; Luo, Yiyuan; Liu, Juanxiu; Yan, Ying

    2016-01-01

    Scrophulariae Radix is one of the most popular traditional Chinese medicines (TCMs), which needs to be processed by 'sweating' methods. Primary processing of Scrophulariae Radix is an important link which closely relates to the quality of products in this TCM. To facilitate selection of the suitable 'sweating' processing method for Scrophulariae Radix, in this study the quality of Scrophulariae Radix processed by different 'sweating' methods was evaluated based on simultaneous determination of multiple bioactive constituents combined with grey relational analysis. The contents of iridoid glycosides, phenylpropanoid glycosides, and organic acids in Scrophulariae Radix processed by different 'sweating' methods were simultaneously determined using ultra high performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry (UPLC-QTRAP-MS/MS). Furthermore, grey relational analysis (GRA) was performed to evaluate the 'sweating' processed samples according to the contents of twelve constituents. All of the results demonstrated that the quality of Scrophulariae Radix processed by oven drying at 35 °C and 'sweating' for three days was better. The developed method was useful for the overall assessment on quality of Scrophulariae Radix, and this study may provide the foundation and support for 'sweating' processing of Scrophulariae Radix in normalization and standardization. PMID:27367656

  8. 3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

    NASA Astrophysics Data System (ADS)

    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.

  9. Sensitive determination of neurotransmitters in urine by microchip electrophoresis with multiple-concentration approaches combining field-amplified and reversed-field stacking.

    PubMed

    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.

  10. Combined exercise training reduces fatigue and modulates the cytokine profile of T-cells from multiple sclerosis patients in response to neuromediators.

    PubMed

    Alvarenga-Filho, Helcio; Sacramento, Priscila M; Ferreira, Thais B; Hygino, Joana; Abreu, Jorge Eduardo Canto; Carvalho, Sonia Regina; Wing, Ana Cristina; Alvarenga, Regina Maria Papais; Bento, Cleonice A M

    2016-04-15

    Fatigue is a common and disabling symptom of multiple sclerosis (MS), a classical Th1- and Th17-mediated autoimmune disease. There is no effective pharmacological treatment for fatigue, but some reports point towards beneficial effects of physical activity on management of the fatigue in MS patients. As both MS and fatigue have been associated with dysregulated cytokine network production, the objective of the present study was to evaluate the impact of a physical activity program consisting of a 12-week series of combining Pilates and aerobic exercises on fatigue severity, determined by FSS, and cytokine production, quantified by ELISA, by T cells from MS patients (n=08) with low disability (EDSS≤2). The results showed decrease in FSSs in all patients at the end of physical activity intervention. Regarding the cytokines, a significant reduction of IL-22 release was observed in polyclonally-activated T cells form MS patients post-training follow-up. Interestingly, while the physical activity attenuated the ability of dopamine in up-regulating Th17-related cytokines, it enhanced the anti-inflammatory effects of serotonin, evidenced by high IL-10 production. In summary, all results suggest that programmed physical activity has beneficial effects on management of fatigue in MS patients, and it could be related, at least in part, to its ability in regulating neuroimmune parameters into T cell compartment. PMID:27049568

  11. Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients.

    PubMed

    de Waal, Esther G M; de Munck, Linda; Hoogendoorn, Mels; Woolthuis, Gerhard; van der Velden, Annette; Tromp, Yvonne; Vellenga, Edo; Hovenga, Sjoerd

    2015-12-01

    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 bortezomib and cyclophosphamide. Relapsed MM patients were treated with six cycles of bortezomib twice weekly, cyclophosphamide 50 mg daily and dexamethasone. Maintenance therapy was given for 1 year. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression-free (PFS) and overall survival (OS). This study included 59 patients. Myelosuppression and neuropathy were the most common side effects. Median follow-up was 27·1 (0·46-54·4) months with an overall response of 71%, and a very good partial response or more of 33%. During maintenance, improved responsiveness was observed in 19% of the patients. The median PFS was 18·4 months (range 0·13-43·5) and the median OS was 28·1 months (range 0·13-54·4). In conclusion, our study demonstrates that treatment with bortezomib, dexamethasone and low-dose cyclophosphamide is an effective and manageable regimen. Adding 1 year of maintenance was feasible, with limited side effects and an increased response rate.

  12. Some thoughts on error-contributions to reconstruct 3D coseismic displacement field using the model of combining multiple independent InSAR

    NASA Astrophysics Data System (ADS)

    Liu, Bin; Zhang, Jingfa; Luo, Yi

    2012-07-01

    Interferometric Synthetic Aperture Radar (InSAR) has proved an immensely powerful tool in studying earthquakes with millimetre-scale accuracy at a high spatial resolution. However, each interferogram records only the component of displacement in the direction of the satellite line of sight (LOS). Thus previous InSAR studies of displacement due to earthquakes were generally limited to one or two components of the surface displacement field. Three- dimensional (3D) surface displacement maps can provide a more comprehensive understanding of source geometry associated with earthquake. By combining interferograms from multiple look angles, it is possible to constrain the three-dimensional components of displacement [Jung et al., 2011; Wright, et al., 2004; Hong et al., 2010]. In this work, we take 2008 Gaize Ms6.9 earthquake (Tibet) for example, derive LOS surface displacement from several paths of ENVISAT ASAR images (Image mode: Track 348, descending pass; Track 341, 427, and 155, ascending pass. ScanSAR mode: Track 341, 112, 155, and 384, ascending pass), and reconstruct the 3D coseismic displacement field with the model named multiple independent InSAR with different viewing angles. Because it is difficult to distinguish tectonic signal from phase noise (eg. orbital errors, atmospheric errors, and unwrapping errors), these error-contributions may be propagated to the 3D coseismic components (vertical, north, east). In addition, for ENVISAT ASAR, it is worth notice that the radar antenna is fixed with respect to the current satellite, which may lead to different LOS observations with nearly identical viewing angles in parallel passes. Thus, when inverting 3D components with least square solution, InSAR observation errors may be magnified by the ill-conditioned system of equations in the solution. Although the ill-conditioned system of equations may result in bad solution, some InSAR observation errors can be detected by the system. In our study, we will introduce the

  13. Enhanced anticancer efficacy of snake venom combined with silica nanoparticles in a murine model of human multiple myeloma: molecular targets for cell cycle arrest and apoptosis induction.

    PubMed

    Al-Sadoon, Mohamed K; Rabah, Danny M; Badr, Gamal

    2013-01-01

    Multiple myeloma (MM) is a clonal disease of plasma cells that reside in the bone marrow (BM). MM is an incurable disease; thus, screening for novel anti-myeloma drugs remains critically important. We recently described a silica nanoparticle-based snake venom delivery model that targets cancer cells, but not normal cells. Using this model, we demonstrated a strong enhancement of the antitumor activity of snake venom extracted from Walterinnesia aegyptia (WEV) in two breast carcinoma cell lines when the venom was combined with silica nanoparticles (WEV+NP). In the present study, we aimed to delineate the in vivo therapeutic efficacy of WEV+NP in an MM-bearing experimental nude mouse model. We found that treatment with WEV+NP or WEV alone significantly inhibited tumor growth compared to treatment with NP or vehicle. WEV+NP- and WEV-treated cancer cells exhibited marked elevations in oxidative stress and robust reductions in the levels of interleukin-6 (IL-6) and B cell-activating factor (BAFF). WEV+NP also decreased the surface expression of the chemokine receptors CXCR3, CXCR4 and CXCR6 to a greater extent than WEV alone, and WEV+NP subsequently reduced migration in response to the cognate ligands CXCL10, CXCL12 and CXCL16. Furthermore, we found that WEV+NP strongly inhibited insulin-like growth factor 1 (EGF-1)- and IL-6-mediated MM cell proliferation, altered the cell cycle and enhanced the induction of apoptosis of MM cells. In addition, the results of treatment with WEV+NP or WEV alone revealed that the combination of WEV with NP robustly decreased the expression of cyclin D1, Bcl-2 and the phosphorylation of AKT; increased the expression of cyclin B1; altered the mitochondrial membrane potential; increased the activity of caspase-3, -8 and -9; and sensitized MM cells to growth arrest and apoptosis. Our data reveal the therapeutic potential of the nanoparticle-sustained delivery of snake venom to fight cancer cells. PMID:23973876

  14. Enhanced anticancer efficacy of snake venom combined with silica nanoparticles in a murine model of human multiple myeloma: molecular targets for cell cycle arrest and apoptosis induction.

    PubMed

    Al-Sadoon, Mohamed K; Rabah, Danny M; Badr, Gamal

    2013-01-01

    Multiple myeloma (MM) is a clonal disease of plasma cells that reside in the bone marrow (BM). MM is an incurable disease; thus, screening for novel anti-myeloma drugs remains critically important. We recently described a silica nanoparticle-based snake venom delivery model that targets cancer cells, but not normal cells. Using this model, we demonstrated a strong enhancement of the antitumor activity of snake venom extracted from Walterinnesia aegyptia (WEV) in two breast carcinoma cell lines when the venom was combined with silica nanoparticles (WEV+NP). In the present study, we aimed to delineate the in vivo therapeutic efficacy of WEV+NP in an MM-bearing experimental nude mouse model. We found that treatment with WEV+NP or WEV alone significantly inhibited tumor growth compared to treatment with NP or vehicle. WEV+NP- and WEV-treated cancer cells exhibited marked elevations in oxidative stress and robust reductions in the levels of interleukin-6 (IL-6) and B cell-activating factor (BAFF). WEV+NP also decreased the surface expression of the chemokine receptors CXCR3, CXCR4 and CXCR6 to a greater extent than WEV alone, and WEV+NP subsequently reduced migration in response to the cognate ligands CXCL10, CXCL12 and CXCL16. Furthermore, we found that WEV+NP strongly inhibited insulin-like growth factor 1 (EGF-1)- and IL-6-mediated MM cell proliferation, altered the cell cycle and enhanced the induction of apoptosis of MM cells. In addition, the results of treatment with WEV+NP or WEV alone revealed that the combination of WEV with NP robustly decreased the expression of cyclin D1, Bcl-2 and the phosphorylation of AKT; increased the expression of cyclin B1; altered the mitochondrial membrane potential; increased the activity of caspase-3, -8 and -9; and sensitized MM cells to growth arrest and apoptosis. Our data reveal the therapeutic potential of the nanoparticle-sustained delivery of snake venom to fight cancer cells.

  15. The clinical activity of arsenic trioxide, ascorbic acid, ifosfamide and prednisone combination therapy in patients with relapsed and refractory multiple myeloma

    PubMed Central

    Li, Xin; Sun, Wan-Jun

    2015-01-01

    This study aimed to investigate the activity of arsenic trioxide (As2O3) combined with ascorbic acid, ifosfamide, and prednisone chemotherapy in patients with repeatedly relapsed and refractory multiple myeloma (MM). Here, we retrospectively analyzed medical data of 30 MM patients showing progressive disease after receiving at least two previous lines of treatment including an immunomodulatory agent (thalidomide or lenalidomide) and a proteasome inhibitor. There were 19 men and eleven women, aged 54–73 (median 65) years, in this study. The distribution of different isotypes included immunoglobulin G(IgG) (12 patients), IgA (six patients), IgD (three), and light chain (nine patients). All the patients were Durie–Salmon stage III and had relapsed at least three times; the median cycles of prior therapies was 15 (range 10–18). The patients were treated with As2O3, ascorbic acid, and CP (ifosfamide 1 g on day 1, day 3, day 5, and day 7; prednisone 30 mg taken orally for 2 weeks). As2O3 was administered as an intravenous infusion at a dose of 10 mg/d and ascorbic acid at a dose of 2 g/d for 14 days of each 4-week cycle. The results showed that after 2 cycles of therapy, there were five patients that attained partial response, 15 had minimal response, five had no change, and five had progressive disease. The overall response rate was 66.7% (20/30 cases), 50% (10/20 cases), and 40% (2/5 cases), respectively, after 2, 4, and 6 cycles of the therapy. But there were no patients that attained complete remission. The median time of overall survival and progression-free survival were 48 (29–120) and 6 (2–8) months, respectively. The most common treatment-related adverse events included neutropenia, fatigue, anemia, thrombocytopenia, and infection that could be tolerated. The results showed that As2O3 combined with ascorbic acid, ifosfamide, and prednisone chemotherapy may be a choice treatment for repeatedly relapsed and refractory MM patients. PMID:25914547

  16. Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries.

    PubMed

    Jehee, Fernanda Sarquis; Takamori, Jean Tetsuo; Medeiros, Paula F Vasconcelos; Pordeus, Ana Carolina B; Latini, Flavia Roche M; Bertola, Débora Romeo; Kim, Chong Ae; Passos-Bueno, Maria Rita

    2011-01-01

    Conventional karyotyping detects anomalies in 3-15% of patients with multiple congenital anomalies and mental retardation (MCA/MR). Whole-genome array screening (WGAS) has been consistently suggested as the first choice diagnostic test for this group of patients, but it is very costly for large-scale use in developing countries. We evaluated the use of a combination of Multiplex Ligation-dependent Probe Amplification (MLPA) kits to increase the detection rate of chromosomal abnormalities in MCA/MR patients. We screened 261 MCA/MR patients with two subtelomeric and one microdeletion kits. This would theoretically detect up to 70% of all submicroscopic abnormalities. Additionally we scored the de Vries score for 209 patients in an effort to find a suitable cut-off for MLPA screening. Our results reveal that chromosomal abnormalities were present in 87 (33.3%) patients, but only 57 (21.8%) were considered causative. Karyotyping detected 15 abnormalities (6.9%), while MLPA identified 54 (20.7%). Our combined MLPA screening raised the total detection number of pathogenic imbalances more than three times when compared to conventional karyotyping. We also show that using the de Vries score as a cut-off for this screening would only be suitable under financial restrictions. A decision analytic model was constructed with three possible strategies: karyotype, karyotype + MLPA and karyotype + WGAS. Karyotype + MLPA strategy detected anomalies in 19.8% of cases which account for 76.45% of the expected yield for karyotype + WGAS. Incremental Cost Effectiveness Ratio (ICER) of MLPA is three times lower than that of WGAS, which means that, for the same costs, we have three additional diagnoses with MLPA but only one with WGAS. We list all causative alterations found, including rare findings, such as reciprocal duplications of regions deleted in Sotos and Williams-Beuren syndromes. We also describe imbalances that were considered polymorphisms or rare variants, such as the new SNP

  17. A Sativex®-like combination of phytocannabinoids as a disease-modifying therapy in a viral model of multiple sclerosis

    PubMed Central

    Feliú, A; Moreno-Martet, M; Mecha, M; Carrillo-Salinas, F J; de Lago, E; Fernández-Ruiz, J; Guaza, C

    2015-01-01

    Background and Purpose Sativex® is an oromucosal spray, containing equivalent amounts of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD)-botanical drug substance (BDS), which has been approved for the treatment of spasticity and pain associated to multiple sclerosis (MS). In this study, we investigated whether Sativex may also serve as a disease-modifying agent in the Theiler's murine encephalomyelitis virus-induced demyelinating disease model of MS. Experimental Approach A Sativex-like combination of phytocannabinoids and each phytocannabinoid alone were administered to mice once they had established MS-like symptoms. Motor activity and the putative targets of these cannabinoids were assessed to evaluate therapeutic efficacy. The accumulation of chondroitin sulfate proteoglycans (CSPGs) and astrogliosis were assessed in the spinal cord and the effect of Sativex on CSPGs production was evaluated in astrocyte cultures. Key Results Sativex improved motor activity – reduced CNS infiltrates, microglial activity, axonal damage – and restored myelin morphology. Similarly, we found weaker vascular cell adhesion molecule-1 staining and IL-1β gene expression but an up-regulation of arginase-1. The astrogliosis and accumulation of CSPGs in the spinal cord in vehicle-infected animals were decreased by Sativex, as was the synthesis and release of CSPGs by astrocytes in culture. We found that CBD-BDS alone alleviated motor deterioration to a similar extent as Sativex, acting through PPARγ receptors whereas Δ9-THC-BDS produced weaker effects, acting through CB2 and primarily CB1 receptors. Conclusions and Implications The data support the therapeutic potential of Sativex to slow MS progression and its relevance in CNS repair. PMID:25857324

  18. Validation of web-based, multiple 24-h recalls combined with nutritional supplement intake questionnaires against nitrogen excretions to determine protein intake in Dutch elite athletes.

    PubMed

    Wardenaar, F C; Steennis, J; Ceelen, I J M; Mensink, M; Witkamp, R; de Vries, J H M

    2015-12-28

    Information on dietary composition is vitally important for elite athletes to optimise their performance and recovery, which requires valid tools. The aim of the present study was to investigate the validity of assessing protein intake using three web-based 24-h recalls and questionnaires, by comparing these with three urinary N excretions on the same day. A total of forty-seven Dutch elite top athletes, both disabled and non-disabled, aged between 18 and 35 years, with a BMI of 17·5-31 kg/m2, exercising >12 h/week were recruited. Estimated mean dietary protein intake was 109·6 (sd 33·0) g/d by recalls and questionnaires v. 141·3 (sd 38·2) g/d based on N excretions in urine; the difference was 25·5 (sd 21·3) % between the methods (P<0·05). We found a reasonably good association between methods for protein intake of 0·65 (95 % CI 0·45, 0·79). On an individual level, under-reporting was larger with higher protein intakes than with lower intakes. No significant differences were found in reporting absolute differences between subcategories (sex, under-reporting, BMI, collection of recalls within a certain amount of time and using protein supplements or not). In conclusion, combined, multiple, 24-h recalls and questionnaires underestimated protein intake in these young elite athletes more than that reported for non-athlete populations. The method proved to be suitable for ranking athletes according to their protein intake as needed in epidemiological studies. On an individual level, the magnitude of underestimation was about equal for all athletes except for those with very high protein intakes.

  19. Mechanistic insight into neurotoxicity of tissue plasminogen activator-induced thrombolysis products in a rat intraluminal middle cerebral artery occlusion model.

    PubMed

    Oka, Fumiaki; Fujisawa, Hirosuke; Nomura, Sadahiro; Kajiwara, Koji; Kato, Shoichi; Fujii, Masami; Izuma, Hiroshi; Uozumi, Kanako; Gondo, Toshikazu; Suzuki, Michiyasu

    2009-09-01

    Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) after ischemic stroke is effective. However, rtPA potentiates neuronal damage, and interactions between rtPA and thrombolysis products (TLP) have been reported to play a role in this. In the present study we investigated the mechanisms underlying rtPA- and TLP-induced neurotoxicity. Adult male Sprague-Dawley rats were subjected to 60-min intraluminal middle cerebral artery (MCA) occlusion, and then treated with rtPA (10 mg/kg), TLP, or saline. To evaluate the effects of a free radical scavenger, treatment with edaravone and TLP was evaluated. To investigate the role of red blood cells (RBCs), RBC-depleted TLP was used. Neurological deficit scores, infarct volume, and immuno-histochemical localization of oxidative end products for lipid and DNA (4-hydroxy-2-nonenal [4-HNE] and 8-hydroxy-deoxyguanosine [8-OHdG]) were evaluated. TLP increased the infarct volume, worsened the neurological deficits, and increased accumulations of 4-HNE and 8-OHdG. Edaravone treatment significantly reduced the lesion volume and improved the neurological score. Both infarct volume and accumulation of oxidative products were significantly suppressed when RBC-depleted TLP was used. In this mechanical model of MCA occlusion, rtPA-induced TLP, especially in the presence of RBCs, contributed to neuronal damage by accelerating free radical injury.

  20. 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

    ERIC Educational Resources Information Center

    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,…

  1. Can You Know Me Better? An Exploratory Study Combining Behavioural and Physiological Measurements for an Objective Assessment of Sensory Responsiveness in a Child with Profound Intellectual and Multiple Disabilities

    ERIC Educational Resources Information Center

    Lima, Mariely; Silva, Karine; Magalhaes, Ana; Amaral, Isabel; Pestana, Helena; de Sousa, Liliana

    2012-01-01

    Background: Sensory assessment of individuals with profound intellectual and multiple disabilities (PIMD) can be difficult for several reasons, including the idiosyncratic reactions that these individuals exhibit to environmental stimuli. This case report presents a combination of behavioural and physiological measurements aimed at providing an…

  2. Comparison Study of Polysomnographic Features in Multiple System Atrophy-cerebellar Types Combined with and without Rapid Eye Movement Sleep Behavior Disorder

    PubMed Central

    Ding, Yan; Hu, Yue-Qing; Zhan, Shu-Qin; Li, Cun-Jiang; Wang, Hong-Xing; Wang, Yu-Ping

    2016-01-01

    Background: The brain stem is found to be impaired in multiple system atrophy-cerebellar types (MSA-C). Rapid eye movement (REM) sleep behavior disorder (RBD) is reported as a marker of progressive brain stem dysfunction. Few systematic studies about the sleep disturbances in MSA-C patients combined with or without RBD were reported. This study aimed to explore the polysomnographic (PSG) features of sleep disturbances between MSA-C patients with and without RBD. Methods: Totally, 46 MSA-C patients (23 with RBD, and 23 without RBD) were enrolled in this study. All patients underwent a structured interview for their demographic data, history of sleep pattern, and movement disorders; and then, overnight video-PSG was performed in each patient. All the records were evaluated by specialists at the Sleep Medicine Clinic for RBD and the Movement Disorder Clinic for MSA-C. The Student's t-test, Mann-Whitney U-test for continuous variables, and the Chi-square test for categorical variables were used in this study. Results: MSA-C patients with RBD had younger visiting age (52.6 ± 7.4 vs. 56.7 ± 6.0 years, P = 0.046) and shorter duration of the disease (12.0 [12.0, 24.0] vs. 24.0 [14.0, 36.0] months, P = 0.009) than MSA-C patients without RBD. MSA-C with RBD had shorter REM sleep latency (111.7 ± 48.2 vs. 157.0 ± 68.8 min, P = 0.042), higher percentage of REM sleep (14.9% ±4.0% vs. 10.0% ± 3.2%, P = 0.019), and lower Stage I (9.5% ±7.2% vs. 15.9% ±8.0%, P = 0.027) than MSA-C without RBD. Moreover, MSA-C patients with RBD had more decreased sleep efficiency (52.4% ±12.6% vs. 65.8% ±15.9%, P = 0.029) than that without RBD. Conclusions: In addition to the RBD, MSA-C patients with RBD had other more severe sleep disturbances than those without RBD. The sleep disorders of MSA patients might be associated with the progress of the disease. PMID:27625088

  3. A Real-Time Clinical Endoscopic System for Intraluminal, Multiplexed Imaging of Surface-Enhanced Raman Scattering Nanoparticles

    PubMed Central

    Garai, Ellis; Loewke, Nathan O.; Rogalla, Stephan; Mandella, Michael J.; Felt, Stephen A.; Friedland, Shai; Liu, Jonathan T. C.; Gambhir, Sanjiv S.; Contag, Christopher H.

    2015-01-01

    The detection of biomarker-targeting surface-enhanced Raman scattering (SERS) nanoparticles (NPs) in the human gastrointestinal tract has the potential to improve early cancer detection; however, a clinically relevant device with rapid Raman-imaging capability has not been described. Here we report the design and in vivo demonstration of a miniature, non-contact, opto-electro-mechanical Raman device as an accessory to clinical endoscopes that can provide multiplexed molecular data via a panel of SERS NPs. This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present. Human and swine studies have demonstrated the speed and simplicity of this technique. This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs. Therefore, this new screening strategy has the potential to improve diagnosis and to guide therapy by enabling sensitive quantitative molecular detection of small and otherwise hard-to-detect lesions in the context of white-light endoscopy. PMID:25923788

  4. Impact of Intraluminal Brachytherapy on Survival Outcome for Radiation Therapy for Unresectable Biliary Tract Cancer: A Propensity-Score Matched-Pair Analysis

    SciTech Connect

    Yoshioka, Yasuo; Ogawa, Kazuhiko; Oikawa, Hirobumi; Onishi, Hiroshi; Kanesaka, Naoto; Tamamoto, Tetsuro; Kosugi, Takashi; Hatano, Kazuo; Kobayashi, Masao; Ito, Yoshinori; Takayama, Makoto; Takemoto, Mitsuhiro; Karasawa, Katsuyuki; Nagakura, Hisayasu; Imai, Michiko; Kosaka, Yasuhiro; Yamazaki, Hideya; Isohashi, Fumiaki; Nemoto, Kenji; Nishimura, Yasumasa

    2014-07-15

    Purpose: To determine whether adding intraluminal brachytherapy (ILBT) to definitive radiation therapy (RT) for unresectable biliary tract cancer has a positive impact on survival outcome. Methods and Materials: The original cohort comprised 209 patients, including 153 who underwent external beam RT (EBRT) alone and 56 who received both ILBT and EBRT. By matching propensity scores, 56 pairs (112 patients) consisting of 1 patient with and 1 patient without ILBT were selected. They were well balanced in terms of sex, age, performance status, clinical stage, jaundice, and addition of chemotherapy. The impact of ILBT on overall survival (OS), disease-specific survival (DSS), and local control (LC) was investigated. Results: The 2-year OS rates were 31% for the ILBT+ group and 40% for theILBT– group (P=.862). The 2-year DSS rates were 42% for the ILBT+ group and 41% for the ILBT– group (P=.288). The 2-year LC rates were 65% for the ILBT+ group and 35% for the ILBT– group (P=.094). Three of the 4 sensitivity analyses showed a significantly better LC for the ILBT+ group (P=.010, .025, .049), and another showed a marginally better LC (P=.068), and none of the sensitivity analyses showed any statistically significant differences in OS or DSS. Conclusions: In the treatment for unresectable biliary tract cancer, the addition of ILBT to RT has no impact on OS or DSS but is associated with better LC. Therefore, the role of ILBT should be addressed by other measures than survival benefit, for example, by less toxicity, prolonged biliary tract patency decreasing the need for further palliative interventions, or patient quality of life.

  5. Multiple drug therapy--a comparative study with 2 tier and 3 tier combination of rifampicin, clofazimine, DDS, INAH and thiacetazone in lepromatous cases.

    PubMed

    Kundu, S K; Ghosh, S; Hazra, S; Chaudhury, S

    1981-04-01

    A comparative study with 2 tier and 3 tier combination of Rifampicin, Clofazimine, DDS, INAH and Thiacetazone was conducted on fifty lepromatous leprosy cases for varying periods. Assessment showed that 2 tier combination of clofazimine and DDS produced good results but the cost stood in the way; whereas 3 tier combination of DDS, thiacetazone and INAH also yielded good results with much less expenses to be incurred by the patients. Whether therapy with this 3 tier combination could be continued for a longer period with sustained improvement is yet to be assessed by further studies for a considerable period.

  6. The Single and Combined Effects of Multiple Intensities of Behavior Modification and Methylphenidate for Children with Attention Deficit Hyperactivity Disorder in a Classroom Setting

    ERIC Educational Resources Information Center

    Fabiano, Gregory A.; Pelham, William E., Jr.; Gnagy, Elizabeth M.; Burrows-MacLean, Lisa; Coles, Erika K.; Chacko, Anil; Wymbs, Brian T.; Walker, Kathryn S.; Arnold, Fran; Garefino, Allison; Keenan, Jenna K.; Onyango, Adia N.; Hoffman, Martin T.; Massetti, Greta M.; Robb, Jessica A.

    2007-01-01

    Currently behavior modification, stimulant medication, and combined treatments are supported as evidence-based interventions for attention deficit hyperactivity disorder in classroom settings. However, there has been little study of the relative effects of these two modalities and their combination in classrooms. Using a within-subject design, the…

  7. 5 CFR 591.216 - How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS ALLOWANCES AND DIFFERENTIALS Cost-of... equal weights to compute an overall average by item for the DC area. (b) COLA areas with multiple survey... corresponding indexes and Federal employment weights from each survey area within the COLA area....

  8. A method for the study of the effects of combining multiple pseudorandom fusimotor stimulation on the responses of muscle-spindle primary-ending afferents.

    PubMed

    Hulliger, Manuel; Banks, Robert W

    2009-03-30

    We describe a new method of investigation of the integrative action of fusimotor inputs in mammalian muscle spindles by stimulation of multiple fusimotor axons using independent pseudorandom pulse trains, each of low mean rate with pseudorandomly distributed stimulus intervals. Technically it was feasible only because of the development of (1) a novel, highly efficient approach to functional isolation of fusimotor efferents in ventral-root filaments, which we have called the isodyne strategy; (2) a real-time, microprocessor-based stimulus artefact cancellation device (SACAD); and (3) a highly adjustable, multi-branch stimulation electrode array. The general approach of using multiple, independent, pseudorandom stimulation of several input channels has wider applications in controlled-activation paradigms. PMID:19109995

  9. Combined action of time-delay and colored cross-associated multiplicative and additive noises on stability and stochastic resonance for a stochastic metapopulation system

    NASA Astrophysics Data System (ADS)

    Wang, Kang-Kang; Zong, De-Cai; Wang, Ya-Jun; Li, Sheng-Hong

    2016-05-01

    In this paper, the transition between the stable state of a big density and the extinction state and stochastic resonance (SR) for a time-delayed metapopulation system disturbed by colored cross-correlated noises are investigated. By applying the fast descent method, the small time-delay approximation and McNamara and Wiesenfeld's SR theory, we investigate the impacts of time-delay, the multiplicative, additive noises and colored cross-correlated noise on the SNR and the shift between the two states of the system. Numerical results show that the multiplicative, additive noises and time-delay can all speed up the transition from the stable state to the extinction state, while the correlation noise and its correlation time can slow down the extinction process of the population system. With respect to SNR, the multiplicative noise always weakens the SR effect, while noise correlation time plays a dual role in motivating the SR phenomenon. Meanwhile, time-delay mainly plays a negative role in stimulating the SR phenomenon. Conversely, it could motivate the SR effect to increase the strength of the cross-correlation noise in the SNR-β plot, while the increase of additive noise intensity will firstly excite SR, and then suppress the SR effect.

  10. Myeloma (multiple)

    PubMed Central

    2006-01-01

    Introduction Multiple myeloma is the most common primary cancer of the bones in adults, representing about 1% of all cancers diagnosed in the US in 2004, and 14% of all haematological malignancies. In the UK, multiple myeloma accounts for 1% of all new cases of cancer diagnosed each year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment in people with asymptomatic early stage multiple myeloma (stage I)? What are the effects of first-line treatments in people with advanced stage multiple myeloma (stages II and III)? What are the effect of salvage treatments, or supportive therapy, in people with advanced stage multiple myeloma (stages II and III)? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2004 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: allogenic transplant (non-myeloablative), autologous stem cell transplant (early or late transplantation, double or single, purging of), bisphosphonates, bone marrow stem cells, bortezomib, chemotherapy (combination, conventional dose, intermediate dose plus stem cell rescue, high-dose plus stem cell rescue), combination chemotherapy plus corticosteroids, deferred treatment (in stage I disease), early chemotherapy plus corticosteroids (in stage I disease), epoetin alpha, first-line treatments, infection prophylaxis, interferon, maintenance therapy (in advanced multiple myeloma), melphalan (normal dose

  11. Predictive thermal inactivation model for the combined effect of temperature, cinnamaldehyde and carvacrol on starvation-stressed multiple Salmonella serotypes in ground chicken

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated the combined effect of three internal temperatures (60, 65 and 71.1C) and four concentrations (0.0, 0.1, 0.5 and 1% vol/wt) of two natural antimicrobials on the heat resistance of an eight-strain cocktail of Salmonella serovars in chicken meat. A complete factorial design (3 x 4 x 4...

  12. Interstitial deletions of the short arm of chromosome 4 in patients with a similar combination of multiple minor anomalies and mental retardation

    SciTech Connect

    White, D.M.; Pillers, D.A.M.; Magenis, R.E.

    1995-07-17

    Interstitial deletions of chromosome 4 have been described rarely and have had variable presentations. We describe the phenotypic characteristics associated with interstitial deletion of the p14-16 region of chromosome 4 in 7 patients with multiple minor anomalies in common, and with mental retardation. A review of published cases of interstitial deletions of the short arm of chromosome 4 is provided. These deletions present a distinct phenotype which is different from that of Wolf-Hirschhorn syndrome. 52 refs., 12 figs., 2 tabs.

  13. Combining cluster analysis, feature selection and multiple support vector machine models for the identification of human ether-a-go-go related gene channel blocking compounds.

    PubMed

    Nisius, Britta; Göller, Andreas H; Bajorath, Jürgen

    2009-01-01

    Blockade of the human ether-a-go-go related gene potassium channel is regarded as a major cause of drug toxicity and associated with severe cardiac side-effects. A variety of in silico models have been reported to aid in the identification of compounds blocking the human ether-a-go-go related gene channel. Herein, we present a classification approach for the detection of diverse human ether-a-go-go related gene blockers that combines cluster analysis of training data, feature selection and support vector machine learning. Compound learning sets are first divided into clusters of similar molecules. For each cluster, independent support vector machine models are generated utilizing preselected MACCS structural keys as descriptors. These models are combined to predict human ether-a-go-go related gene inhibition of our large compound data set with consistent experimental measurements (i.e. only patch clamp measurements on mammalian cell lines). Our combined support vector machine model achieves a prediction accuracy of 85% on this data set and performs better than alternative methods used for comparison. We also find that structural keys selected on the basis of statistical criteria are associated with molecular substructures implicated in human ether-a-go-go related gene channel binding.

  14. Vitamin E analog, alpha-tocopherol ether-linked acetic acid analog, alone and in combination with celecoxib, reduces multiplicity of ultraviolet-induced skin cancers in mice.

    PubMed

    Riedel, Shelley B; Fischer, Susan M; Sanders, Bob G; Kline, Kimberly

    2008-02-01

    The goals of this study were to determine whether alpha-tocopherol ether-linked acetic acid analog (alpha-TEA), a novel vitamin E analog, and celecoxib, alone or in combination, when administered as a late intervention can reduce the ultraviolet-induced nonmelanoma skin-tumor burden of established tumors, prevent additional tumors from developing, and prevent tumor recurrence once treatments are stopped. Hairless SKH-1 female mice were ultraviolet-irradiated for 24 weeks, divided into treatment groups so that each group had approximately 5.8 tumors/mouse, and then treated with 72 mug of liposome-formulated alpha-TEA by aerosol inhalation, 500 p.p.m. celecoxib in AIN-76 A diet, or a combination of alpha-TEA and celecoxib for 4 weeks. At the end of 4 weeks of treatment, each treatment group was subdivided, with one subgroup continuing to receive treatment and with treatment being stopped in the other. Skin-tumor development was monitored visually throughout the study and by histologic evaluation at the end. After 4 weeks of treatment, all treatments showed statistically significant reductions in tumor number when compared with controls. After termination of treatment, only alpha-TEA prevented a significant increase in tumor recurrence; however, continuous combination treatment resulted in the lowest total number of tumors. In conclusion alpha-TEA is an effective late-stage chemopreventive agent for nonmelanoma skin cancer that exhibits lasting benefits.

  15. KeyPathwayMiner 4.0: condition-specific pathway analysis by combining multiple omics studies and networks with Cytoscape

    PubMed Central

    2014-01-01

    Background Over the last decade network enrichment analysis has become popular in computational systems biology to elucidate aberrant network modules. Traditionally, these approaches focus on combining gene expression data with protein-protein interaction (PPI) networks. Nowadays, the so-called omics technologies allow for inclusion of many more data sets, e.g. protein phosphorylation or epigenetic modifications. This creates a need for analysis methods that can combine these various sources of data to obtain a systems-level view on aberrant biological networks. Results We present a new release of KeyPathwayMiner (version 4.0) that is not limited to analyses of single omics data sets, e.g. gene expression, but is able to directly combine several different omics data types. Version 4.0 can further integrate existing knowledge by adding a search bias towards sub-networks that contain (avoid) genes provided in a positive (negative) list. Finally the new release now also provides a set of novel visualization features and has been implemented as an app for the standard bioinformatics network analysis tool: Cytoscape. Conclusion With KeyPathwayMiner 4.0, we publish a Cytoscape app for multi-omics based sub-network extraction. It is available in Cytoscape’s app store http://apps.cytoscape.org/apps/keypathwayminer or via http://keypathwayminer.mpi-inf.mpg.de. PMID:25134827

  16. Combination of a Selective HSP90α/β Inhibitor and a RAS-RAF-MEK-ERK Signaling Pathway Inhibitor Triggers Synergistic Cytotoxicity in Multiple Myeloma Cells

    PubMed Central

    Mimura, Naoya; Minami, Jiro; Ohguchi, Hiroto; Yoshida, Yasuhiro; Sagawa, Morihiko; Gorgun, Gullu; Cirstea, Diana; Cottini, Francesca; Jakubikova, Jana; Tai, Yu-Tzu; Chauhan, Dharminder; Richardson, Paul G.; Munshi, Nikhil; Ando, Kiyoshi; Utsugi, Teruhiro; Hideshima, Teru; Anderson, Kenneth C.

    2015-01-01

    Heat shock protein (HSP)90 inhibitors have shown significant anti-tumor activities in preclinical settings in both solid and hematological tumors. We previously reported that the novel, orally available HSP90α/β inhibitor TAS-116 shows significant anti-MM activities. In this study, we further examined the combination effect of TAS-116 with a RAS-RAF-MEK-ERK signaling pathway inhibitor in RAS- or BRAF-mutated MM cell lines. TAS-116 monotherapy significantly inhibited growth of RAS-mutated MM cell lines and was associated with decreased expression of downstream target proteins of the RAS-RAF-MEK-ERK signaling pathway. Moreover, TAS-116 showed synergistic growth inhibitory effects with the farnesyltransferase inhibitor tipifarnib, the BRAF inhibitor dabrafenib, and the MEK inhibitor selumetinib. Importantly, treatment with these inhibitors paradoxically enhanced p-C-Raf, p-MEK, and p-ERK activity, which was abrogated by TAS-116. TAS-116 also enhanced dabrafenib-induced MM cytotoxicity associated with mitochondrial damage-induced apoptosis, even in the BRAF-mutated U266 MM cell line. This enhanced apoptosis in RAS-mutated MM triggered by combination treatment was observed even in the presence of bone marrow stromal cells. Taken together, our results provide the rationale for novel combination treatment with HSP90α/β inhibitor and RAS-RAF-MEK-ERK signaling pathway inhibitors to improve outcomes in patients with in RAS- or BRAF-mutated MM. PMID:26630652

  17. Combination of a Selective HSP90α/β Inhibitor and a RAS-RAF-MEK-ERK Signaling Pathway Inhibitor Triggers Synergistic Cytotoxicity in Multiple Myeloma Cells.

    PubMed

    Suzuki, Rikio; Kikuchi, Shohei; Harada, Takeshi; Mimura, Naoya; Minami, Jiro; Ohguchi, Hiroto; Yoshida, Yasuhiro; Sagawa, Morihiko; Gorgun, Gullu; Cirstea, Diana; Cottini, Francesca; Jakubikova, Jana; Tai, Yu-Tzu; Chauhan, Dharminder; Richardson, Paul G; Munshi, Nikhil; Ando, Kiyoshi; Utsugi, Teruhiro; Hideshima, Teru; Anderson, Kenneth C

    2015-01-01

    Heat shock protein (HSP)90 inhibitors have shown significant anti-tumor activities in preclinical settings in both solid and hematological tumors. We previously reported that the novel, orally available HSP90α/β inhibitor TAS-116 shows significant anti-MM activities. In this study, we further examined the combination effect of TAS-116 with a RAS-RAF-MEK-ERK signaling pathway inhibitor in RAS- or BRAF-mutated MM cell lines. TAS-116 monotherapy significantly inhibited growth of RAS-mutated MM cell lines and was associated with decreased expression of downstream target proteins of the RAS-RAF-MEK-ERK signaling pathway. Moreover, TAS-116 showed synergistic growth inhibitory effects with the farnesyltransferase inhibitor tipifarnib, the BRAF inhibitor dabrafenib, and the MEK inhibitor selumetinib. Importantly, treatment with these inhibitors paradoxically enhanced p-C-Raf, p-MEK, and p-ERK activity, which was abrogated by TAS-116. TAS-116 also enhanced dabrafenib-induced MM cytotoxicity associated with mitochondrial damage-induced apoptosis, even in the BRAF-mutated U266 MM cell line. This enhanced apoptosis in RAS-mutated MM triggered by combination treatment was observed even in the presence of bone marrow stromal cells. Taken together, our results provide the rationale for novel combination treatment with HSP90α/β inhibitor and RAS-RAF-MEK-ERK signaling pathway inhibitors to improve outcomes in patients with in RAS- or BRAF-mutated MM.

  18. Multiple Assembly Rules Drive the Co-occurrence of Orthopteran and Plant Species in Grasslands: Combining Network, Functional and Phylogenetic Approaches.

    PubMed

    Fournier, Bertrand; Mouly, Arnaud; Gillet, François

    2016-01-01

    Understanding the factors underlying the co-occurrence of multiple species remains a challenge in ecology. Biotic interactions, environmental filtering and neutral processes are among the main mechanisms evoked to explain species co-occurrence. However, they are most often studied separately or even considered as mutually exclusive. This likely hampers a more global understanding of species assembly. Here, we investigate the general hypothesis that the structure of co-occurrence networks results from multiple assembly rules and its potential implications for grassland ecosystems. We surveyed orthopteran and plant communities in 48 permanent grasslands of the French Jura Mountains and gathered functional and phylogenetic data for all species. We constructed a network of plant and orthopteran species co-occurrences and verified whether its structure was modular or nested. We investigated the role of all species in the structure of the network (modularity and nestedness). We also investigated the assembly rules driving the structure of the plant-orthopteran co-occurrence network by using null models on species functional traits, phylogenetic relatedness and environmental conditions. We finally compared our results to abundance-based approaches. We found that the plant-orthopteran co-occurrence network had a modular organization. Community assembly rules differed among modules for plants while interactions with plants best explained the distribution of orthopterans into modules. Few species had a disproportionately high positive contribution to this modular organization and are likely to have a key importance to modulate future changes. The impact of agricultural practices was restricted to some modules (3 out of 5) suggesting that shifts in agricultural practices might not impact the entire plant-orthopteran co-occurrence network. These findings support our hypothesis that multiple assembly rules drive the modular structure of the plant-orthopteran network. This

  19. Multiple Assembly Rules Drive the Co-occurrence of Orthopteran and Plant Species in Grasslands: Combining Network, Functional and Phylogenetic Approaches

    PubMed Central

    Fournier, Bertrand; Mouly, Arnaud; Gillet, François

    2016-01-01

    Understanding the factors underlying the co-occurrence of multiple species remains a challenge in ecology. Biotic interactions, environmental filtering and neutral processes are among the main mechanisms evoked to explain species co-occurrence. However, they are most often studied separately or even considered as mutually exclusive. This likely hampers a more global understanding of species assembly. Here, we investigate the general hypothesis that the structure of co-occurrence networks results from multiple assembly rules and its potential implications for grassland ecosystems. We surveyed orthopteran and plant communities in 48 permanent grasslands of the French Jura Mountains and gathered functional and phylogenetic data for all species. We constructed a network of plant and orthopteran species co-occurrences and verified whether its structure was modular or nested. We investigated the role of all species in the structure of the network (modularity and nestedness). We also investigated the assembly rules driving the structure of the plant-orthopteran co-occurrence network by using null models on species functional traits, phylogenetic relatedness and environmental conditions. We finally compared our results to abundance-based approaches. We found that the plant-orthopteran co-occurrence network had a modular organization. Community assembly rules differed among modules for plants while interactions with plants best explained the distribution of orthopterans into modules. Few species had a disproportionately high positive contribution to this modular organization and are likely to have a key importance to modulate future changes. The impact of agricultural practices was restricted to some modules (3 out of 5) suggesting that shifts in agricultural practices might not impact the entire plant-orthopteran co-occurrence network. These findings support our hypothesis that multiple assembly rules drive the modular structure of the plant-orthopteran network. This

  20. Formation of combined partially recessed and multiple fluorinated-dielectric layers gate structures for high threshold voltage GaN-based HEMT power devices

    NASA Astrophysics Data System (ADS)

    Huang, Huolin; Liang, Yung Chii

    2015-12-01

    The formation of partial AlGaN trench recess filled with multiple fluorinated gate dielectric layers as metal-insulator-semiconductor (MIS) gate structure for GaN-based HEMT power devices is designed, fabricated and experimentally verified. The approach realizes the device normally-off operational mode and at the same time is able to preserve the good mobility in the 2DEG channel for a maximum on-state current. Experimental measurements on the fabricated MIS-HEMT devices indicate a high gate threshold voltage (Vth) at around 5 V and a very low gate leakage current at pA/mm level. This proposed gate structure provides very promising properties for GaN-based power semiconductor devices in future power electronics switching applications.

  1. Combination of Multiple Spectral Libraries Improves the Current Search Methods Used to Identify Missing Proteins in the Chromosome-Centric Human Proteome Project.

    PubMed

    Cho, Jin-Young; Lee, Hyoung-Joo; Jeong, Seul-Ki; Kim, Kwang-Youl; Kwon, Kyung-Hoon; Yoo, Jong Shin; Omenn, Gilbert S; Baker, Mark S; Hancock, William S; Paik, Young-Ki

    2015-12-01

    Approximately 2.9 billion long base-pair human reference genome sequences are known to encode some 20 000 representative proteins. However, 3000 proteins, that is, ~15% of all proteins, have no or very weak proteomic evidence and are still missing. Missing proteins may be present in rare samples in very low abundance or be only temporarily expressed, causing problems in their detection and protein profiling. In particular, some technical limitations cause missing proteins to remain unassigned. For example, current mass spectrometry techniques have high limits and error rates for the detection of complex biological samples. An insufficient proteome coverage in a reference sequence database and spectral library also raises major issues. Thus, the development of a better strategy that results in greater sensitivity and accuracy in the search for missing proteins is necessary. To this end, we used a new strategy, which combines a reference spectral library search and a simulated spectral library search, to identify missing proteins. We built the human iRefSPL, which contains the original human reference spectral library and additional peptide sequence-spectrum match entries from other species. We also constructed the human simSPL, which contains the simulated spectra of 173 907 human tryptic peptides determined by MassAnalyzer (version 2.3.1). To prove the enhanced analytical performance of the combination of the human iRefSPL and simSPL methods for the identification of missing proteins, we attempted to reanalyze the placental tissue data set (PXD000754). The data from each experiment were analyzed using PeptideProphet, and the results were combined using iProphet. For the quality control, we applied the class-specific false-discovery rate filtering method. All of the results were filtered at a false-discovery rate of <1% at the peptide and protein levels. The quality-controlled results were then cross-checked with the neXtProt DB (2014-09-19 release). The two

  2. Behavioural mapping of a pelagic seabird: combining multiple sensors and a hidden Markov model reveals the distribution of at-sea behaviour.

    PubMed

    Dean, Ben

    2013-01-01

    The use of miniature data loggers is rapidly increasing our understanding of the movements and habitat preferences of pelagic seabirds. However, objectively interpreting behavioural information from the large volumes of highly detailed data collected by such devices can be challenging. We combined three biologging technologies—global positioning system (GPS), saltwater immersion and time–depth recorders—to build a detailed picture of the at-sea behaviour of the Manx shearwater (Puffinus puffinus) during the breeding season. We used a hidden Markov model to explore discrete states within the combined GPS and immersion data, and found that behaviour could be organized into three principal activities representing (i) sustained direct flight, (ii) sitting on the sea surface, and (iii) foraging, comprising tortuous flight interspersed with periods of immersion. The additional logger data verified that the foraging activity corresponded well to the occurrence of diving. Applying this approach to a large tracking dataset revealed that birds from two different colonies foraged in local waters that were exclusive, but overlapped in one key area: the Irish Sea Front (ISF). We show that the allocation of time to each activity differed between colonies, with birds breeding furthest from the ISF spending the greatest proportion of time engaged in direct flight and the smallest proportion of time engaged in foraging activity. This type of analysis has considerable potential for application in future biologging studies and in other taxa.

  3. Behavioural mapping of a pelagic seabird: combining multiple sensors and a hidden Markov model reveals the distribution of at-sea behaviour

    PubMed Central

    Dean, Ben; Freeman, Robin; Kirk, Holly; Leonard, Kerry; Phillips, Richard A.; Perrins, Chris M.; Guilford, Tim

    2013-01-01

    The use of miniature data loggers is rapidly increasing our understanding of the movements and habitat preferences of pelagic seabirds. However, objectively interpreting behavioural information from the large volumes of highly detailed data collected by such devices can be challenging. We combined three biologging technologies—global positioning system (GPS), saltwater immersion and time–depth recorders—to build a detailed picture of the at-sea behaviour of the Manx shearwater (Puffinus puffinus) during the breeding season. We used a hidden Markov model to explore discrete states within the combined GPS and immersion data, and found that behaviour could be organized into three principal activities representing (i) sustained direct flight, (ii) sitting on the sea surface, and (iii) foraging, comprising tortuous flight interspersed with periods of immersion. The additional logger data verified that the foraging activity corresponded well to the occurrence of diving. Applying this approach to a large tracking dataset revealed that birds from two different colonies foraged in local waters that were exclusive, but overlapped in one key area: the Irish Sea Front (ISF). We show that the allocation of time to each activity differed between colonies, with birds breeding furthest from the ISF spending the greatest proportion of time engaged in direct flight and the smallest proportion of time engaged in foraging activity. This type of analysis has considerable potential for application in future biologging studies and in other taxa. PMID:23034356

  4. Quantifying stream thermal regimes at multiple scales: Combining thermal infrared imagery and stationary stream temperature data in a novel modeling framework

    NASA Astrophysics Data System (ADS)

    Vatland, Shane J.; Gresswell, Robert E.; Poole, Geoffrey C.

    2015-01-01

    Accurately quantifying stream thermal regimes can be challenging because stream temperatures are often spatially and temporally heterogeneous. In this study, we present a novel modeling framework that combines stream temperature data sets that are continuous in either space or time. Specifically, we merged the fine spatial resolution of thermal infrared (TIR) imagery with hourly data from 10 stationary temperature loggers in a 100 km portion of the Big Hole River, MT, USA. This combination allowed us to estimate summer thermal conditions at a relatively fine spatial resolution (every ˜100 m of stream length) over a large extent of stream (˜100 km of stream) during the warmest part of the summer. Rigorous evaluation, including internal validation, external validation with spatially continuous instream temperature measurements collected from a Langrangian frame of reference, and sensitivity analyses, suggests the model was capable of accurately estimating longitudinal patterns in summer stream temperatures for this system (validation RMSEs < 1°C). Results revealed considerable spatial and temporal heterogeneity in summer stream temperatures and highlighted the value of assessing thermal regimes at relatively fine spatial and temporal scales. Preserving spatial and temporal variability and structure in abiotic stream data provides a critical foundation for understanding the dynamic, multiscale habitat needs of mobile stream organisms. Similarly, enhanced understanding of spatial and temporal variation in dynamic water quality attributes, including temporal sequence and spatial arrangement, can guide strategic placement of monitoring equipment that will subsequently capture variation in environmental conditions directly pertinent to research and management objectives.

  5. Quantifying methane emission from fugitive sources by combining tracer release and downwind measurements - a sensitivity analysis based on multiple field surveys.

    PubMed

    Mønster, Jacob G; Samuelsson, Jerker; Kjeldsen, Peter; Rella, Chris W; Scheutz, Charlotte

    2014-08-01

    Using a dual species methane/acetylene instrument based on cavity ring down spectroscopy (CRDS), the dynamic plume tracer dispersion method for quantifying the emission rate of methane was successfully tested in four measurement campaigns: (1) controlled methane and trace gas release with different trace gas configurations, (2) landfill with unknown emission source locations, (3) landfill with closely located emission sources, and (4) comparing with an Fourier transform infrared spectroscopy (FTIR) instrument using multiple trace gasses for source separation. The new real-time, high precision instrument can measure methane plumes more than 1.2 km away from small sources (about 5 kg h(-1)) in urban areas with a measurement frequency allowing plume crossing at normal driving speed. The method can be used for quantification of total methane emissions from diffuse area sources down to 1 kg per hour and can be used to quantify individual sources with the right choice of wind direction and road distance. The placement of the trace gas is important for obtaining correct quantification and uncertainty of up to 36% can be incurred when the trace gas is not co-located with the methane source. Measurements made at greater distances are less sensitive to errors in trace gas placement and model calculations showed an uncertainty of less than 5% in both urban and open-country for placing the trace gas 100 m from the source, when measurements were done more than 3 km away. Using the ratio of the integrated plume concentrations of tracer gas and methane gives the most reliable results for measurements at various distances to the source, compared to the ratio of the highest concentration in the plume, the direct concentration ratio and using a Gaussian plume model. Under suitable weather and road conditions, the CRDS system can quantify the emission from different sources located close to each other using only one kind of trace gas due to the high time resolution, while the FTIR

  6. Diagnosis and Anti-Reflux Therapy for GERD with Respiratory Symptoms: A Study Using Multichannel Intraluminal Impedance-pH Monitoring

    PubMed Central

    Zhang, Chao; Wu, Jimin; Hu, Zhiwei; Yan, Chao; Gao, Xiang; Liang, Weitao; Liu, Diangang; Li, Fei; Wang, Zhonggao

    2016-01-01

    Background/Aims Respiratory symptoms are often associated with gastroesophageal reflux disease (GERD). Although the role of multichannel intraluminal impedance–pH (MII-pH) monitoring in GERD is clear, little is known regarding the characteristics of patients with respiratory symptoms based on MII-pH monitoring and anti-reflux therapy. We evaluated a cohort of GERD patients to identify the MII-pH parameters of GERD-related respiratory symptoms and to assess the anti-reflux therapy outcomes. Methods We undertook a prospective study of patients who were referred for GERD evaluation from January 2011 to January 2012. One hundred ninety-five patients underwent MII-pH monitoring and esophageal manometry, and one hundred sixty-five patients underwent invasive anti-reflux therapy that included laparoscopic Toupet fundoplication (LTF) and the Stretta procedure. The patient characteristics and MII-pH parameters were analyzed, and the symptom scores were assessed at baseline and at 1- and 3-year follow-up evaluations. Results Of the 195 patients, 96 (49.2%) exhibited respiratory symptoms and significantly more reflux episodes (70.7±29.3) than patients without respiratory symptoms (64.7±24.4, p = 0.044) based on the MII-pH monitoring results. Moreover, the group of patients with respiratory symptoms exhibited more proximal reflux episodes (35.2±21.3) than the non-respiratory symptomatic group (28.3±17.9, p = 0.013). One hundred twenty-five patients following the Stretta procedure (n = 60, 31 with respiratory symptoms) or LTF (n = 65, 35 with respiratory symptoms) completed the designated 3-year follow-up period and were included in the final analysis. The symptom scores after anti-reflux therapy all decreased relative to the corresponding baseline values (p<0.05), and there were no significant differences in the control of respiration between the Stretta procedure and LTF (p>0.05). However, LTF significantly reduced the recurrence (re-operation) rate compared with the

  7. Towards atomic resolution in sodium titanate nanotubes using near-edge X-ray-absorption fine-structure spectromicroscopy combined with multichannel multiple-scattering calculations

    PubMed Central

    Krüger, Peter; Lagos, Maureen J; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Ewels, Chris; Umek, Polona; Guttmann, Peter

    2012-01-01

    Summary Recent advances in near-edge X-ray-absorption fine-structure spectroscopy coupled with transmission X-ray microscopy (NEXAFS–TXM) allow large-area mapping investigations of individual nano-objects with spectral resolution up to E/ΔE = 104 and spatial resolution approaching 10 nm. While the state-of-the-art spatial resolution of X-ray microscopy is limited by nanostructuring process constrains of the objective zone plate, we show here that it is possible to overcome this through close coupling with high-level theoretical modelling. Taking the example of isolated bundles of hydrothermally prepared sodium titanate nanotubes ((Na,H)TiNTs) we are able to unravel the complex nanoscale structure from the NEXAFS–TXM data using multichannel multiple-scattering calculations, to the extent of being able to associate specific spectral features in the O K-edge and Ti L-edge with oxygen atoms in distinct sites within the lattice. These can even be distinguished from the contribution of different hydroxyl groups to the electronic structure of the (Na,H)TiNTs. PMID:23213642

  8. Towards atomic resolution in sodium titanate nanotubes using near-edge X-ray-absorption fine-structure spectromicroscopy combined with multichannel multiple-scattering calculations.

    PubMed

    Bittencourt, Carla; Krüger, Peter; Lagos, Maureen J; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Ewels, Chris; Umek, Polona; Guttmann, Peter

    2012-01-01

    Recent advances in near-edge X-ray-absorption fine-structure spectroscopy coupled with transmission X-ray microscopy (NEXAFS-TXM) allow large-area mapping investigations of individual nano-objects with spectral resolution up to E/ΔE = 10(4) and spatial resolution approaching 10 nm. While the state-of-the-art spatial resolution of X-ray microscopy is limited by nanostructuring process constrains of the objective zone plate, we show here that it is possible to overcome this through close coupling with high-level theoretical modelling. Taking the example of isolated bundles of hydrothermally prepared sodium titanate nanotubes ((Na,H)TiNTs) we are able to unravel the complex nanoscale structure from the NEXAFS-TXM data using multichannel multiple-scattering calculations, to the extent of being able to associate specific spectral features in the O K-edge and Ti L-edge with oxygen atoms in distinct sites within the lattice. These can even be distinguished from the contribution of different hydroxyl groups to the electronic structure of the (Na,H)TiNTs. PMID:23213642

  9. Silencing of neurotropic flavivirus replication in the central nervous system by combining multiple microRNA target insertions in two distinct viral genome regions

    PubMed Central

    Teterina, Natalya L.; Liu, Guangping; Maximova, Olga A.; Pletnev, Alexander G.

    2014-01-01

    In recent years, microRNA-targeting has become an effective strategy for selective control of tissue-tropism and pathogenesis of both DNA and RNA viruses. Here, using a neurotropic flavivirus as a model, we demonstrate that simultaneous miRNA targeting of the viral genome in the open reading frame and 3′-noncoding regions for brain-expressed miRNAs had an additive effect and produced a more potent attenuation of the virus compared to separate targeting of those regions. Multiple miRNA co-targeting of these two distantly located regions completely abolished the virus neurotropism as no viral replication was detected in the developing brain of neonatal mice. Furthermore, no viral antigens were detected in neurons, and neuronal integrity in the brain of mice was well preserved. This miRNA co-targeting approach can be adapted for other viruses in order to minimize their replication in a cell- or tissue-type specific manner, but most importantly, to prevent virus escape from miRNA-mediated silencing. PMID:24889244

  10. Pomalidomide for Multiple Myeloma

    Cancer.gov

    A summary of results from a phase III trial that compared the combination of pomalidomide (Pomalyst®) and low-dose dexamethasone versus high-dose dexamethasone alone in patients with multiple myeloma that has progressed despite other treatments.

  11. Evaluation of multiple ancillary therapies used in combination with an antimicrobial in newly received high-risk calves treated for bovine respiratory disease.

    PubMed

    Wilson, B K; Step, D L; Maxwell, C L; Wagner, J J; Richards, C J; Krehbiel, C R

    2015-07-01

    Ancillary therapy (ANC) is commonly provided in conjunction with an antimicrobial when treating calves for suspected bovine respiratory disease (BRD) in an attempt to improve the response to a suspected BRD challenge. The first experiment evaluated the effects of 3 ANC in combination with an antimicrobial in high-risk calves treated for BRD during a 56-d receiving period. Newly received crossbred steers (n = 516; initial BW = 217 ± 20 kg) were monitored by trained personnel for clinical signs of BRD. Calves that met antimicrobial treatment criteria (n = 320) were then randomly assigned to experimental ANC treatment (80 steers/experimental ANC treatment): intravenous flunixin meglumine injection (NSAID), intranasal viral vaccination (VACC), intramuscular vitamin C injection (VITC), or no ANC (NOAC). Animal served as the experimental unit for all variables except DMI and G:F (pen served as the experimental unit for DMI and G:F). Within calves treated 3 times for BRD, those receiving NOAC had lower (P < 0.01) clinical severity scores (severity scores ranged from 0 to 4 on the basis of observed clinical signs and severity) and heavier (P = 0.01) BW than those receiving NSAID, VACC, or VITC at the time of third treatment. Between the second and third BRD treatments, calves receiving NOAC had decreased (P < 0.01) daily BW loss (−0.13 kg ADG) compared with those receiving NSAID, VACC, or VITC (−1.30, −1.90, and −1.41 kg ADG, respectively). There were no differences in rectal temperature, combined mortalities and removals, or overall performance among the experimental ANC treatments. Overall, morbidity and mortality attributed to BRD across treatments were 66.5% and 13.2%, respectively. After the receiving period, a subset of calves (n = 126) were allocated to finishing pens to evaluate the effects ANC administration on finishing performance, carcass characteristics, and lung scores at harvest. Ultrasound estimates, BW, and visual appraisal were used to target a

  12. Results of the PAS Study: A Randomized Controlled Trial Evaluating the Effectiveness of a Web-Based Multiple Tailored Smoking Cessation Program Combined With Tailored Counseling by Practice Nurses.

    PubMed

    Smit, E S; Candel, M J J M; Hoving, C; de Vries, H

    2016-09-01

    This study investigated the effects of Web-based multiple computer tailoring and counseling by a practice nurse (MTC) compared with computer tailoring without counseling (MT) and usual care (UC) on smoking cessation rates, via a randomized controlled trial with 414 Dutch adult smokers, recruited by 91 practice nurses from May 2009 to June 2010. Logistic multilevel regression analyses were conducted with 24-hour point prevalence, 7-day point prevalence, and prolonged abstinence after 6 and 12 months as dependent variables and experimental condition as the independent variable. After 6 and 12 months, 38% and 56% of respondents were followed up, respectively. At both follow-ups, no main effects of the interventions could be identified when comparing them with care as usual and with each other-neither in analyses using available data nor in analyses using a negative scenario in which respondents lost to follow-up were considered to still be smoking. A Web-based multiple computer-tailored smoking cessation program combined with a single face-to-face counseling session by a practice nurse may not be more effective than this computer-tailored program alone or than usual smoking cessation care in the general practice setting. Yet before concluding that the addition of counseling to Web-based computer tailoring cannot be successful, more research needs to be conducted to identify the optimal number of counseling sessions to be combined with the Web-based program and to how to best attune the two modalities. PMID:26934538

  13. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy

    PubMed Central

    Ricca, Alessandra; Rufo, Nicole; Ungari, Silvia; Morena, Francesco; Martino, Sabata; Kulik, Wilem; Alberizzi, Valeria; Bolino, Alessandra; Bianchi, Francesca; Del Carro, Ubaldo; Biffi, Alessandra; Gritti, Angela

    2015-01-01

    Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing dramatic extension of lifespan and global clinical–pathological rescue in a relevant GLD murine model. We show that timely and long-lasting delivery of functional GALC in affected tissues ensured by the exclusive complementary mode of action of the treatments underlies the outstanding benefit. In particular, the contribution of neural stem cell transplantation and IC GT during the early asymptomatic stage of the disease is instrumental to enhance long-term advantage upon BMT. We clarify the input of central nervous system, peripheral nervous system and periphery to the disease, and the relative contribution of treatments to the final therapeutic outcome, with important implications for treatment strategies to be tried in human patients. This study gives proof-of-concept of efficacy, tolerability and clinical relevance of the combined gene/cell therapies proposed here, which may constitute a feasible and effective therapeutic opportunity for children affected by GLD. PMID:25749991

  14. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy.

    PubMed

    Ricca, Alessandra; Rufo, Nicole; Ungari, Silvia; Morena, Francesco; Martino, Sabata; Kulik, Wilem; Alberizzi, Valeria; Bolino, Alessandra; Bianchi, Francesca; Del Carro, Ubaldo; Biffi, Alessandra; Gritti, Angela

    2015-06-15

    Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing dramatic extension of lifespan and global clinical-pathological rescue in a relevant GLD murine model. We show that timely and long-lasting delivery of functional GALC in affected tissues ensured by the exclusive complementary mode of action of the treatments underlies the outstanding benefit. In particular, the contribution of neural stem cell transplantation and IC GT during the early asymptomatic stage of the disease is instrumental to enhance long-term advantage upon BMT. We clarify the input of central nervous system, peripheral nervous system and periphery to the disease, and the relative contribution of treatments to the final therapeutic outcome, with important implications for treatment strategies to be tried in human patients. This study gives proof-of-concept of efficacy, tolerability and clinical relevance of the combined gene/cell therapies proposed here, which may constitute a feasible and effective therapeutic opportunity for children affected by GLD.

  15. [Multiple myeloma].

    PubMed

    Abe, Masahiro; Miki, Hirokazu; Nakamura, Shingen

    2016-03-01

    Owing to the positive clinical benefits obtained with new agents, complete remission (CR) can be used as a surrogate for overall survival, and should be achieved. Although multiple myeloma is a heterogeneous disease in terms of myeloma cell- and patient-related risk factors, patients should receive the most effective combination therapy based on proteasome inhibitors and/or immunomodulatory drugs (IMiDs) as backbone medication irrespective of the risks encountered in the setting of induction therapy ("one-size-fits-all" therapy), followed by consolidation/maintenance therapy to achieve CR with the ultimate goal of extended survival. Myeloma-defining biomarkers have been established to identify high-risk smoldering myeloma requiring treatment. The development of salvage treatments yielding better outcomes for relapsed/refractory myeloma is urgently needed. Upcoming novel molecular targeting agents with different modes of action and immunotherapeutic agents will be integrated into myeloma treatment regimens with a great therapeutic impact, and further evolution of the treatment paradigm for multiple myeloma is eagerly anticipated. PMID:27076236

  16. Nitrate source identification in groundwater of multiple land-use areas by combining isotopes and multivariate statistical analysis: A case study of Asopos basin (Central Greece).

    PubMed

    Matiatos, Ioannis

    2016-01-15

    Nitrate (NO3) is one of the most common contaminants in aquatic environments and groundwater. Nitrate concentrations and environmental isotope data (δ(15)N-NO3 and δ(18)O-NO3) from groundwater of Asopos basin, which has different land-use types, i.e., a large number of industries (e.g., textile, metal processing, food, fertilizers, paint), urban and agricultural areas and livestock breeding facilities, were analyzed to identify the nitrate sources of water contamination and N-biogeochemical transformations. A Bayesian isotope mixing model (SIAR) and multivariate statistical analysis of hydrochemical data were used to estimate the proportional contribution of different NO3 sources and to identify the dominant factors controlling the nitrate content of the groundwater in the region. The comparison of SIAR and Principal Component Analysis showed that wastes originating from urban and industrial zones of the basin are mainly responsible for nitrate contamination of groundwater in these areas. Agricultural fertilizers and manure likely contribute to groundwater contamination away from urban fabric and industrial land-use areas. Soil contribution to nitrate contamination due to organic matter is higher in the south-western part of the area far from the industries and the urban settlements. The present study aims to highlight the use of environmental isotopes combined with multivariate statistical analysis in locating sources of nitrate contamination in groundwater leading to a more effective planning of environmental measures and remediation strategies in river basins and water bodies as defined by the European Water Frame Directive (Directive 2000/60/EC). PMID:26437351

  17. Nitrate source identification in groundwater of multiple land-use areas by combining isotopes and multivariate statistical analysis: A case study of Asopos basin (Central Greece).

    PubMed

    Matiatos, Ioannis

    2016-01-15

    Nitrate (NO3) is one of the most common contaminants in aquatic environments and groundwater. Nitrate concentrations and environmental isotope data (δ(15)N-NO3 and δ(18)O-NO3) from groundwater of Asopos basin, which has different land-use types, i.e., a large number of industries (e.g., textile, metal processing, food, fertilizers, paint), urban and agricultural areas and livestock breeding facilities, were analyzed to identify the nitrate sources of water contamination and N-biogeochemical transformations. A Bayesian isotope mixing model (SIAR) and multivariate statistical analysis of hydrochemical data were used to estimate the proportional contribution of different NO3 sources and to identify the dominant factors controlling the nitrate content of the groundwater in the region. The comparison of SIAR and Principal Component Analysis showed that wastes originating from urban and industrial zones of the basin are mainly responsible for nitrate contamination of groundwater in these areas. Agricultural fertilizers and manure likely contribute to groundwater contamination away from urban fabric and industrial land-use areas. Soil contribution to nitrate contamination due to organic matter is higher in the south-western part of the area far from the industries and the urban settlements. The present study aims to highlight the use of environmental isotopes combined with multivariate statistical analysis in locating sources of nitrate contamination in groundwater leading to a more effective planning of environmental measures and remediation strategies in river basins and water bodies as defined by the European Water Frame Directive (Directive 2000/60/EC).

  18. Changes in the fluorescence composition of multiple DOM sources over pH gradients assessed by combining parallel factor analysis and self-organizing maps

    NASA Astrophysics Data System (ADS)

    Cuss, C. W.; Shi, Y. X.; McConnell, S. M.; Guéguen, C.

    2014-09-01

    Dissolved organic matter is a ubiquitous constituent of natural waters that plays key roles in several important processes. The fluorescence properties of DOM have been linked to its functionality, but these properties may vary with pH. In this study Kohonen's self-organizing maps (SOMs) were applied to excitation-emission matrices (EEMs) of fresh dissolved organic matter (DOM) from three sources: senescent sugar-maple leaves and white spruce needles, and humified white spruce needles, over a pH range of ~4.5 - 12.5. SOMs were applied to raw EEMs, EEMs reduced in dimensionality by pre-processing using parallel factor analysis (PARAFAC), and PARAFAC loading proportions normalized to values at initial pH. Some separation of EEMs into source-based clusters was achieved in the SOM of raw EEMs, but commingling was apparent and evidence of changes over pH gradients was overshadowed. SOMs of PARAFAC component proportions demonstrated clear source-based clustering, and pH-based gradients were visible for DOM from senescent and humified spruce needles. Changes in optical properties were obvious over pH gradients in the SOM of components normalized to starting condition. Component proportions decreased to values as low as 5% of the initial values for microbial humic-like peak M and increased to as high as 278% for a humic-like component. Tyrosine-like fluorescence increased to 112% of initial over increasing pH in humified spruce leachates but decreased to as low as 45% in the other leachates. The combination of PARAFAC and SOM drastically enhanced visualization and interpretability of pH-induced changes in DOM compared to either method alone.

  19. Multiple-pressure-source model for ground inflation during the period of high explosivity at Sakurajima volcano, Japan - Combination analysis of continuous GNSS, tilt and strain data -

    NASA Astrophysics Data System (ADS)

    Hotta, Kohei; Iguchi, Masato; Ohkura, Takahiro; Yamamoto, Keigo

    2016-01-01

    We herein propose a three-pressure-source model for ground inflation with highly eruptive activity at the Showa crater of Sakurajima volcano, Japan. We applied a model of stacked spherical sources to continuous combined geodetic data from a global navigation satellite system, tilt and strainmeters. The data were recorded during ground inflation throughout an eruptive episode that began in October 2011 and ended in March 2012. Using a genetic algorithm, we obtained the locations and volumes of three sources. A pressure source analysis of ground inflation during the period from October 2011 to March 2012 revealed inflation sources to be located at a depth of 9.6 km beneath Aira caldera (A-source) and 3.3 km beneath Kita-dake (K-source), and a shallow deflation source is located at a depth of 0.7 km beneath Minami-dake (M-source). The A-source corresponds to the main magma reservoir at a depth of 10 km beneath the Aira caldera inferred by previous geophysical studies. The K-source is a-reservoir of Sakurajima volcano, where magma intrudes from the main magma reservoir beneath the Aira caldera during the first stage of eruptive activity. The M-source is the uppermost part of a conduit from the K-source to the summit and the Showa crater. Magma injection into the A-source started in mid-November 2011, instantly triggering the migration of increased volumes of magma from the A-source to the K-source. Approximately one month later, in mid-December 2011, an increased volume of magma started migrating from the K-source to the M-source and finally erupted at the surface. The accumulation rate for the A-source is comparable to the magma supply rate for the past 100 years (0.8 to 1.6 × 107 m3). The three-pressure-source model was applied to inflation events before the 2011 event in order to reconstruct the magma migration process. Applying our source model to earlier activity phases, we found that injected magma from the A-source remained at the K-source and a small amount of

  20. Treatment with the HIV protease inhibitor nelfinavir triggers the unfolded protein response and may overcome proteasome inhibitor resistance of multiple myeloma in combination with bortezomib: a phase I trial (SAKK 65/08)

    PubMed Central

    Driessen, Christoph; Kraus, Marianne; Joerger, Markus; Rosing, Hilde; Bader, Jürgen; Hitz, Felicitas; Berset, Catherine; Xyrafas, Alexandros; Hawle, Hanne; Berthod, Gregoire; Overkleeft, Hermann S.; Sessa, Christiana; Huitema, Alwin; Pabst, Thomas; von Moos, Roger; Hess, Dagmar; Mey, Ulrich J.M.

    2016-01-01

    Downregulation of the unfolded protein response mediates proteasome inhibitor resistance in multiple myeloma. The Human Immunodeficieny Virus protease inhibitor nelfinavir activates the unfolded protein response in vitro. We determined dose-limiting toxicity and recommended dose for phase II of nelfinavir in combination with the proteasome inhibitor bortezomib. Twelve patients with advanced hematologic malignancies were treated with nelfinavir (2500–5000 mg/day p.o., days 1–14, 3+3 dose escalation) and bortezomib (1.3 mg/m2, days 1, 4, 8, 11; 21-day cycles). A run in phase with nelfinavir monotherapy allowed pharmakokinetic/pharmakodynamic assessment of nelfinavir in the presence or absence of concomittant bortezomib. End points included dose-limiting toxicity, activation of the unfolded protein response, proteasome activity, toxicity and response to trial treatment. Nelfinavir 2×2500 mg was the recommended phase II dose identified. Nelfinavir alone significantly up-regulated expression of proteins related to the unfolded protein response in peripheral blood mononuclear cells and inhibited proteasome activity. Of 10 evaluable patients in the dose escalation cohort, 3 achieved a partial response, 4 stable disease for 2 cycles or more, while 3 had progressive disease as best response. In an exploratory extension cohort with 6 relapsed, bortezomib-refractory, lenalidomide-resistant myeloma patients treated at the recommended phase II dose, 3 reached a partial response, 2 a minor response, and one progressive disease. The combination of nelfinavir with bortezomib is safe and shows promising activity in advanced, bortezomib-refractory multiple myeloma. Induction of the unfolded protein response by nelfinavir may overcome the biological features of proteasome inhibitor resistance. PMID:26659919

  1. Layout decomposition and synthesis for a modular technology to solve the edge-placement challenges by combining selective etching, direct stitching, and alternating-material self-aligned multiple patterning processes

    NASA Astrophysics Data System (ADS)

    Liu, Hongyi; Han, Ting; Zhou, Jun; Chen, Yijian

    2016-03-01

    To overcome the prohibitive barriers of edge-placement errors (EPE) in the cut/block/via step of complementary lithography, we propose a modular patterning approach by combining layout stitching, selective etching, and alternating-material self-aligned multiple patterning (altSAMP) processes. In this patterning approach, altSAMP is used to create line arrays with two materials alternatively which allow a highly selective etching process to remove one material without attacking the other, therefore more significant EPE effect can be tolerated in line-cutting step. With no need of connecting vias, the stitching process can form 2-D features by directly stitching two components of patterns together to create 2-D design freedom as well as multiple-CD/pitch capability. By adopting this novel approach, we can potentially achieve higher processing yield and more 2-D design freedom for continuous IC scaling down to 5 nm. We developed layout decomposition and synthesis algorithms for critical layers, and the fin/gate/metal layer from NSCU open cell library is used to test the proposed algorithms.

  2. Global Profiling and Novel Structure Discovery Using Multiple Neutral Loss/Precursor Ion Scanning Combined with Substructure Recognition and Statistical Analysis (MNPSS): Characterization of Terpene-Conjugated Curcuminoids in Curcuma longa as a Case Study.

    PubMed

    Qiao, Xue; Lin, Xiong-hao; Ji, Shuai; Zhang, Zheng-xiang; Bo, Tao; Guo, De-an; Ye, Min

    2016-01-01

    To fully understand the chemical diversity of an herbal medicine is challenging. In this work, we describe a new approach to globally profile and discover novel compounds from an herbal extract using multiple neutral loss/precursor ion scanning combined with substructure recognition and statistical analysis. Turmeric (the rhizomes of Curcuma longa L.) was used as an example. This approach consists of three steps: (i) multiple neutral loss/precursor ion scanning to obtain substructure information; (ii) targeted identification of new compounds by extracted ion current and substructure recognition; and (iii) untargeted identification using total ion current and multivariate statistical analysis to discover novel structures. Using this approach, 846 terpecurcumins (terpene-conjugated curcuminoids) were discovered from turmeric, including a number of potentially novel compounds. Furthermore, two unprecedented compounds (terpecurcumins X and Y) were purified, and their structures were identified by NMR spectroscopy. This study extended the application of mass spectrometry to global profiling of natural products in herbal medicines and could help chemists to rapidly discover novel compounds from a complex matrix.

  3. Physiological, biochemical, and genome-wide transcriptional analysis reveals that elevated CO2 mitigates the impact of combined heat wave and drought stress in Arabidopsis thaliana at multiple organizational levels.

    PubMed

    Zinta, Gaurav; AbdElgawad, Hamada; Domagalska, Malgorzata A; Vergauwen, Lucia; Knapen, Dries; Nijs, Ivan; Janssens, Ivan A; Beemster, Gerrit T S; Asard, Han

    2014-12-01

    Climate changes increasingly threaten plant growth and productivity. Such changes are complex and involve multiple environmental factors, including rising CO2 levels and climate extreme events. As the molecular and physiological mechanisms underlying plant responses to realistic future climate extreme conditions are still poorly understood, a multiple organizational level analysis (i.e. eco-physiological, biochemical, and transcriptional) was performed, using Arabidopsis exposed to incremental heat wave and water deficit under ambient and elevated CO2 . The climate extreme resulted in biomass reduction, photosynthesis inhibition, and considerable increases in stress parameters. Photosynthesis was a major target as demonstrated at the physiological and transcriptional levels. In contrast, the climate extreme treatment induced a protective effect on oxidative membrane damage, most likely as a result of strongly increased lipophilic antioxidants and membrane-protecting enzymes. Elevated CO2 significantly mitigated the negative impact of a combined heat and drought, as apparent in biomass reduction, photosynthesis inhibition, chlorophyll fluorescence decline, H2 O2 production, and protein oxidation. Analysis of enzymatic and molecular antioxidants revealed that the stress-mitigating CO2 effect operates through up-regulation of antioxidant defense metabolism, as well as by reduced photorespiration resulting in lowered oxidative pressure. Therefore, exposure to future climate extreme episodes will negatively impact plant growth and production, but elevated CO2 is likely to mitigate this effect.

  4. COMBINES AND COMBINING.

    ERIC Educational Resources Information Center

    RIDENOUR, HARLAN E.

    THROUGH THE USE OF THIS MANUAL, VOCATIONAL AGRICULTURE STUDENTS WITH OCCUPATIONAL INTEREST IN GRAIN FARMING AND CUSTOM COMBINE OPERATION MAY GAIN KNOWLEDGE ABOUT THE BASIC DESIGN AND OPERATION OF COMBINES. DEVELOPMENT BY A STATE CURRICULUM MATERIALS DIRECTOR INCLUDED CONSULTATION WITH ENGINEERS, TRIAL, AND REVISION. OBJECTIVES ARE STATED IN TERMS…

  5. Multiple sclerosis.

    PubMed

    Filippi, Massimo; Preziosa, Paolo; Rocca, Maria A

    2016-01-01

    Due to its sensitivity to the different multiple sclerosis (MS)-related abnormalities, magnetic resonance imaging (MRI) has become an established tool to diagnose MS and to monitor its evolution. MRI has been included in the diagnostic workup of patients with clinically isolated syndromes suggestive of MS, and ad hoc criteria have been proposed and are regularly updated. In patients with definite MS, the ability of conventional MRI techniques to explain patients' clinical status and progression of disability is still suboptimal. Several advanced MRI-based technologies have been applied to estimate overall MS burden in the different phases of the disease. Their use has allowed the heterogeneity of MS pathology in focal lesions, normal-appearing white matter and gray matter to be graded in vivo. Recently, additional features of MS pathology, including macrophage infiltration and abnormal iron deposition, have become quantifiable. All of this, combined with functional imaging techniques, is improving our understanding of the mechanisms associated with MS evolution. In the near future, the use of ultrahigh-field systems is likely to provide additional insight into disease pathophysiology. However, the utility of advanced MRI techniques in clinical trial monitoring and in assessing individual patients' response to treatment still needs to be assessed. PMID:27432676

  6. Multiple Pregnancy

    MedlinePlus

    ... is called multiple pregnancy . If more than one egg is released during the menstrual cycle and each ... fraternal twins (or more). When a single fertilized egg splits, it results in multiple identical embryos. This ...

  7. Multiple myeloma

    MedlinePlus

    Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... Multiple myeloma most commonly causes: Low red blood cell count ( anemia ), which can lead to fatigue and ...

  8. Multiple Sclerosis

    MedlinePlus

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the ... attacks healthy cells in your body by mistake. Multiple sclerosis affects women more than men. It often begins ...

  9. Finger Multiplication

    ERIC Educational Resources Information Center

    Simanihuruk, Mudin

    2011-01-01

    Multiplication facts are difficult to teach. Therefore many researchers have put a great deal of effort into finding multiplication strategies. Sherin and Fuson (2005) provided a good survey paper on the multiplication strategies research area. Kolpas (2002), Rendtorff (1908), Dabell (2001), Musser (1966) and Markarian (2009) proposed the finger…

  10. Multiple Sclerosis

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Multiple Sclerosis Information Page Condensed from Multiple Sclerosis: Hope Through ... en Español Additional resources from MedlinePlus What is Multiple Sclerosis? An unpredictable disease of the central nervous system, ...

  11. Multiplicity Counting

    SciTech Connect

    Geist, William H.

    2015-12-01

    This set of slides begins by giving background and a review of neutron counting; three attributes of a verification item are discussed: 240Pueff mass; α, the ratio of (α,n) neutrons to spontaneous fission neutrons; and leakage multiplication. It then takes up neutron detector systems – theory & concepts (coincidence counting, moderation, die-away time); detector systems – some important details (deadtime, corrections); introduction to multiplicity counting; multiplicity electronics and example distributions; singles, doubles, and triples from measured multiplicity distributions; and the point model: multiplicity mathematics.

  12. Interfacial phases in epitaxial growth of Y{sub 2}O{sub 3} on MgO studied via combining electron energy-loss spectroscopy and real-space self-consistent full multiple scattering calculations

    SciTech Connect

    Pailloux, F.; Jublot, M.; Gaboriaud, R.J.; Jaouen, M.; Paumier, F.; Imhoff, D.

    2005-09-15

    Electron energy loss spectroscopy (EELS), high resolution transmission electron microscopy (HRTEM), and electron diffraction were used to investigate Y{sub 2}O{sub 3} thin films epitaxially grown on (001) MgO substrate. In the vicinity of the film/substrate interface, HRTEM experiments evidenced the presence of grains with various crystallographic structures most of them crystallizing in the well-known Ia3 cubic phase. Some other grains, nanometric in size, and only observed in the vicinity of the film/substrate interface, have a different and unknown crystallographic structure. EELS spectra have been acquired close to the Y{sub 2}O{sub 3}/MgO interface, to get a better knowledge of the phases nucleated close to the substrate surface. Spectra exhibiting different fine structures have been recorded and compared to multiple scattering calculations. The Ia3 phase has been detected as constituting the main component of the Y{sub 2}O{sub 3} thin film in agreement with previous observations. It is found that calculations performed in a real space self-consistent full multiple scattering scheme (SC-FMS) and experiments are in pretty good agreement even for small cluster sizes. The second family of spectra has also been compared to calculations performed for monoclinic C2/m yttrium oxide, with a little success. Another approach considering a local oxygen neighboring close to a distorted rock-salt-like structure led to a good match between experimental and calculated spectra. Our results emphasize how powerful is the combination of spectroscopic measurements at nanometer scale, as feasible with EELS and modern microscopes, with ab initio calculations for structure determination at such small scale lengths.

  13. Solid-phase based on-chip DNA purification through a valve-free stepwise injection of multiple reagents employing centrifugal force combined with a hydrophobic capillary barrier pressure.

    PubMed

    Zhang, Hainan; Tran, Hong Hanh; Chung, Bong Hyun; Lee, Nae Yoon

    2013-03-21

    In this paper, we demonstrate a simple technique for sequentially introducing multiple sample liquids into microchannels driven by centrifugal force combined with a hydrophobic barrier pressure and apply the technique for performing solid-phase based on-chip DNA purification. Three microchannels with varying widths, all equipped with independent sample reservoirs at the inlets, were fabricated on a hydrophobic elastomer, poly(dimethylsiloxane) (PDMS). First, glass beads were packed inside the reaction chamber, and a whole cell containing the DNA extract was introduced into the widest channel by applying centrifugal force for physical adsorption of the DNA onto the glass beads. Next, washing and elution solutions were sequentially introduced into the intermediate and narrowest microchannels, respectively, by gradually increasing the amount of centrifugal force. Through a precise manipulation of the centrifugal force, the DNA adsorbed onto the glass beads was successfully washed and eluted in a continuous manner without the need to introduce each solution manually. A stepwise injection of liquids was successfully demonstrated using multiple ink solutions, the results of which corresponded well with the theoretical analyses. As a practical application, the D1S80 locus of human genomic DNA, which is widely used for forensic purposes, was successfully purified using the microdevice introduced in this study, as demonstrated through successful target amplification. This will pave the way for the construction of a control-free valve system for realizing on-chip DNA purification, which is one of the most labor-intensive and hard-to-miniaturize components, on a greatly simplified and miniaturized platform employing hydrophobic PDMS.

  14. Lipopolysaccharide-Induced CXCL10 mRNA Level and Six Stimulant-mRNA Combinations in Whole Blood: Novel Biomarkers for Bortezomib Responses Obtained from a Prospective Multicenter Trial for Patients with Multiple Myeloma.

    PubMed

    Watanabe, Takashi; Mitsuhashi, Masato; Sagawa, Morihiko; Ri, Masaki; Suzuki, Kenshi; Abe, Masahiro; Ohmachi, Ken; Nakagawa, Yasunori; Nakamura, Shingen; Chosa, Mizuki; Iida, Shinsuke; Kizaki, Masahiro

    2015-01-01

    To identify predictive biomarkers for clinical responses to bortezomib treatment, 0.06 mL of each whole blood without any cell separation procedures was stimulated ex vivo using five agents, and eight mRNAs were quantified. In six centers, heparinized peripheral blood was prospectively obtained from 80 previously treated or untreated, symptomatic multiple myeloma (MM) patients with measurable levels of M-proteins. The blood sample was procured prior to treatment as well as 2-3 days and 1-3 weeks after the first dose of bortezomib, which was intravenously administered biweekly or weekly, during the first cycle. Six stimulant-mRNA combinations; that is, lipopolysaccharide (LPS)-granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS-CXCL chemokine 10 (CXCL10), LPS-CCL chemokine 4 (CCL4), phytohemagglutinin-CCL4, zymosan A (ZA)-GMCSF and ZA-CCL4 showed significantly higher induction in the complete and very good partial response group than in the stable and progressive disease group, as determined by both parametric (t-test) and non-parametric (unpaired Mann-Whitney test) tests. Moreover, LPS-induced CXCL10 mRNA expression was significantly suppressed 2-3 days after the first dose of bortezomib in all patients, as determined by both parametric (t-test) and non-parametric (paired Wilcoxon test) tests, whereas the complete and very good partial response group showed sustained suppression 1-3 weeks after the first dose. Thus, pretreatment LPS-CXCL10 mRNA and/or the six combinations may serve as potential biomarkers for the response to bortezomib treatment in MM patients.

  15. Full multiple scattering analysis of XANES at the Cd L3 and O K edges in CdO films combined with a soft-x-ray emission investigation

    SciTech Connect

    Demchenko, I. N.; Denlinger, J. D.; Chernyshova, M.; Yu, K. M.; Speaks, D. T.; Olalde-Velasco, P.; Hemmers, O.; Walukiewicz, W.; Derkachova, A.; Lawniczak-Jablonska, K.

    2010-07-05

    X-ray absorption near edge structure (XANES) at the cadmium L3 and oxygen K edges for CdO thin films grown by pulsed laser deposition method, is interpreted within the real-space multiple scattering formalism, FEFF code. The features in the experimental spectra are well reproduced by calculations for a cluster of about six and ten coordination shells around the absorber for L3 edge of Cd and K edge of O, respectively. The calculated projected electronic density of states is found to be in good agreement with unoccupied electronic states in experimental data and allows to conclude that the orbital character of the lowest energy of the conductive band is Cd-5s-O-2p. The charge transfer has been quantified and not purely ionic bonding has been found. Combined XANES and resonant inelastic x-ray scattering measurements allow us to determine the direct and indirect band gap of investigated CdO films to be {approx}2.4-eV and {approx}0.9-eV, respectively.

  16. Representing Multiplication

    ERIC Educational Resources Information Center

    Harries, Tony; Barmby, Patrick

    2008-01-01

    In this study, the authors wish to explore the use of visual representations in facilitating the understanding of multiplication. In doing so, they examine the different aspects of multiplication that they can access through different representations. In addition, they draw on a study that they have been carrying out looking at pupils' actual use…

  17. Y-configured metallic stent combined with 125I seed strands cavity brachytherapy for a patient with type IV Klatskin tumor

    PubMed Central

    Dechao, Jiao; Yanli, Wang; Zhen, Li

    2016-01-01

    We report a case in an inoperable patient with type IV Klatskin tumor treated by the use of a novel, two piece, Y-configured self-expandable metallic stent (SEMS) combined with two 125I seed strands via bilateral approach. The placement of the Y-shaped SEMS was successful and resulted in adequate biliary drainage. After 2 months of intraluminal brachytherapy (ILBT), both 125I seed strands and temporary drainage catheter were removed after patency of the expanded stents was confirmed by the cholangiogram. This technique was feasible and could be considered for the treatment of patients with Bismuth type IV Klatskin tumors.

  18. Y-configured metallic stent combined with 125I seed strands cavity brachytherapy for a patient with type IV Klatskin tumor

    PubMed Central

    Dechao, Jiao; Yanli, Wang; Zhen, Li

    2016-01-01

    We report a case in an inoperable patient with type IV Klatskin tumor treated by the use of a novel, two piece, Y-configured self-expandable metallic stent (SEMS) combined with two 125I seed strands via bilateral approach. The placement of the Y-shaped SEMS was successful and resulted in adequate biliary drainage. After 2 months of intraluminal brachytherapy (ILBT), both 125I seed strands and temporary drainage catheter were removed after patency of the expanded stents was confirmed by the cholangiogram. This technique was feasible and could be considered for the treatment of patients with Bismuth type IV Klatskin tumors. PMID:27648091

  19. Multiple homicides.

    PubMed

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  20. Bone formation following lenalidomide-dexamethasone combination therapy in cases of multiple myeloma refractory to high-dose chemotherapy with bortezomib and autologous peripheral blood stem cell transplantation: report of a case and review of the literature

    PubMed Central

    Sekiguchi, Yasunobu; Ichikawa, Kunimoto; Wakabayashi, Mutsumi; Sugimoto, Keiji; Tomita, Shigeki; Izumi, Hiroshi; Nakamura, Noriko; Sawada, Tomohiro; Ohta, Yasunori; Komatsu, Norio; Noguchi, Masaaki

    2015-01-01

    A 41-year-old man presented with the chief complaint of right hip pain that had persisted for 6 months. F18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging showed FDG accumulation in the right pubic bone. A bone biopsy specimen from the site revealed findings suggestive of a plasma cell tumor. Bone marrow examination and serum and urine immunofixation tests showed no abnormalities. Based on these findings, the patient was diagnosed as having non-secretory multiple myeloma. FDG accumulation in the right pubic bone diminished following four cycles of weekly bortezomib and concomitant dexamethasone therapy. Tandem autologous peripheral blood stem cell transplantation was performed, followed by monthly bortezomib/dexamethasone maintenance therapy. A further FDG-PET/CT scan 9 months after the start of therapy indicated that FDG accumulation in the right pubic bone had worsened. Consequently, the therapy was switched to twice-weekly bortezomib/dexamethasone as remission re-induction therapy. New FDG uptake in the right hip bone was noted after six cycles of the therapy, and plain X-ray examination revealed osteolytic changes. The patient was then administered eight cycles of combined lenalidomide-dexamethasone therapy, which resulted in a marked decrease of the FDG accumulation in the right pubic bone and disappearance of uptake in the right hip bone. There was radiographic evidence of bone formation at these sites. This is only the second reported case in which treatment with the immunomodulatory drug lenalidomide and concomitant dexamethasone has been found to induce bone formation. PMID:26464727

  1. Associations among Inflammatory Biomarkers in the Circulating, Plasmatic, Salivary and Intraluminal Anatomical Compartments in Apparently Healthy Preschool Children from the Western Highlands of Guatemala

    PubMed Central

    Soto-Méndez, María José; Romero-Abal, María Eugenia; Aguilera, Concepción María; Rico, María Cruz; Solomons, Noel W.; Schümann, Klaus; Gil, Angel

    2015-01-01

    Background Undernutrition and inflammation are related in many ways; for instance, non-hygienic environments are associated with both poor growth and immunostimulation in children. Objective To describe any existing interaction among different inflammation biomarkers measured in the distinct anatomical compartments of whole blood, feces, plasma and saliva. Methods In this descriptive, cross-sectional study, samples of whole blood, feces, plasma and saliva were collected on the 8th and last week of observation among 87 attendees (42 girls and 45 boys) of 3 daycare centers offering a common 40-day rotating menu in Guatemala’s Western Highlands. Analyses included white blood cell count (WBC), fecal calprotectin, and plasmatic and salivary cytokines including IL-1B, IL-6, IL-8, IL-10 and TNF-α. Associations were assessed using Spearman rank-order and goodness-of-fit correlations, as indicated, followed by backwards-elimination multiple regression analyses to determine predictor variables for IL-10 in both anatomical compartments. Results Of a total of 66 cross-tabulations in the Spearman hemi-matrix, 22 (33%) were significantly associated. All 10 paired associations among the salivary cytokines had a significant r value, whereas 7 of 10 possible associations among plasma cytokines were significant. Associations across anatomical compartments, however, were rarely significant. IL-10 in both biological fluids were higher than corresponding reference values. When a multiple regression model was run in order to determine independent predictors for IL-10 in each anatomical compartment separately, IL-6, IL-8 and TNF-α emerged as predictors in plasma (r2 = 0.514) and IL-1B, IL-8 and TNF-α remained as independent predictors in saliva (r2 = 0.762). Significant cross-interactions were seen with WBC, but not with fecal calprotectin. Conclusion Interactions ranged from robust within the same anatomical compartment to limited to nil across distinct anatomical compartments. The

  2. Breast-feeding multiples.

    PubMed

    Flidel-Rimon, O; Shinwell, E S

    2002-06-01

    Human breast milk is the best nutrition for human infants. Its advantages over the milk of other species, such as cows, include both a reduced risk for infections, allergies and chronic diseases, together with the full nutritional requirements for growth and development. Breast-feeding is as important for multiples as for singletons. Despite the advantages, multiples receive less breast-feeding than singletons. Common reasons for not breast-feeding multiples include the fear of not fulfilling the infants' needs and the difficulty of coping with the demands on the mother's time. In addition, many multiples are delivered prematurely and by Caesarean section. Maternal pain and discomfort together with anxiety over the infants' condition are not conducive to successful breast-feeding. During lactation, the mother needs to add calories to her daily diet. It has been recommended to add approximately 500-600 kcal/day for each infant. Thus, between eating, nursing and sleeping, life is very busy for the mother of multiples. However, there is evidence that, with appropriate nutrition, one mother can nourish more than one infant. Also, simultaneous breast-feeding can save much time. Combined efforts of parents, close family, friends and the medical team can help to make either full or partial breast-feeding of multiples possible. However, when breast-feeding is not possible, health care workers need to carefully avoid judgmental approaches that may induce feelings of guilt.

  3. Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  4. Multiple stage multiple filter hydrate store

    DOEpatents

    Bjorkman, Jr., Harry K.

    1983-05-31

    An improved hydrate store for a metal halogen battery system is disclosed which employs a multiple stage, multiple filter means or separating the halogen hydrate from the liquid used in forming the hydrate. The filter means is constructed in the form of three separate sections which combine to substantially cover the interior surface of the store container. Exit conduit means is provided in association with the filter means for transmitting liquid passing through the filter means to a hydrate former subsystem. The hydrate former subsystem combines the halogen gas generated during the charging of the battery system with the liquid to form the hydrate in association with the store. Relief valve means is interposed in the exit conduit means for controlling the operation of the separate sections of the filter means, such that the liquid flow through the exit conduit means from each of the separate sections is controlled in a predetermined sequence. The three separate sections of the filter means operate in three discrete stages to provide a substantially uniform liquid flow to the hydrate former subsystem during the charging of the battery system. The separation of the liquid from the hydrate causes an increase in the density of the hydrate by concentrating the hydrate along the filter means.

  5. Multiple stage multiple filter hydrate store

    DOEpatents

    Bjorkman, H.K. Jr.

    1983-05-31

    An improved hydrate store for a metal halogen battery system is disclosed which employs a multiple stage, multiple filter means for separating the halogen hydrate from the liquid used in forming the hydrate. The filter means is constructed in the form of three separate sections which combine to substantially cover the interior surface of the store container. Exit conduit means is provided in association with the filter means for transmitting liquid passing through the filter means to a hydrate former subsystem. The hydrate former subsystem combines the halogen gas generated during the charging of the battery system with the liquid to form the hydrate in association with the store. Relief valve means is interposed in the exit conduit means for controlling the operation of the separate sections of the filter means, such that the liquid flow through the exit conduit means from each of the separate sections is controlled in a predetermined sequence. The three separate sections of the filter means operate in three discrete stages to provide a substantially uniform liquid flow to the hydrate former subsystem during the charging of the battery system. The separation of the liquid from the hydrate causes an increase in the density of the hydrate by concentrating the hydrate along the filter means. 7 figs.

  6. Multiple Sclerosis

    PubMed Central

    2013-01-01

    Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system. Common manifestations include paresthesias, diplopia, loss of vision, numbness or weakness of the limbs, bowel or bladder dysfunction, spasticity, ataxia, fatigue, and mental changes. Four main patterns of MS are recognized: relapsing remitting, primary progressive, secondary progressive, and progressive relapsing. The cause of MS is unknown, although it appears to be an autoimmune disease. Much of what is known about MS has been learned from an animal model of the disease, experimental allergic encephalomyelitis. PMID:24381825

  7. Multiple Sclerosis.

    PubMed

    Schiess, Nicoline; Calabresi, Peter A

    2016-08-01

    It is estimated that there are 300,000 people with multiple sclerosis (MS) in the United States and 2.3 million worldwide. Each MS attack can affect function in cognitive, emotional, motoric, sensory, or visual domains. Patients are often struck in the prime of their lives as they attempt to move forward with career, and family. Since the previous 2010 Seminars in Neurology Pearls and Pitfalls issue, the world of MS has drastically changed and advanced. Here the authors address the ever-changing MS world in both treatment options and diagnostics, covering easily missed differential diagnoses, newly available immunomodulatory therapy, and the challenges of safely treating patients. PMID:27643903

  8. Multiple myeloma

    PubMed Central

    Rajkumar, S. Vincent

    2008-01-01

    Multiple myeloma is a clonal plasma cell malignancy that accounts for slightly more than 10% of all hematologic cancers. In this paper, we present a historically focused review of the disease, from the description of the first case in 1844 to the present. The evolution of drug therapy and stem-cell transplantation for the treatment of myeloma, as well as the development of new agents, is discussed. We also provide an update on current concepts of diagnosis and therapy, with an emphasis on how treatments have emerged from a historical perspective after certain important discoveries and the results of experimental studies. PMID:18332230

  9. Breast feeding twins and high multiples.

    PubMed

    Flidel-Rimon, O; Shinwell, E S

    2006-09-01

    Breast feeding offers major health advantages for all infants, whether born singleton or from multiple pregnancy. Adequate quantity and quality of milk production has been documented even for high multiples. Combined efforts of parents, close family, friends, and the medical team can help to make either full or partial breast feeding of multiples possible.

  10. The Many Meanings of "Multiple Measures"

    ERIC Educational Resources Information Center

    Brookhart, Susan M.

    2009-01-01

    Professional assessment organizations almost universally endorse the use of multiple measures for making education decisions. In practice, however, the concept of multiple measures is defined and applied in many different ways, depending on how we answer two questions--What counts as a "measure"? and How are the multiple measures combined?…

  11. Moist heat intraluminal disinfection of CAPD connectors.

    PubMed

    Fessia, S L; Grabowy, R S; Bousquet, G G

    1990-01-01

    A moist heat technique for disinfecting the inner lumen of commercially available connectology used in the exchange process for Continuous Ambulatory Peritoneal Dialysis (CAPD) was evaluated. Moist heat was generated by a device (PDM-1) that directed microwave energy to heat a sample solution containing a concentration of 10(6) microorganisms inside a pair of mated plastic CAPD connectors. Microorganisms tested included those most prevalent and most problematic in causing peritonitis. Testing, performed according to F.D.A. approved standards, involved heating a sample solution and then placing the sample solution into vials which were then sealed and incubated. Absolute determination of growth versus no growth was measured by macroscopic observation. Positive control samples were performed in the same manner but were not exposed to heat. Negative controls were performed in the same manner in the absence of test organisms. At temperatures of approximately 100 degrees C a D-value of 6.6 seconds was determined using the organism found the most thermoresistant. A cycle time of 54 seconds appeared sufficient to achieve a 10(6) population reduction of all microorganisms tested. The moist heat technique offers a safe, effective method for disinfection of the inner lumen of CAPD connectors. PMID:1982800

  12. [Multiple apheresis].

    PubMed

    Coffe, C

    2007-05-01

    Multiple apheresis makes it possible to obtain at least two labile blood components from a single donor using a cell separator. It can be either multicomponent apheresis leading to the preparation of at least two different blood component types or red blood cell apheresis providing two identical red blood cell concentrates. These techniques available in addition to whole blood donation, are modifying collection strategies in many Etablissements Français du Sang and will contribute to improve stock logistics in the future. In areas with insufficient stock, these procedures will help achieve blood component self-sufficiency. The author first describes the principle underlying different--current or future--techniques as well as their advantages and drawbacks. He finally addresses the potential impact of these processes on the evolution of blood collection and the advantages to be gained. PMID:17521944

  13. Combination Vaccines

    PubMed Central

    Skibinski, David AG; Baudner, Barbara C; Singh, Manmohan; O’Hagan, Derek T

    2011-01-01

    The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of these combinations encountered numerous challenges, including the reduced response to Haemophilus influenzae vaccine when given in combination; the need to consolidate the differences in the immunization schedule (hepatitis B); and the need to improve the safety profile of the diphtheria, tetanus, and pertussis combination. Here, we review these challenges and also discuss future prospects for combination vaccines. PMID:21572611

  14. Power combiner

    SciTech Connect

    Arnold, Mobius; Ives, Robert Lawrence

    2006-09-05

    A power combiner for the combining of symmetric and asymmetric traveling wave energy comprises a feed waveguide having an input port and a launching port, a reflector for reflecting launched wave energy, and a final waveguide for the collection and transport of launched wave energy. The power combiner has a launching port for symmetrical waves which comprises a cylindrical section coaxial to the feed waveguide, and a launching port for asymmetric waves which comprises a sawtooth rotated about a central axis.

  15. Multiple sclerosis

    PubMed Central

    Boster, Aaron L.; Racke, Michael K.

    2013-01-01

    Summary Preliminary studies have suggested that a high salt diet may play a role in the development of autoimmune disease and possibly multiple sclerosis (MS). Promising clinical trial results for 2 new therapies for MS have been reported. Dimethyl fumarate, also known by its investigational name BG-12, became the third oral disease-modifying therapy for MS to be Food and Drug Administration (FDA)–approved in March 2013. Interestingly, dimethyl fumarate served as the active compound used for the treatment of psoriasis for decades. Alemtuzumab remains under investigation and is not currently FDA-approved for treatment of MS. Other drugs currently approved for alternative indications are being investigated for use in MS. Additionally, an investigation of alternative dosing strategies for glatiramer acetate suggests that patients may benefit from a higher dose formulation and less frequent medication administration. Advances in basic science research have identified another potential autoantigenic target in MS, KIR4.1, which may provide further insight into MS pathophysiology. PMID:24175156

  16. Multiple symbol differential detection

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush (Inventor); Simon, Marvin K. (Inventor)

    1991-01-01

    A differential detection technique for multiple phase shift keying (MPSK) signals is provided which uses a multiple symbol observation interval on the basis of which a joint decision is made regarding the phase of the received symbols. In accordance with the invention, a first difference phase is created between first and second received symbols. Next, the first difference phase is correlated with the possible values thereof to provide a first plurality of intermediate output signals. A second difference phase is next created between second and third received symbols. The second difference phase is correlated with plural possible values thereof to provide a second plurality of intermediate output signals. Next, a third difference phase is created between the first and third symbols. The third difference phase is correlated with plural possible values thereof to provide a third plurality of intermediate output signals. Each of the first plurality of intermediate outputs are combined with each of the second plurality of intermediate outputs and each of the third plurality of intermediate outputs to provide a plurality of possible output values. Finally, a joint decision is made by choosing from the plurality of possible output values the value which represents the best combined correlation of the first, second and third difference values with the possible values thereof.

  17. Multiple quantum coherence spectroscopy.

    PubMed

    Mathew, Nathan A; Yurs, Lena A; Block, Stephen B; Pakoulev, Andrei V; Kornau, Kathryn M; Wright, John C

    2009-08-20

    Multiple quantum coherences provide a powerful approach for studies of complex systems because increasing the number of quantum states in a quantum mechanical superposition state increases the selectivity of a spectroscopic measurement. We show that frequency domain multiple quantum coherence multidimensional spectroscopy can create these superposition states using different frequency excitation pulses. The superposition state is created using two excitation frequencies to excite the symmetric and asymmetric stretch modes in a rhodium dicarbonyl chelate and the dynamic Stark effect to climb the vibrational ladders involving different overtone and combination band states. A monochromator resolves the free induction decay of different coherences comprising the superposition state. The three spectral dimensions provide the selectivity required to observe 19 different spectral features associated with fully coherent nonlinear processes involving up to 11 interactions with the excitation fields. The different features act as spectroscopic probes of the diagonal and off-diagonal parts of the molecular potential energy hypersurface. This approach can be considered as a coherent pump-probe spectroscopy where the pump is a series of excitation pulses that prepares a multiple quantum coherence and the probe is another series of pulses that creates the output coherence. PMID:19507812

  18. Multiple System Atrophy

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Multiple System Atrophy Information Page Condensed from Multiple System Atrophy ... Trials Organizations Publicaciones en Español What is Multiple System Atrophy? Multiple system atrophy (MSA) is a progressive ...

  19. Multiple sclerosis - resources

    MedlinePlus

    Resources - multiple sclerosis ... The following organizations provide information on multiple sclerosis : Multiple Sclerosis Foundation -- www.msfocus.org National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/multiple_sclerosis National ...

  20. Successful resection of giant esophageal liposarcoma by endoscopic submucosal dissection combined with surgical retrieval: a case report and literature review.

    PubMed

    Takiguchi, Gosuke; Nakamura, Tetsu; Otowa, Yasunori; Tomono, Ayako; Kanaji, Shingo; Oshikiri, Taro; Suzuki, Satoshi; Ishida, Tsukasa; Kakeji, Yoshihiro

    2016-12-01

    Liposarcoma of the esophagus is very rare. We experienced a huge (27.5 × 11.6 cm) liposarcoma of the esophagus. A 73-year-old man presented with severe dyspnea requiring emergency tracheal intubation. Computed tomography and esophagogastroduodenoscopy showed a large submucosal tumor arising from the esophageal entrance and extending intraluminally to the lower esophagus. We successfully performed endoscopic submucosal dissection (ESD) and esophagotomy to remove the tumor, which preserved swallowing and phonation. The final diagnosis by histopathologic and immunohistologic examination was well-differentiated liposarcoma of the esophagus. Treatment by the combination of ESD and esophagotomy can be performed even for a very large tumor. This method preserves deglutition with a lower risk of recurrent laryngeal nerve paralysis than that with esophagectomy. PMID:27589985

  1. Successful resection of giant esophageal liposarcoma by endoscopic submucosal dissection combined with surgical retrieval: a case report and literature review.

    PubMed

    Takiguchi, Gosuke; Nakamura, Tetsu; Otowa, Yasunori; Tomono, Ayako; Kanaji, Shingo; Oshikiri, Taro; Suzuki, Satoshi; Ishida, Tsukasa; Kakeji, Yoshihiro

    2016-12-01

    Liposarcoma of the esophagus is very rare. We experienced a huge (27.5 × 11.6 cm) liposarcoma of the esophagus. A 73-year-old man presented with severe dyspnea requiring emergency tracheal intubation. Computed tomography and esophagogastroduodenoscopy showed a large submucosal tumor arising from the esophageal entrance and extending intraluminally to the lower esophagus. We successfully performed endoscopic submucosal dissection (ESD) and esophagotomy to remove the tumor, which preserved swallowing and phonation. The final diagnosis by histopathologic and immunohistologic examination was well-differentiated liposarcoma of the esophagus. Treatment by the combination of ESD and esophagotomy can be performed even for a very large tumor. This method preserves deglutition with a lower risk of recurrent laryngeal nerve paralysis than that with esophagectomy.

  2. Drugs Approved for Multiple Myeloma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for multiple myeloma and other plasma cell neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  3. Multiple Segment Factorial Vignette Designs

    ERIC Educational Resources Information Center

    Ganong, Lawrence H.; Coleman, Marilyn

    2006-01-01

    The multiple segment factorial vignette design (MSFV) combines elements of experimental designs and probability sampling with the inductive, exploratory approach of qualitative research. MSFVs allow researchers to investigate topics that may be hard to study because of ethical or logistical concerns. Participants are presented with short stories…

  4. [Fixed-dose combination].

    PubMed

    Nagai, Yoshio

    2015-03-01

    Many patients with type 2 diabetes mellitus(T2DM) do not achieve satisfactory glycemic control by monotherapy alone, and often require multiple oral hypoglycemic agents (OHAs). Combining OHAs with complementary mechanisms of action is fundamental to the management of T2DM. Fixed-dose combination therapy(FDC) offers a method of simplifying complex regimens. Efficacy and tolerability appear to be similar between FDC and treatment with individual agents. In addition, FDC can enhance adherence and improved adherence may result in improved glycemic control. Four FDC agents are available in Japan: pioglitazone-glimepiride, pioglitazone-metformin, pioglitazone-alogliptin, and voglibose-mitiglinide. In this review, the advantages and disadvantages of these four combinations are identified and discussed. PMID:25812374

  5. Combinations Therapies.

    PubMed

    Reinmuth, Niels; Reck, Martin

    2015-01-01

    Immunotherapy of cancer encompasses different strategies that elicit or enhance the immune response against tumors. The first results from clinical studies have provided promising data for the treatment of lung cancer patients with immunomodulating monotherapies. To improve the potential benefit of cancer immunotherapy, synergistic combinations of the various immunotherapy approaches or of different elements within each of the immunotherapy approaches are being explored. The rationale typically involves different but complementary mechanisms of action, eventually impinging on more than one immune system mechanism. As a prominent example, the simultaneous blockade of PD-1 and CTLA-4 is giving rise to therapeutic synergy, while still offering room for efficacy improvement. Moreover, combinations of immunomodulating agents with chemotherapy or targeted molecules are being tested. Animal models suggest that immunotherapies in combination with these various options offer evidence for synergistic effects and are likely to radically change cancer treatment paradigms. However, data obtained so far indicate that toxic side effects are also potentiated, which may even restrict the selection of patients that are suitable for these combinational approaches. Advancing the field of combinatorial immunotherapy will require changes in the way investigational agents are clinically developed as well as novel experimental end-points for efficacy evaluation. However, this combined therapeutic manipulation of both tumor and stromal cells may lead to a dramatic change in the therapeutic options of lung cancer patients in any disease stage that can only grossly be appreciated by the current studies. PMID:26384009

  6. Optical Communications Channel Combiner

    NASA Technical Reports Server (NTRS)

    Quirk, Kevin J.; Quirk, Kevin J.; Nguyen, Danh H.; Nguyen, Huy

    2012-01-01

    NASA has identified deep-space optical communications links as an integral part of a unified space communication network in order to provide data rates in excess of 100 Mb/s. The distances and limited power inherent in a deep-space optical downlink necessitate the use of photon-counting detectors and a power-efficient modulation such as pulse position modulation (PPM). For the output of each photodetector, whether from a separate telescope or a portion of the detection area, a communication receiver estimates a log-likelihood ratio for each PPM slot. To realize the full effective aperture of these receivers, their outputs must be combined prior to information decoding. A channel combiner was developed to synchronize the log-likelihood ratio (LLR) sequences of multiple receivers, and then combines these into a single LLR sequence for information decoding. The channel combiner synchronizes the LLR sequences of up to three receivers and then combines these into a single LLR sequence for output. The channel combiner has three channel inputs, each of which takes as input a sequence of four-bit LLRs for each PPM slot in a codeword via a XAUI 10 Gb/s quad optical fiber interface. The cross-correlation between the channels LLR time series are calculated and used to synchronize the sequences prior to combining. The output of the channel combiner is a sequence of four-bit LLRs for each PPM slot in a codeword via a XAUI 10 Gb/s quad optical fiber interface. The unit is controlled through a 1 Gb/s Ethernet UDP/IP interface. A deep-space optical communication link has not yet been demonstrated. This ground-station channel combiner was developed to demonstrate this capability and is unique in its ability to process such a signal.

  7. Seeing is believing: video classification for computed tomographic colonography using multiple-instance learning.

    PubMed

    Wang, Shijun; McKenna, Matthew T; Nguyen, Tan B; Burns, Joseph E; Petrick, Nicholas; Sahiner, Berkman; Summers, Ronald M

    2012-05-01

    In this paper, we present development and testing results for a novel colonic polyp classification method for use as part of a computed tomographic colonography (CTC) computer-aided detection (CAD) system. Inspired by the interpretative methodology of radiologists using 3-D fly-through mode in CTC reading, we have developed an algorithm which utilizes sequences of images (referred to here as videos) for classification of CAD marks. For each CAD mark, we created a video composed of a series of intraluminal, volume-rendered images visualizing the detection from multiple viewpoints. We then framed the video classification question as a multiple-instance learning (MIL) problem. Since a positive (negative) bag may contain negative (positive) instances, which in our case depends on the viewing angles and camera distance to the target, we developed a novel MIL paradigm to accommodate this class of problems. We solved the new MIL problem by maximizing a L2-norm soft margin using semidefinite programming, which can optimize relevant parameters automatically. We tested our method by analyzing a CTC data set obtained from 50 patients from three medical centers. Our proposed method showed significantly better performance compared with several traditional MIL methods. PMID:22552333

  8. Comparison of pharmacokinetic behavior of two iridoid glycosides in rat plasma after oral administration of crude Cornus officinals and its jiuzhipin by high performance liquid chromatography triple quadrupole mass spectrometry combined with multiple reactions monitoring mode

    PubMed Central

    Chen, Xiaocheng; Cao, Gang; Jiang, Jianping

    2014-01-01

    Objective: The present study examined the pharmacokinetic profiles of two iridoid glycosides named morroniside and loganin in rat plasma after oral administration of crude and processed Cornus officinals. Materials and Methods: A rapid, selective and specific high-performance liquid chromatography/electrospray ionization tandem mass spectrometry with multiple reactions monitoring mode was developed to simultaneously investigate the pharmacokinetic profiles of morroniside and loganin in rat plasma after oral administration of crude C. officinals and its jiuzhipin. Results: The morroniside and loganin in crude and processed C. officinals could be simultaneously determined within 7.4 min. Linear calibration curves were obtained over the concentration ranges of 45.45-4800 ng/mL for all the analytes. The intra-and inter-day precisions relative standard deviation was lesser than 2.84% and 4.12%, respectively. Conclusion: The pharmacokinetic parameters of two iridoid glucosides were also compared systematically between crude and processed C. officinals. This paper provides the theoretical proofs for further explaining the processing mechanism of Traditional Chinese Medicines. PMID:24914290

  9. Herbs and spices: characterization and quantitation of biologically-active markers for routine quality control by multiple headspace solid-phase microextraction combined with separative or non-separative analysis.

    PubMed

    Sgorbini, Barbara; Bicchi, Carlo; Cagliero, Cecilia; Cordero, Chiara; Liberto, Erica; Rubiolo, Patrizia

    2015-01-01

    Herbs and spices are used worldwide as food flavoring, thus determination of their identity, origin, and quality is mandatory for safe human consumption. An analysis strategy based on separative (HS-SPME-GC-MS) and non-separative (HS-SPME-MS) approaches is proposed for the volatile fraction of herbs and spices, for quality control and to quantify the aromatic markers with a single analysis directly on the plant material as such. Eight-to-ten lots of each of the following herbs/spices were considered: cloves (Syzygium aromaticum (L.) Merr. & Perry), American peppertree (Schinus molle L.), black pepper and white pepper (Piper nigrum L.), rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.). Homogeneity, origin, and chemotypes of the investigated lots of each herb/spice were defined by fingerprinting, through statistical elaboration with principal component analysis (PCA). Characterizing aromatic markers were directly quantified on the solid matrix through multiple headspace extraction-HS-SPME (MHS-SPME). Reliable results were obtained with both separative and non-separative methods (where the latter were applicable); the two were in full agreement, RSD% ranging from 1.8 to 7.7% for eugenol in cloves, 2.2-18.4% for carvacrol+thymol in thyme, and 3.1-16.8% for thujones in sage. PMID:25541091

  10. Herbs and spices: characterization and quantitation of biologically-active markers for routine quality control by multiple headspace solid-phase microextraction combined with separative or non-separative analysis.

    PubMed

    Sgorbini, Barbara; Bicchi, Carlo; Cagliero, Cecilia; Cordero, Chiara; Liberto, Erica; Rubiolo, Patrizia

    2015-01-01

    Herbs and spices are used worldwide as food flavoring, thus determination of their identity, origin, and quality is mandatory for safe human consumption. An analysis strategy based on separative (HS-SPME-GC-MS) and non-separative (HS-SPME-MS) approaches is proposed for the volatile fraction of herbs and spices, for quality control and to quantify the aromatic markers with a single analysis directly on the plant material as such. Eight-to-ten lots of each of the following herbs/spices were considered: cloves (Syzygium aromaticum (L.) Merr. & Perry), American peppertree (Schinus molle L.), black pepper and white pepper (Piper nigrum L.), rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.). Homogeneity, origin, and chemotypes of the investigated lots of each herb/spice were defined by fingerprinting, through statistical elaboration with principal component analysis (PCA). Characterizing aromatic markers were directly quantified on the solid matrix through multiple headspace extraction-HS-SPME (MHS-SPME). Reliable results were obtained with both separative and non-separative methods (where the latter were applicable); the two were in full agreement, RSD% ranging from 1.8 to 7.7% for eugenol in cloves, 2.2-18.4% for carvacrol+thymol in thyme, and 3.1-16.8% for thujones in sage.

  11. Multiple Sources In Ultrapotassic Arc Magmas Inferred From Combined Microthermometry And In-Situ Chemical Analysis Of Melt Inclusions In Olivine And Clinopyroxene Phenocrysts From Batu Tara Volcano, Indonesia

    NASA Astrophysics Data System (ADS)

    Herrin, J. S.; Nikogosian, I. K.; van Bergen, M. J.; Mason, P. R.

    2001-12-01

    Batu Tara is an active, leucite-normative, ultrapotassic volcano located approximately 75 km behind the main magmatic front of the eastern Sunda arc, Indonesia. Clinopyroxene, olivine, plagioclase, leucite, Ti-magnetite, minor apatite and occasional biotite occur as phenocrysts. The exact mechanism for genesis of ultrapotassic arc rocks remains elusive, particularly in island arc settings. Concise determination of primary magma chemistry is often impeded by complex histories of crystallization and magma mixing. Melt inclusions in olivine and pyroxene phenocrysts from Batu Tara have been investigated by high-temperature microthermometry, EPMA, and LA-ICP-MS to constrain parent magma composition and shed light on the genesis of ultrapotassic magmas in island arc settings. Variation in homogenization temperature, major and trace element composition, and volatile content correlate with petrographic observation of three distinct populations of olivine phenocrysts which can be distinguished by the presence or absence of apatite mineral inclusions and CO2 fluid inclusions. Clinopyroxenes commonly exhibit pronounced chemical zonation with individual zones preserving melt inclusions of unique composition, indicating that these phenocrysts were involved in complex mixing processes and repeatedly subject to end-member magma compositions. Melt inclusions preserve a record of; (1) Early spinel, olivine and clinopyroxene crystallization, followed by later crystallization of abundant apatite; (2) Exsolution of volatile species (S, CO2, Cl, H2O) during magma degassing; (3) Mixing of multiple magmas, originating from chemically and likely genetically distinct sources, and; (4) A significant but variable component of fluid addition to the magma source inferred from systematics of incompatible trace elements.

  12. Improved Therapeutic Benefits by Combining Physical Cooling With Pharmacological Hypothermia After Severe Stroke in Rats

    PubMed Central

    Lee, Jin Hwan; Wei, Ling; Gu, Xiaohuan; Won, Soonmi; Wei, Zheng Zachory; Dix, Thomas A.

    2016-01-01

    Background and Purpose— Therapeutic hypothermia is a promising strategy for treatment of acute stroke. Clinical translation of therapeutic hypothermia, however, has been hindered because of the lack of efficiency and adverse effects. We sought to enhance the clinical potential of therapeutic hypothermia by combining physical cooling (PC) with pharmacologically induced hypothermia after ischemic stroke. Methods— Wistar rats were subjected to 90-minute middle cerebral artery occlusion by insertion of an intraluminal filament. Mild-to-moderate hypothermia was induced 120 minutes after the onset of stroke by PC alone, a neurotensin receptor 1 (NTR1) agonist HPI-201 (formally ABS-201) alone or the combination of both. The outcomes of stroke were evaluated at 3 and 21 days after stroke. Results— PC or HPI-201 each showed hypothermic effect and neuroprotection in stroke rats. The combination of PC and HPI-201 exhibited synergistic effects in cooling process, reduced infarct formation, cell death, and blood-brain barrier damages and improved functional recovery after stroke. Importantly, coapplied HPI-201 completely inhibited PC-associated shivering and tachycardia. Conclusions— The centrally acting hypothermic drug HPI-201 greatly enhanced the efficiency and efficacy of conventional PC; this combined cooling therapy may facilitate clinical translation of hypothermic treatment for stroke. PMID:27301934

  13. Diagnostic Molecular Mycobacteriology in Regions With Low Tuberculosis Endemicity: Combining Real-time PCR Assays for Detection of Multiple Mycobacterial Pathogens With Line Probe Assays for Identification of Resistance Mutations.

    PubMed

    Deggim-Messmer, Vanessa; Bloemberg, Guido V; Ritter, Claudia; Voit, Antje; Hömke, Rico; Keller, Peter M; Böttger, Erik C

    2016-07-01

    Molecular assays have not yet been able to replace time-consuming culture-based methods in clinical mycobacteriology. Using 6875 clinical samples and a study period of 35months we evaluated the use of PCR-based assays to establish a diagnostic workflow with a fast time-to-result of 1-2days, for 1. detection of Mycobacterium tuberculosis complex (MTB), 2. detection and identification of nontuberculous mycobacteria (NTM), and 3. identification of drug susceptible MTB. MTB molecular-based detection and culture gave concordant results for 97.7% of the specimens. NTM PCR-based detection and culture gave concordant results for 97.0% of the specimens. Defining specimens on the basis of combined laboratory data as true positives or negatives with discrepant results resolved by clinical chart reviews, we calculated sensitivity, specificity, PPV and NPV for PCR-based MTB detection as 84.7%, 100%, 100%, and 98.7%; the corresponding values for culture-based MTB detection were 86.3%, 100%, 100%, and 98.8%. PCR-based detection of NTM had a sensitivity of 84.7% compared to 78.0% of that of culture-based NTM detection. Molecular drug susceptibility testing (DST) by line-probe assay was found to predict phenotypic DST results in MTB with excellent accuracy. Our findings suggest a diagnostic algorithm to largely replace lengthy culture-based techniques by rapid molecular-based methods.

  14. Combination Light

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The Rayovac TANDEM is an advanced technology combination work light and general purpose flashlight that incorporates several NASA technologies. The TANDEM functions as two lights in one. It features a long range spotlight and wide angle floodlight; simple one-hand electrical switching changes the beam from spot to flood. TANDEM developers made particular use of NASA's extensive research in ergonomics in the TANDEM's angled handle, convenient shape and different orientations. The shatterproof, water resistant plastic casing also draws on NASA technology, as does the shape and beam distance of the square diffused flood. TANDEM's heavy duty magnet that permits the light to be affixed to any metal object borrows from NASA research on rare earth magnets that combine strong magnetic capability with low cost. Developers used a NASA-developed ultrasonic welding technique in the light's interior.

  15. Multiple acousto-optic q-switch

    SciTech Connect

    Deason, Vance A.

    1993-01-01

    An improved dynamic moire interferometer comprised of a lasing medium providing a plurality of beams of coherent light, a multiple q-switch producing multiple trains of 100,000 or more pulses per second, a combining means collimating multiple trains of pulses into substantially a single train and directing beams to specimen gratings affixed to a test material, and a controller, triggering and sequencing the emission of the pulses with the occurrence and recording of a dynamic loading event.

  16. Multiple acousto-optic q-switch

    SciTech Connect

    Deason, Vance A.

    1993-12-07

    An improved dynamic moire interferometer comprised of a lasing medium providing a plurality of beams of coherent light, a multiple q-switch producing multiple trains of 100,000 or more pulses per second, a combining means collimating multiple trains of pulses into substantially a single train and directing beams to specimen gratings affixed to a test material, and a controller, triggering and sequencing the emission of the pulses with the occurrence and recording of a dynamic loading event.

  17. Mixed Mode Matrix Multiplication

    SciTech Connect

    Meng-Shiou Wu; Srinivas Aluru; Ricky A. Kendall

    2004-09-30

    In modern clustering environments where the memory hierarchy has many layers (distributed memory, shared memory layer, cache,...), an important question is how to fully utilize all available resources and identify the most dominant layer in certain computations. When combining algorithms on all layers together, what would be the best method to get the best performance out of all the resources we have? Mixed mode programming model that uses thread programming on the shared memory layer and message passing programming on the distributed memory layer is a method that many researchers are using to utilize the memory resources. In this paper, they take an algorithmic approach that uses matrix multiplication as a tool to show how cache algorithms affect the performance of both shared memory and distributed memory algorithms. They show that with good underlying cache algorithm, overall performance is stable. When underlying cache algorithm is bad, superlinear speedup may occur, and an increasing number of threads may also improve performance.

  18. Constructive Multiple-Choice Testing System

    ERIC Educational Resources Information Center

    Park, Jooyong

    2010-01-01

    The newly developed computerized Constructive Multiple-choice Testing system is introduced. The system combines short answer (SA) and multiple-choice (MC) formats by asking examinees to respond to the same question twice, first in the SA format, and then in the MC format. This manipulation was employed to collect information about the two…

  19. Multiple sequence alignment with DIALIGN.

    PubMed

    Morgenstern, Burkhard

    2014-01-01

    DIALIGN is a software tool for multiple sequence alignment by combining global and local alignment features. It composes multiple alignments from local pairwise sequence similarities. This approach is particularly useful to discover conserved functional regions in sequences that share only local homologies but are otherwise unrelated. An anchoring option allows to use external information and expert knowledge in addition to primary-sequence similarity alone. The latest version of DIALIGN optionally uses matches to the PFAM database to detect weak homologies. Various versions of the program are available through Göttingen Bioinformatics Compute Server (GOBICS) at http://www.gobics.de/department/software.

  20. Multiple organ dysfunction syndrome.

    PubMed

    Ramírez, Michelle

    2013-01-01

    Initially known as multiple system organ failure, the term multiple organ dysfunction syndrome (MODS) was first described in the 1960s in adults with bleeding, respiratory failure, and sepsis. It is defined as "the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life threatening physiologic insult."(3) There are many risk factors predisposing to MODS; however, the most common risk factors are shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune response, or immuneparalysis, in which the homeostasis between pro-inflammatory and anti-inflammatory reaction is lost is thought to be key in the development of MODS. The clinical course and evolution of MODS is dependent on a combination of acquired and genetic factors. There are several nonspecific therapies for the prevention and resolution of MODS, mostly care is supportive. Mortality from MODS in septic pediatric patients varies between 11% and 54%.

  1. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis.

    PubMed

    Langford, R M; Mares, J; Novotna, A; Vachova, M; Novakova, I; Notcutt, W; Ratcliffe, S

    2013-04-01

    Central neuropathic pain (CNP) occurs in many multiple sclerosis (MS) patients. The provision of adequate pain relief to these patients can very difficult. Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (USAN name, nabiximols; Sativex, GW Pharmaceuticals, Salisbury, Wiltshire, UK), to alleviate CNP. Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment, in a double-blind manner, for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain. This parallel-group phase of the study was then followed by an 18-week randomized-withdrawal study (14-week open-label treatment period plus a double-blind 4-week randomized-withdrawal phase) to investigate time to treatment failure and show maintenance of efficacy. A total of 339 patients were randomized to phase A (167 received THC/CBD spray and 172 received placebo). Of those who completed phase A, 58 entered the randomized-withdrawal phase. The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met, with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo (p = 0.234). However, an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point (p = 0.046). During the randomized-withdrawal phase, the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray, with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group (p = 0.04). The mean change from baseline in Pain Numerical Rating Scale (NRS) (p = 0.028) and sleep quality NRS (p = 0.015) scores, both secondary endpoints in phase B, were also statistically

  2. Multiple tumours in survival estimates.

    PubMed

    Rosso, Stefano; De Angelis, Roberta; Ciccolallo, Laura; Carrani, Eugenio; Soerjomataram, Isabelle; Grande, Enrico; Zigon, Giulia; Brenner, Hermann

    2009-04-01

    In international comparisons of cancer registry based survival it is common practice to restrict the analysis to first primary tumours and exclude multiple cancers. The probability of correctly detecting subsequent cancers depends on the registry's running time, which results in different proportions of excluded patients and may lead to biased comparisons. We evaluated the impact on the age-standardised relative survival estimates of also including multiple primary tumours. Data from 2,919,023 malignant cancers from 69 European cancer registries participating in the EUROCARE-4 collaborative study were used. A total of 183,683 multiple primary tumours were found, with an overall proportion of 6.3% over all the considered cancers, ranging from 0.4% (Naples, Italy) to 12.9% (Iceland). The proportion of multiple tumours varied greatly by type of tumour, being higher for those with high incidence and long survival (breast, prostate and colon-rectum). Five-year relative survival was lower when including patients with multiple cancers. For all cancers combined the average difference was -0.4 percentage points in women and -0.7 percentage points in men, and was greater for older registries. Inclusion of multiple tumours led to lower survival in 44 out of 45 cancer sites analysed, with the greatest differences found for larynx (-1.9%), oropharynx (-1.5%), and penis (-1.3%). Including multiple primary tumours in survival estimates for international comparison is advisable because it reduces the bias due to different observation periods, age, registration quality and completeness of registration. The general effect of inclusion is to reduce survival estimates by a variable amount depending on the proportion of multiple primaries and cancer site.

  3. Developments in multiple headspace extraction.

    PubMed

    Hakkarainen, Minna

    2007-03-10

    This paper reviews new developments in multiple headspace extraction (MHE), especially its combination with two miniaturized extraction techniques, solid-phase microextraction (SPME) and single-drop microextraction (SDME). The combination of the techniques broadens the applicability of SPME and SDME to quantitative determination of analytes in complex liquid and solid matrixes. These new methods offer several advantages over traditional liquid-solid, liquid-liquid and headspace extraction techniques. The potential applications include extraction of volatiles and semivolatiles from environmental and physiological samples and from different polymer products such as medical and biomedical materials, food packaging and building materials. The theoretical principals of the techniques are also briefly reviewed. PMID:17081616

  4. Prevalence of extracranial venous abnormalities: results from a sample of 586 multiple sclerosis patients

    PubMed Central

    Simka, Marian; Latacz, Pawel; Ludyga, Tomasz; Kazibudzki, Marek; Świerad, Marcin; Janas, Piotr; Piegza, Jacek

    Summary The aim of this study was to assess the prevalence of chronic cerebrospinal venous insufficiency in an unselected cohort of multiple sclerosis (MS) patients. A total of 586 patients with clinically defined MS underwent catheter venography of the internal jugular veins, brachiocephalic veins and azygos vein. The following findings were regarded as pathologic: no outflow, slowed outflow, reversal of flow direction, prestenotic dilation accompanied by impaired outflow, outflow through collaterals, intraluminal structures obstructing the vein, hypoplasia, agenesia or significant narrowing of the vein. Venous abnormalities were found in 563 patients (96.1%). Lesions in one vein were found in 43.5%, in two veins in 49.5%, and in three veins in 3.1% of patients. Venous pathologies in the right internal jugular vein were found in 64.0% of patients, in the left internal jugular vein in 81.7%, in the left brachiocephalic vein in 1.0%, and in the azygos vein in 4.9%. Venous pathologies were found to be highly associated with MS, yet the clinical relevance of this phenomenon remains to be established. PMID:22364940

  5. Prevalence of extracranial venous abnormalities: results from a sample of 586 multiple sclerosis patients.

    PubMed

    Simka, M; Latacz, P; Ludyga, T; Kazibudzki, M; Swierad, M; Janas, P; Piegza, J

    2011-01-01

    The aim of this study was to assess the prevalence of chronic cerebrospinal venous insufficiency in an unselected cohort of multiple sclerosis (MS) patients. A total of 586 patients with clinically defined MS underwent catheter venography of the internal jugular veins, brachiocephalic veins and azygos vein. The following findings were regarded as pathologic: no outflow, slowed outflow, reversal of flow direction, prestenotic dilation accompanied by impaired outflow, outflow through collaterals, intraluminal structures obstructing the vein, hypoplasia, agenesia or significant narrowing of the vein. Venous abnormalities were found in 563 patients (96.1%). Lesions in one vein were found in 43.5%, in two veins in 49.5%, and in three veins in 3.1% of patients. Venous pathologies in the right internal jugular vein were found in 64.0% of patients, in the left internal jugular vein in 81.7%, in the left brachiocephalic vein in 1.0%, and in the azygos vein in 4.9%. Venous pathologies were found to be highly associated with MS, yet the clinical relevance of this phenomenon remains to be established.

  6. [Non-contrast time-resolved magnetic resonance angiography combining high resolution multiple phase echo planar imaging based signal targeting and alternating radiofrequency contrast inherent inflow enhanced multi phase angiography combining spatial resolution echo planar imaging based signal targeting and alternating radiofrequency in intracranial arteries].

    PubMed

    Nakamura, Masanobu; Yoneyama, Masami; Tabuchi, Takashi; Takemura, Atsushi; Obara, Makoto; Sawano, Seishi

    2012-01-01

    Detailed information on anatomy and hemodynamics in cerebrovascular disorders such as AVM and Moyamoya disease is mandatory for defined diagnosis and treatment planning. Arterial spin labeling technique has come to be applied to magnetic resonance angiography (MRA) and perfusion imaging in recent years. However, those non-contrast techniques are mostly limited to single frame images. Recently we have proposed a non-contrast time-resolved MRA technique termed contrast inherent inflow enhanced multi phase angiography combining spatial resolution echo planar imaging based signal targeting and alternating radiofrequency (CINEMA-STAR). CINEMA-STAR can extract the blood flow in the major intracranial arteries at an interval of 70 ms and thus permits us to observe vascular construction in full by preparing MIP images of axial acquisitions with high spatial resolution. This preliminary study demonstrates the usefulness of the CINEMA-STAR technique in evaluating the cerebral vasculature.

  7. Bayes multiple decision functions.

    PubMed

    Wu, Wensong; Peña, Edsel A

    2013-01-01

    This paper deals with the problem of simultaneously making many (M) binary decisions based on one realization of a random data matrix X. M is typically large and X will usually have M rows associated with each of the M decisions to make, but for each row the data may be low dimensional. Such problems arise in many practical areas such as the biological and medical sciences, where the available dataset is from microarrays or other high-throughput technology and with the goal being to decide which among of many genes are relevant with respect to some phenotype of interest; in the engineering and reliability sciences; in astronomy; in education; and in business. A Bayesian decision-theoretic approach to this problem is implemented with the overall loss function being a cost-weighted linear combination of Type I and Type II loss functions. The class of loss functions considered allows for use of the false discovery rate (FDR), false nondiscovery rate (FNR), and missed discovery rate (MDR) in assessing the quality of decision. Through this Bayesian paradigm, the Bayes multiple decision function (BMDF) is derived and an efficient algorithm to obtain the optimal Bayes action is described. In contrast to many works in the literature where the rows of the matrix X are assumed to be stochastically independent, we allow a dependent data structure with the associations obtained through a class of frailty-induced Archimedean copulas. In particular, non-Gaussian dependent data structure, which is typical with failure-time data, can be entertained. The numerical implementation of the determination of the Bayes optimal action is facilitated through sequential Monte Carlo techniques. The theory developed could also be extended to the problem of multiple hypotheses testing, multiple classification and prediction, and high-dimensional variable selection. The proposed procedure is illustrated for the simple versus simple hypotheses setting and for the composite hypotheses setting

  8. Process for combining multiple passes of interferometric SAR data

    DOEpatents

    Bickel, Douglas L.; Yocky, David A.; Hensley, Jr., William H.

    2000-11-21

    Interferometric synthetic aperture radar (IFSAR) is a promising technology for a wide variety of military and civilian elevation modeling requirements. IFSAR extends traditional two dimensional SAR processing to three dimensions by utilizing the phase difference between two SAR images taken from different elevation positions to determine an angle of arrival for each pixel in the scene. This angle, together with the two-dimensional location information in the traditional SAR image, can be transformed into geographic coordinates if the position and motion parameters of the antennas are known accurately.

  9. Assisting People with Multiple Disabilities to Use Computers with Multiple Mice

    ERIC Educational Resources Information Center

    Shih, Ching-Hsiang; Shih, Ching-Tien

    2009-01-01

    This study assessed the combination of multiple mice aid with two persons with multiple disabilities. Complete mouse operation which needed the physically functional sound, was distributed among their limbs with remaining ability. Through these decentralized operations, they could still reach complete mouse pointing control. Initially, both…

  10. Adaptive marker-free registration using a multiple point strategy for real-time and robust endoscope electromagnetic navigation.

    PubMed

    Luo, Xiongbiao; Wan, Ying; He, Xiangjian; Mori, Kensaku

    2015-02-01

    Registration of pre-clinical images to physical space is indispensable for computer-assisted endoscopic interventions in operating rooms. Electromagnetically navigated endoscopic interventions are increasingly performed at current diagnoses and treatments. Such interventions use an electromagnetic tracker with a miniature sensor that is usually attached at an endoscope distal tip to real time track endoscope movements in a pre-clinical image space. Spatial alignment between the electromagnetic tracker (or sensor) and pre-clinical images must be performed to navigate the endoscope to target regions. This paper proposes an adaptive marker-free registration method that uses a multiple point selection strategy. This method seeks to address an assumption that the endoscope is operated along the centerline of an intraluminal organ which is easily violated during interventions. We introduce an adaptive strategy that generates multiple points in terms of sensor measurements and endoscope tip center calibration. From these generated points, we adaptively choose the optimal point, which is the closest to its assigned the centerline of the hollow organ, to perform registration. The experimental results demonstrate that our proposed adaptive strategy significantly reduced the target registration error from 5.32 to 2.59 mm in static phantoms validation, as well as from at least 7.58 mm to 4.71 mm in dynamic phantom validation compared to current available methods.

  11. Multiple-Ring Digital Communication Network

    NASA Technical Reports Server (NTRS)

    Kirkham, Harold

    1992-01-01

    Optical-fiber digital communication network to support data-acquisition and control functions of electric-power-distribution networks. Optical-fiber links of communication network follow power-distribution routes. Since fiber crosses open power switches, communication network includes multiple interconnected loops with occasional spurs. At each intersection node is needed. Nodes of communication network include power-distribution substations and power-controlling units. In addition to serving data acquisition and control functions, each node acts as repeater, passing on messages to next node(s). Multiple-ring communication network operates on new AbNET protocol and features fiber-optic communication.

  12. Multiple valence superatoms.

    PubMed

    Reveles, J U; Khanna, S N; Roach, P J; Castleman, A W

    2006-12-01

    We recently demonstrated that, in gas phase clusters containing aluminum and iodine atoms, an Al(13) cluster behaves like a halogen atom, whereas an Al(14) cluster exhibits properties analogous to an alkaline earth atom. These observations, together with our findings that Al(13)(-) is inert like a rare gas atom, have reinforced the idea that chosen clusters can exhibit chemical behaviors reminiscent of atoms in the periodic table, offering the exciting prospect of a new dimension of the periodic table formed by cluster elements, called superatoms. As the behavior of clusters can be controlled by size and composition, the superatoms offer the potential to create unique compounds with tailored properties. In this article, we provide evidence of an additional class of superatoms, namely Al(7)(-), that exhibit multiple valences, like some of the elements in the periodic table, and hence have the potential to form stable compounds when combined with other atoms. These findings support the contention that there should be no limitation in finding clusters, which mimic virtually all members of the periodic table.

  13. Multiple valence superatoms

    PubMed Central

    Reveles, J. U.; Khanna, S. N.; Roach, P. J.; Castleman, A. W.

    2006-01-01

    We recently demonstrated that, in gas phase clusters containing aluminum and iodine atoms, an Al13 cluster behaves like a halogen atom, whereas an Al14 cluster exhibits properties analogous to an alkaline earth atom. These observations, together with our findings that Al13− is inert like a rare gas atom, have reinforced the idea that chosen clusters can exhibit chemical behaviors reminiscent of atoms in the periodic table, offering the exciting prospect of a new dimension of the periodic table formed by cluster elements, called superatoms. As the behavior of clusters can be controlled by size and composition, the superatoms offer the potential to create unique compounds with tailored properties. In this article, we provide evidence of an additional class of superatoms, namely Al7−, that exhibit multiple valences, like some of the elements in the periodic table, and hence have the potential to form stable compounds when combined with other atoms. These findings support the contention that there should be no limitation in finding clusters, which mimic virtually all members of the periodic table. PMID:17121987

  14. Fatigue and Multiple Sclerosis

    MedlinePlus

    Fatigue - National Multiple Sclerosis Society Skip to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area ... help* daily life for: positive-mom* The National MS Society is Here to Help Need More Information? ...

  15. What Is Multiple Myeloma?

    MedlinePlus

    ... other tissues. If someone has only a single plasma cell tumor, the disease is called an isolated (or solitary ) plasmacytoma . If someone has more than one plasmacytoma, they have multiple myeloma . Multiple myeloma is ...

  16. Challenges of Parenting Multiples

    MedlinePlus

    ... Parenting Multiples There are many psychological, social, and economic issues associated with multiple pregnancies. These issues should ... births can also be helpful during difficult times. ECONOMIC ISSUES • The health care cost for delivery and ...

  17. National Multiple Sclerosis Society

    MedlinePlus

    ... Join the Community Stay Informed Corporate Support National Multiple Sclerosis Society Our Mission: People affected by MS can ... 10.5 Million in New Research to Stop Multiple Sclerosis, Restore Function and End MS Forever October 11, ...

  18. MultipleColposcopyJCO

    Cancer.gov

    Performing multiple biopsies during a procedure known as colposcopy—visual inspection of the cervix—is more effective than performing only a single biopsy of the worst-appearing area for detecting cervical cancer precursors. This multiple biopsy approach

  19. Multiple Endocrine Neoplasia Syndromes

    MedlinePlus

    ... or cancerous (malignant) tumors or grow excessively without forming tumors. Multiple endocrine neoplasia syndromes are caused by ... This Article Generic Name Select Brand Names corticotropin H.P. ACTHAR GEL epinephrine ADRENALIN Multiple Endocrine Neoplasia ...

  20. On the Performance of Multiple Pulse Multiple Delay UWB Modulation

    SciTech Connect

    Nekoogar, F; Dowla, F U

    2003-05-23

    Multiple access (MA) in UWB communication is an area of active research. In this paper we introduce and study the performance of a new MA scheme in the context of multiple transmitted-reference short duration (nsec) chirp pulses in the presence of additive white Gaussian noise (AWGN). The transmitted-reference (T-R) receiver is extended using multiple orthogonal pulses. The proposed UWB receiver samples the receiver autocorrelation function (ACF) at both zero- and non-zero lags, thus sampling and matching the shape of ACFs rather than just the shape of the received pulses. Sampling of non-zero ACF lags is a significant new approach. The scheme proposed in this paper is a step towards combining the multi-pulse approach and T-R modulation in a multiple access ultra wideband (MA-UWB) communications system. Improved bit error rate performance over a conventional zero-lag receiver (i.e. energy detection receiver) is demonstrated by simulation. Analytical expressions for the system BER are also derived and confirmed through simulations for the system.

  1. 49 CFR 391.63 - Multiple-employer drivers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Multiple-employer drivers. 391.63 Section 391.63... AND LONGER COMBINATION VEHICLE (LCV) DRIVER INSTRUCTORS Limited Exemptions § 391.63 Multiple-employer drivers. (a) If a motor carrier employs a person as a multiple-employer driver (as defined in § 390.5...

  2. Thermodynamics of combined cycle plant

    NASA Astrophysics Data System (ADS)

    Crane, R. I.

    The fundamental thermodynamics of power plants including definitions of performance criteria and an introduction to exergy are reviewed, and treatments of simplified performance calculations for the components which form the major building blocks and a gas/steam combined cycle plant are given: the gas turbine, the heat recovery steam generator, and the remainder of the steam plant. Efficiency relationships and energy and exergy analyses of combined cycle plant are presented, with examples. Among the aspects considered are gas turbine performance characteristics and fuels, temperature differences for heat recovery, multiple steam pressures and reheat, supplementary firing and feed water heating. Attention is drawn to points of thermodynamic interest arising from applications of combined cycle plant to repowering of existing steam plant and to combined heat and power (cogeneration); some advances, including coal firing, are also introduced.

  3. Nutrition for Multiples.

    PubMed

    Luke, Barbara

    2015-09-01

    In 2012 there were 135,943 infants of multiple pregnancies born in the United States, nearly a 2-fold increase since 1980, with twins accounting for 96% of all multiple births. To date, most perinatal morbidities associated with multiple births have proven resistant to technological or pharmaceutical interventions. Maternal nutrition can have a profound effect on the course and outcome of multiple pregnancy, with the goal of achieving optimal intrauterine growth and birthweights, and minimizing prenatal and perinatal complications for the mother and her children.

  4. Multiple primary cancers: An enigma

    PubMed Central

    Jena, Amitabh; Patnayak, Rashmi; Lakshmi, Amancharla Yadagiri; Manilal, Banoth; Reddy, Mandyam Kumaraswamy

    2016-01-01

    Background: Incidence of multiple primary cancers though uncommon, is being frequently reported now-a-days owing to better diagnostic techniques, the prolonged life span and the increased incidence of long-term survival of cancer patients. Materials and Methods: This is a retrospective study. Cases of multiple malignancies diagnosed histopathologically were retrieved from the archives of department of surgical oncology. Clinical data were obtained from the medical records. They were categorized as synchronous malignancies if the interval between them was less or equal to 6 months and metachronous, if the interval was more than 6 months. Results: A total of 13 cases were encountered in the 5 year study period. Out of them two were in the metachronous category and the rest were synchronous as the 2nd malignancy was detected mostly during clinical evaluation of the patients for the primary malignancy. There was female predominance with age range being 43-68 years. Majority of the cases were in the 7th decade. The most common organ involved was breast, followed by cervix. Apart from bilateral breast malignancies, there were combinations like breast with uterine endometrial carcinoma, cervical carcinoma and even papillary thyroid carcinoma. Conclusion: Detection of multiple primary malignancies is becoming increasingly common in day-to-day practice. Greater awareness of this is required among both cancer patients and their treating clinicians. PMID:27169120

  5. Optical multiple object tracking techniques

    NASA Technical Reports Server (NTRS)

    Liu, Hua-Kuang; Chao, Tien-Hsin

    1989-01-01

    Two multichannel multiple-object tracking techniques are reviewed. In the diffraction grating technique, the input scene is picked up by a TV camera and imaged onto a liquid-crystal light valve (LCLV), and the output side of the light valve is illuminated with a suitably polarized and collimated coherent laser beam to yield a reflected beam with polarization modulated according to the intensity of the incoherent input. This reflected beam passes through a beam splitter cube and an analyzer, resulting in an intensity modulated coherent image. An array of spectrum islands containing the information of the input appears after crossing a contact screen/lens combination. In the multiple-focus hololens technique, the scene of moving objects is sent into the LCTVSLM through a camera; a collimated laser beam is incident upon the LCTV screen; a low-pass filter is inserted between the LCTVSLM and the hololens for the removal of the high order diffractions due to the grid structure of the LCTV. The feasibility of the LCTVSLM and multiple-focus hololens technique is demonstrated.

  6. A multiple armature railgun launcher

    NASA Astrophysics Data System (ADS)

    Heyse, Mark W.; Challita, Antonios; Maas, Brian L.; Bauer, David P.

    1993-01-01

    As longer projectiles are accelerated, the efficiency (projectile mass/launch mass) of the launch package decreases. The reduction in efficiency makes launching projectiles with a L/D (length-to-diameter ratio) greater than 20 undesirable. EM guns have several launch characteristics that differ from conventional guns. Higher launch velocities are achievable in EM guns because sonic gas velocities do not limit the projectile velocity. Acceleration profiles for EM guns are more constant. The acceleration forces can be distributed on the projectile easily because the accelerating force can be distributed with multiple armatures. These characteristics combine to make EN guns a very attractive approach for launching very long (i.e.. high L/D ratio) projectiles. Railgun launchers with multiple armatures can distribute the accelerating force. Each armature is supplied gun current for acceleration through its own set of rails. This multi-rail, multi-armature concept was tested at the railgun test facility. The results demonstrated feasibility. We were able to control current distribution to multiple armatures. This paper describes the theory and test results for multi-armature launch of high L/D projectiles.

  7. Multiple density layered insulator

    DOEpatents

    Alger, Terry W.

    1994-01-01

    A multiple density layered insulator for use with a laser is disclosed wh provides at least two different insulation materials for a laser discharge tube, where the two insulation materials have different thermoconductivities. The multiple layer insulation materials provide for improved thermoconductivity capability for improved laser operation.

  8. Multiple density layered insulator

    DOEpatents

    Alger, T.W.

    1994-09-06

    A multiple density layered insulator for use with a laser is disclosed which provides at least two different insulation materials for a laser discharge tube, where the two insulation materials have different thermoconductivities. The multiple layer insulation materials provide for improved thermoconductivity capability for improved laser operation. 4 figs.

  9. Multiple Myeloma Symptoms

    MedlinePlus

    ... it is multiple myeloma . Stay on top of discoveries, trials, research and more. Click here to sign up for the MMRF Newsletter First name Last name E-mail address CLOSE News & Press Multiple Myeloma Knowledge Center Privacy Policy Donor Privacy Policy Terms of ...

  10. Orchestrating Multiple Intelligences

    ERIC Educational Resources Information Center

    Moran, Seana; Kornhaber, Mindy; Gardner, Howard

    2006-01-01

    Education policymakers often go astray when they attempt to integrate multiple intelligences theory into schools, according to the originator of the theory, Howard Gardner, and his colleagues. The greatest potential of a multiple intelligences approach to education grows from the concept of a profile of intelligences. Each learner's intelligence…

  11. Twins, Triplets, Multiple Births

    MedlinePlus

    ... from alone. Multiple births are up in the United States. More women are having babies after age 30 and more are taking fertility drugs. Both boost the chance of carrying more than one baby. A family history of twins also makes multiples more likely. Years ...

  12. Prediction in Multiple Regression.

    ERIC Educational Resources Information Center

    Osborne, Jason W.

    2000-01-01

    Presents the concept of prediction via multiple regression (MR) and discusses the assumptions underlying multiple regression analyses. Also discusses shrinkage, cross-validation, and double cross-validation of prediction equations and describes how to calculate confidence intervals around individual predictions. (SLD)

  13. [Multiple pulmonary hyalinizing granuloma].

    PubMed

    Haro, M; Ruiz, J; Vila, X; Avellanet, M; Izquierdo, J

    1994-01-01

    The causes of multiple pulmonary nodules are many, with metastasis being the most feared. A rare but possible etiology, however, is hyalinizing multiple granuloma. We present a case that allows us to review this condition and its course, as well as a variety of associated immunological changes and possible complications. PMID:8087395

  14. Applying Multiple Intelligences

    ERIC Educational Resources Information Center

    Christodoulou, Joanna A.

    2009-01-01

    The ideas of multiple intelligences introduced by Howard Gardner of Harvard University more than 25 years ago have taken form in many ways, both in schools and in other sometimes-surprising settings. The silver anniversary of Gardner's learning theory provides an opportunity to reflect on the ways multiple intelligences theory has taken form and…

  15. Constraining Multiple Grammars

    ERIC Educational Resources Information Center

    Hopp, Holger

    2014-01-01

    This article offers the author's commentary on the Multiple Grammars (MG) language acquisition theory proposed by Luiz Amaral and Tom Roeper in the present issue. Multiple Grammars advances the claim that optionality is a constitutive characteristic of any one grammar, with interlanguage grammars being perhaps the clearest examples of a…

  16. Current multiplication by using multiple thyristors.

    PubMed

    Liu, Z; Pemen, A J M; Van Heesch, E J M; Winands, G J J

    2008-07-01

    This paper presents a circuit topology to obtain current multiplication by using multiple thyristors. To gain insight into this technique, an equivalent circuit model is introduced. Proper operation of the topology was demonstrated by experiments on a small-scale setup including three thyristors. One thyristor is triggered by a trigger circuit; the other two are autotriggered and require no external trigger circuit. The three thyristors could be synchronized automatically in sequence. During the closing process, the discharging of the energy storage capacitors via the thyristors is prevented. The discharging starts when all thyristors are closed, and the currents through each thyristor are simultaneous and identical. The output current is exactly three times the switching current.

  17. Kamishibai: A Vehicle to Multiple Literacies.

    ERIC Educational Resources Information Center

    Lee, Gretchen

    2003-01-01

    Outlines how the author and her fellow history teacher used kamishibai storyboards (a type of folk art common in Japan before World War II) in an integrated unit on Egypt to make textbook reading more meaningful to students. Notes that in order to complete the unit, students had to use multiple literacy skills as they combined textbook reading…

  18. Multiple Output Sensory Trainer (MOST). Final Report.

    ERIC Educational Resources Information Center

    Automated Functions, Inc., Arlington, VA.

    This final report describes the design, development, and testing of the Multiple Output Sensory Trainer (MOST), a computer-based system which enables the evaluation of students with visual impairments to determine the optimal combination of sensory adaptive aids to meet their needs. The system uses multimedia devices in conjunction with customized…

  19. Advanced Multiple Processor Configuration Study. Final Report.

    ERIC Educational Resources Information Center

    Clymer, S. J.

    This summary of a study on multiple processor configurations includes the objectives, background, approach, and results of research undertaken to provide the Air Force with a generalized model of computer processor combinations for use in the evaluation of proposed flight training simulator computational designs. An analysis of a real-time flight…

  20. Multiple Input Microcantilever Sensor with Capacitive Readout

    SciTech Connect

    Britton, C.L., Jr.; Brown, G.M.; Bryan, W.L.; Clonts, L.G.; DePriest, J.C.; Emergy, M.S.; Ericson, M.N.; Hu, Z.; Jones, R.L.; Moore, M.R.; Oden, P.I.; Rochelle, J.M.; Smith, S.F.; Threatt, T.D.; Thundat, T.; Turner, G.W.; Warmack, R.J.; Wintenberg, A.L.

    1999-03-11

    A surface-micromachined MEMS process has been used to demonstrate multiple-input chemical sensing using selectively coated cantilever arrays. Combined hydrogen and mercury-vapor detection was achieved with a palm-sized, self-powered module with spread-spectrum telemetry reporting.

  1. Design of Barker coded multiple pulse experiments

    NASA Astrophysics Data System (ADS)

    Zamlutti, C. J.

    1980-12-01

    The combination of Barker-coded pulse compression techniques with the multiple pulse technique in incoherent scatter studies of the lower ionosphere is discussed. The basic principles of both techniques are reviewed, and the combined technique is presented as consisting of the coding of each pulse of the multiple pulse scheme by a b-baud Barker code. Design considerations for measurements from which the autocorrelation function can be computed are examined for the case of the radar at Arecibo, and possible experiments for observations of sporadic E layers, man-made ionospheric modification and the nighttime E layer are proposed. It is noted that the advantage of the Barker-coded multiple pulse technique consists in the possibility of obtaining simultaneously height and frequency resolution, which is important in the observation of thin layers with narrow frequency spectra.

  2. Application of neutron multiplicity counting to waste assay

    SciTech Connect

    Pickrell, M.M.; Ensslin, N.; Sharpe, T.J.

    1997-11-01

    This paper describes the use of a new figure of merit code that calculates both bias and precision for coincidence and multiplicity counting, and determines the optimum regions for each in waste assay applications. A {open_quotes}tunable multiplicity{close_quotes} approach is developed that uses a combination of coincidence and multiplicity counting to minimize the total assay error. An example is shown where multiplicity analysis is used to solve for mass, alpha, and multiplication and tunable multiplicity is shown to work well. The approach provides a method for selecting coincidence, multiplicity, or tunable multiplicity counting to give the best assay with the lowest total error over a broad spectrum of assay conditions. 9 refs., 6 figs.

  3. [Psychoneuroimmunology and multiple sclerosis].

    PubMed

    Mel'nikov, M V; Pashchenkov, M V; Boĭko, A N

    2015-01-01

    In this review, the authors discuss interactions between mental, nervous and immune systems in multiple sclerosis, an impact of psycho-emotional stress on disease development and progression as well as possible mechanisms of these interactions.

  4. Multiple shell fusion targets

    DOEpatents

    Lindl, J.D.; Bangerter, R.O.

    1975-10-31

    Multiple shell fusion targets for use with electron beam and ion beam implosion systems are described. The multiple shell targets are of the low-power type and use a separate relatively low Z, low density ablator at large radius for the outer shell, which reduces the focusing and power requirements of the implosion system while maintaining reasonable aspect ratios. The targets use a high Z, high density pusher shell placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. For example, with ion beams as a power source, breakeven at 10-20 Terrawatts with 10 MeV alpha particles for imploding a multiple shell target can be accomplished.

  5. The Multiplicative Situation

    ERIC Educational Resources Information Center

    Hurst, Chris

    2015-01-01

    The relationships between three critical elements, and the associated mathematical language, to assist students to make the critical transition from additive to multiplicative thinking are examined in this article by Chris Hurst.

  6. Multiple beam ptychography

    NASA Astrophysics Data System (ADS)

    Karl, Robert; Bevis, Charles; Lopez-Rios, Raymond; Reichanadter, Jonathan; Gardner, Dennis F.; Porter, Christina; Shanblatt, Elisabeth; Tanksalvala, Michael; Mancini, Giulia F.; Murnane, Margaret; Kapteyn, Henry; Adams, Daniel

    2016-03-01

    We present an extension to ptychography that allows simultaneous deconvolution of multiple, spatially separate, illuminating probes. This enables an increased field of view and hence, an increase in imaging throughput, without increased exposure times. This technique can be used for any non-interfering probes: demonstrated with multiple wavelengths and orthogonal polarizations. The latter of which gives us spatially resolved polarization spectroscopy from a single scan.

  7. Mobile multiple access study

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Multiple access techniques (FDMA, CDMA, TDMA) for the mobile user and attempts to identify the current best technique are discussed. Traffic loading is considered as well as voice and data modulation and spacecraft and system design. Emphasis is placed on developing mobile terminal cost estimates for the selected design. In addition, design examples are presented for the alternative techniques of multiple access in order to compare with the selected technique.

  8. Trousseau's syndrome: multiple definitions and multiple mechanisms

    PubMed Central

    2007-01-01

    In 1865, Armand Trousseau noted that unexpected or migratory thrombophlebitis could be a forewarning of an occult visceral malignancy. An analysis by Sack and colleagues in 1977 extended the term Trousseau's syndrome to include chronic disseminated intravascular coagulopathy associated with microangiopathy, verrucous endocarditis, and arterial emboli in patients with cancer, often occurring with mucin-positive carcinomas. In recent times the term has been ascribed to various clinical situations, ranging all the way from these classic descriptions to any kind of coagulopathy occurring in the setting of any kind of malignancy. These multiple definitions of Trousseau's syndrome are partly the consequence of multiple pathophysiologic mechanisms that apparently contribute to the hypercoagulability associated with cancer. Even the classic syndrome probably represents a spectrum of disorders, ranging from exaggerated fluid-phased thrombosis dependent on prothrombotic agents such as tissue factor to a platelet- and endotheliumum-based selectin-dependent microangiopathy associated with mucin-producing carcinomas, along with thrombin and fibrin production. Also considered here are recent hypotheses about genetic pathways within tumor cells that might trigger these thrombotic phenomena, and the reasons why therapy with heparins of various kinds remain the preferred treatment, probably because of their salutary actions on several of the proposed pathologic mechanisms. PMID:17496204

  9. Multiple Indicators, Multiple Causes Measurement Error Models

    PubMed Central

    Tekwe, Carmen D.; Carter, Randy L.; Cullings, Harry M.; Carroll, Raymond J.

    2014-01-01

    Multiple Indicators, Multiple Causes Models (MIMIC) are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times however when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this paper are: (1) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model, (2) to develop likelihood based estimation methods for the MIMIC ME model, (3) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. As a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure. PMID:24962535

  10. Multiple indicators, multiple causes measurement error models.

    PubMed

    Tekwe, Carmen D; Carter, Randy L; Cullings, Harry M; Carroll, Raymond J

    2014-11-10

    Multiple indicators, multiple causes (MIMIC) models are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times, however, when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this paper are as follows: (i) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model; (ii) to develop likelihood-based estimation methods for the MIMIC ME model; and (iii) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. As a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure. PMID:24962535

  11. Diverse array-designed modes of combination therapies in Fangjiomics.

    PubMed

    Liu, Jun; Wang, Zhong

    2015-06-01

    In line with the complexity of disease networks, diverse combination therapies have been demonstrated potential in the treatment of different patients with complex diseases in a personal combination profile. However, the identification of rational, compatible and effective drug combinations remains an ongoing challenge. Based on a holistic theory integrated with reductionism, Fangjiomics systematically develops multiple modes of array-designed combination therapies. We define diverse "magic shotgun" vertical, horizontal, focusing, siege and dynamic arrays according to different spatiotemporal distributions of hits on targets, pathways and networks. Through these multiple adaptive modes for treating complex diseases, Fangjiomics may help to identify rational drug combinations with synergistic or additive efficacy but reduced adverse side effects that reverse complex diseases by reconstructing or rewiring multiple targets, pathways and networks. Such a novel paradigm for combination therapies may allow us to achieve more precise treatments by developing phenotype-driven quantitative multi-scale modeling for rational drug combinations. PMID:25864646

  12. Immunological treatment of multiple sclerosis.

    PubMed

    Diebold, Martin; Derfuss, Tobias

    2016-04-01

    Treatment of multiple sclerosis (MS) has been a challenge since its first description by Charcot. The advent of immunomodulatory drugs in the mid 1990s brought the first big change in the treatment of MS patients. During the last 10 years there has been an ongoing tremendous evolution of novel treatment options for relapsing-remitting MS. These options include monoclonal antibodies, which inhibit migration of lymphocytes (natalizumab), deplete lymphocytes (alemtuzumab), or block the cytokine receptor interleukin (IL)-2 (daclizumab), teriflunomide that inhibits proliferation of activated lymphocytes, fingolimod that modulates the sphingosine-receptor system, and dimethylfumarate that combines features of immunomodulatory and immunosuppressive drugs. The topic of this review is to discuss currently available treatments and provide an outlook into the near future. PMID:27312167

  13. The Influence of Group Membership on Multiple Substance Use.

    ERIC Educational Resources Information Center

    Elder, Craig; Barnes, Jeremy; Leaver-Dunn, Deidre; Nagy, Steven; Leeper, James

    2001-01-01

    Study assessed the influence of group membership on the use of multiple substances among adolescents. Organized group activity included clubs and organizations, as well as athletic participation. Multiple substance included current use of any combination of alcohol, tobacco, and marijuana. Group participation had a buffering effect on multiple…

  14. Multiple sclerosis and human T-cell lymphotropic retroviruses

    NASA Astrophysics Data System (ADS)

    Koprowski, Hilary; Defreitas, Elaine C.; Harper, Mary E.; Sandberg-Wollheim, Magnhild; Sheremata, William A.; Robert-Guroff, Marjorie; Saxinger, Carl W.; Feinberg, Mark B.; Wong-Staal, Flossie; Gallo, Robert C.

    1985-11-01

    A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

  15. The More the Merrier? Multiple Parent-Adult Child Relations

    ERIC Educational Resources Information Center

    Ward, Russell A.; Spitze, Glenna; Deane, Glenn

    2009-01-01

    Although parent-adult child ties are generally positive, most parents have multiple children whose relations may yield collective ambivalence combining higher and lower quality. Little research has investigated these multiple relations. NSFH respondents aged 50+ with adult children (N = 2,270) are used to assess patterns of quality and contact…

  16. Multiple Query Evaluation Based on an Enhanced Genetic Algorithm.

    ERIC Educational Resources Information Center

    Tamine, Lynda; Chrisment, Claude; Boughanem, Mohand

    2003-01-01

    Explains the use of genetic algorithms to combine results from multiple query evaluations to improve relevance in information retrieval. Discusses niching techniques, relevance feedback techniques, and evolution heuristics, and compares retrieval results obtained by both genetic multiple query evaluation and classical single query evaluation…

  17. Simultaneous Two-Way Clustering of Multiple Correspondence Analysis

    ERIC Educational Resources Information Center

    Hwang, Heungsun; Dillon, William R.

    2010-01-01

    A 2-way clustering approach to multiple correspondence analysis is proposed to account for cluster-level heterogeneity of both respondents and variable categories in multivariate categorical data. Specifically, in the proposed method, multiple correspondence analysis is combined with k-means in a unified framework in which "k"-means is applied…

  18. Neuromaturation of multiples.

    PubMed

    Allen, Marilee C; Donohue, Pamela K

    2002-06-01

    Etiology of preterm birth and degree of maturation are the primary determinants of a preterm infant's survival and complications. Multiple gestation increases the likelihood of preterm birth but its influence on rate of maturation or complications of prematurity has been controversial, primarily because of confounding variables (e.g. race, aetiology of preterm delivery, degree of prematurity and pregnancy complications). Very low birthweight preterm multiples have virtually the same rates of neonatal mortality, complications and neuromaturation as preterm singletons of the same gestational age. There is no advantage of delivering twins or higher order multiples before 30 weeks gestation, unless a fetus decompensates in utero. Survival improves for near term intermediate-size preterm multiples while intrauterine growth decelerates and placental and fetal neuromaturation accelerate. These data and the high fetal death rate at term support delivery of multiples as soon as there is fetal lung maturity, and consideration of elective delivery of twins at 35-38 weeks gestation and triplets at 33-35 weeks gestation.

  19. Automatic cytometric device using multiple wavelength excitations

    NASA Astrophysics Data System (ADS)

    Rongeat, Nelly; Ledroit, Sylvain; Chauvet, Laurence; Cremien, Didier; Urankar, Alexandra; Couderc, Vincent; Nérin, Philippe

    2011-05-01

    Precise identification of eosinophils, basophils, and specific subpopulations of blood cells (B lymphocytes) in an unconventional automatic hematology analyzer is demonstrated. Our specific apparatus mixes two excitation radiations by means of an acousto-optics tunable filter to properly control fluorescence emission of phycoerythrin cyanin 5 (PC5) conjugated to antibodies (anti-CD20 or anti-CRTH2) and Thiazole Orange. This way our analyzer combining techniques of hematology analysis and flow cytometry based on multiple fluorescence detection, drastically improves the signal to noise ratio and decreases the spectral overlaps impact coming from multiple fluorescence emissions.

  20. Genetics Home Reference: multiple sclerosis

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions multiple sclerosis multiple sclerosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Multiple sclerosis is a condition characterized by areas of damage ( ...