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Sample records for combined multiple intraluminal

  1. Esophageal solid bolus transit: studies using combined multichannel intraluminal impedance and manometry in healthy volunteers.

    PubMed

    Chen, C L; Yi, C H; Chou, A S B; Liu, T T

    2013-01-01

    The purpose of this study is to apply combined multichannel intraluminal impedance and esophageal manometry (MII-EM) to test esophageal function during solid swallowing in a normal healthy population. We determined whether combined MII-EM with solid bolus is more sensitive than that with viscous bolus in the detection of motility abnormality. Eighteen healthy volunteers (11 men and 7 women; mean age 22 years, range 20-26 years) underwent combined MII-EM with a catheter containing four impedance-measuring segments and five solid-state pressure transducers. Each subject received 10 viscous and 10 solid materials. Tracings were analyzed manually for bolus presence time, total bolus transit time, contraction amplitude, duration, and onset velocity. Three hundred and sixty swallows including viscous and solid materials were analyzed. Contraction amplitude for the viscous swallows was higher at 20 cm above the lower esophageal sphincter (LES) (P= 0.049) but lower at 15 cm above the LES (P < 0.001). Duration of contractions for the solid swallows was longer at 15 cm (P= 0.002) and 10 cm above the LES (P= 0.011) compared with viscous swallows. The total bolus transit time for solid was significantly shorter than that for viscous boluses (6.8 vs. 7.7 seconds, P < 0.001). Bolus presence time appeared to be similar between viscous and solid boluses (except in the proximal esophagus). The percentage of swallows with ineffective peristalsis by manometry, as well as those with incomplete bolus transit by impedance, did not differ between viscous and solid swallows. The proportion of manometrically ineffective solid swallows with incomplete bolus transit was greater than that of viscous swallows (62.1% vs. 34.8%, P= 0.05). Application of solid boluses may potentially enhance diagnostic capability of esophageal function testing. Solid boluses can be regarded as a valuable complement to viscous boluses in the detection of esophageal motility abnormalities when applied with

  2. Usefulness of Intraluminal Brachytherapy Combined With External Beam Radiation Therapy for Submucosal Esophageal Cancer: Long-Term Follow-Up Results

    SciTech Connect

    Ishikawa, Hitoshi; Nonaka, Tetsuo; Sakurai, Hideyuki; Tamaki, Yoshio; Kitamoto, Yoshizumi; Ebara, Takeshi; Shioya, Mariko; Noda, Shin-Ei; Shirai, Katsuyuki; Suzuki, Yoshiyuki; Takahashi, Takeo; Nakano, Takashi

    2010-02-01

    Purpose: To assess the efficacy of radiation therapy (RT) by using intraluminal brachytherapy (IBT) combined with external beam RT (EBRT) for submucosal esophageal cancer. Methods and Materials: Between 1991 and 2005, 59 consecutive patients received definitive RT without chemotherapy. IBT was performed after patients completed EBRT as a booster therapy for 17 patients, using low-dose-rate Cs-137 sources until 1997, and for 19 patients, using high-dose-rate Ir-192 sources thereafter. The long-term outcomes were investigated with a median follow-up time of 61 months. Results: Logoregional recurrences and distant metastases were observed in 14 patients and in 2 patients in the lung, respectively, and 5 patients were rescued by salvage treatments. The 5-year logoregional control and cause-specific survival rates were 75% and 76%, respectively. The 5-year cause-specific survival rate in the EBRT group was 62%, whereas the corresponding rate in the IBT group was 86% (p = 0.04). Multivariate analysis revealed that IBT was the most powerful predictor of survival but did not reach a significant level (p = 0.07). There were five esophageal ulcers in the IBT group, but no ulcers developed with small fractions of 3 Gy. Grade 2 or higher cardiorespiratory complications developed in 2 patients (5.6%) in the IBT group and in 3 patients (13.0%) in the EBRT group. Conclusions: Combining IBT with EBRT is suggested to be one of the preferable treatment modalities for medically inoperable submucosal esophageal cancer because of its preferable local control and survival probabilities, with appreciably less morbidity.

  3. Evaluation of Gastroesophageal Reflux by Combined Multichannel Intraluminal Impedance and pH Monitoring and Esophageal Motility Patterns in Children with Esophageal Atresia.

    PubMed

    Tong, Stanley; Mallitt, Kylie-Ann; Krishnan, Usha

    2016-08-01

    Background Gastroesophageal reflux disease (GERD) and esophageal dysmotility are common in patients with esophageal atresia (EA). The aim of this study was to evaluate GERD and esophageal motility patterns in children with EA using combined multichannel intraluminal impedance and pH (MII-pH) monitoring and high-resolution esophageal manometry (HREM), respectively. The reflux patterns seen in EA patients were also compared with a control group of normal children with suspected GERD. Methods A retrospective chart review was done on 35 patients with EA and 35 age- and sex-matched normal controls with suspected GERD, who had undergone 24-hour MII-pH monitoring. Impedance data were compared between both cohorts. Eight of the EA patients also underwent HREM. Results In the EA cohort, the median age was 53 months, with 21 males, and 71.4% had Type C EA. A total of 85.7% of the EA cohort and 40% of the control group were on proton-pump inhibitor (PPI) therapy during the MII-pH study. There was no significant difference in the total retrograde bolus movements (RBMs) between the EA cohort (1,457) and the control group (1,482). Acidic RBMs was significantly lower in the EA group (208) compared with the control group (689), p = 0.0008. Nonacid reflux index (NARI) was significantly higher in EA children (1.1; 0.0-7.8) compared with controls (0.6; 0.0-5.7), p = 0.0046. In EA patients, only 335/1,183 (28%) total symptom occurrences were associated with RBM. The mean distal baseline impedance (DBI) was significantly lower in EA (1,029.6 [410.9 SD] Ω) compared with controls (2,998.2 [1028.8 SD] Ω) with suspected GERD, p < 0.0001. By logistic regression, only PPI use had a significant effect on DBI, p < 0.0001. HREM was abnormal in all eight EA patients. Four out of eight EA patients had a different peristaltic pattern for their solid swallows compared with their liquid swallows in HREM. Conclusions MII-pH testing allowed increased detection of nonacid

  4. Large intraluminal ileal hematoma presenting as small bowel obstruction in a child.

    PubMed

    Lim, Yun Jung; Nam, So Hyun; Kim, Seon Jeong

    2015-04-01

    Intraluminal small bowel hematoma has been rarely reported in children, as a rare cause of small bowel obstruction. We present a case of an intraluminal ileal hematoma presenting as small bowel obstruction in a child. Computed Tomography (CT) indicated a large intraluminal hyperdense lesion in the distal ileum as the cause of small bowel obstruction. Abdominal ultrasonography (US) showed an echogenic mass-like lesion with multiple septa in the distal ileum. Small bowel obstruction due to a complicated cystic mass was provisionally diagnosed. Histopathologic examination of the resected mass suggested a submucosal ileal hematoma. Although intraluminal small bowel hematoma is rare in children, it can present as an intraluminal cystic mass and should be considered as a rare cause of small bowel obstruction. The US and CT findings of submucosal ileal hematoma could be useful for the diagnosis of such cases in the future.

  5. 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.

  6. Intraluminal Drug Delivery to the Mouse Arteriovenous Fistula Endothelium

    PubMed Central

    Hashimoto, Takuya; Yamamoto, Kota; Foster, Trenton; Bai, Hualong; Shigematsu, Kunihiro; Dardik, Alan

    2016-01-01

    Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The simple murine AVF model was combined with intraluminal administration of drug solution to the venous endothelium at the same time as fistula creation. Technical aspects of this model are discussed. Under general anesthesia, an abdominal incision is made and the aorta and inferior vena cava (IVC) are exposed. The infra-renal aorta and IVC are dissected for clamping. After proximal and distal clamping, the puncture site is exposed and a 25 G needle is used to puncture both walls of the aorta and into the IVC. Immediately after the puncture, a reporter gene-expressing viral vector was infused in the IVC via the same needle, followed by 15 min of incubation. The intraluminal administration method enabled more robust viral gene delivery to the venous endothelium compared to administration by the external route. This novel method of delivery will facilitate studies that explore the role of the endothelium in AVF maturation and enable intraluminal drug delivery at the time of surgical operation. PMID:26967580

  7. 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.

  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. 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...

  10. 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...

  11. 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...

  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. 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.

  15. Combining multiple features for color texture classification

    NASA Astrophysics Data System (ADS)

    Cusano, Claudio; Napoletano, Paolo; Schettini, Raimondo

    2016-11-01

    The analysis of color and texture has a long history in image analysis and computer vision. These two properties are often considered as independent, even though they are strongly related in images of natural objects and materials. Correlation between color and texture information is especially relevant in the case of variable illumination, a condition that has a crucial impact on the effectiveness of most visual descriptors. We propose an ensemble of hand-crafted image descriptors designed to capture different aspects of color textures. We show that the use of these descriptors in a multiple classifiers framework makes it possible to achieve a very high classification accuracy in classifying texture images acquired under different lighting conditions. A powerful alternative to hand-crafted descriptors is represented by features obtained with deep learning methods. We also show how the proposed combining strategy hand-crafted and convolutional neural networks features can be used together to further improve the classification accuracy. Experimental results on a food database (raw food texture) demonstrate the effectiveness of the proposed strategy.

  16. In lower extremity PTAs intraluminal is better than subintimal.

    PubMed

    Bosiers, M; Deloose, K; Callaert, J; Maene, L; Keirse, K; Verbist, J; Peeters, P

    2012-04-01

    With subintimal recanalization, a channel is deliberately created by dissecting the vessel wall in order to replace the native occluded lumen. This is opposed to intraluminal recanalization, where passage of an arterial obstructive lesion is performed by central luminal navigation. Both intraluminal and subintimal treatment has its proponents and adversaries. The appreciation of an investigator for a certain technique is commonly related to the training received and the personal experience. Yet, the intraluminal technique uses the clinically preferred route for adjunctive treatment, such as balloon angioplasty or stent deployment. A wide variety of devices designed to obtain intraluminal lesion passage is available and is currently being used in vascular centers worldwide. With intraluminal techniques, success rates of up to 95% have been reported.

  17. 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.

  18. Long-term survival after intraluminal brachytherapy for inoperable hilar cholangiocarcinoma: A case report

    PubMed Central

    Chan, Siu-Yin; Poon, Ronnie T.; Ng, Kelvin K.; Liu, Chi-Leung; Chan, Raymond T.; Fan, Sheung-Tat

    2005-01-01

    Surgical resection with a tumor-free margin is the only curative treatment for hilar cholangiocarcinoma (Klatskin tumor). However, over half of the patients present late with unresectable tumors. Radiotherapy using external beam irradiation or intraluminal brachytherapy (ILBT) has been used to treat unresectable hilar cholangiocarcinoma with satisfactory outcome. We reported a patient with unresectable hilar cholangiocarcinoma surviving more than 6 years after combined external beam irradiation and ILBT. PMID:15918211

  19. [Treatment of atherosclerosis. New percutaneous intraluminal techniques].

    PubMed

    Lablanche, J M

    1990-10-06

    Balloon-catheter angioplasty was introduced by Gruntzig in 1977 and has since proved effective, but 3 problems are still encountered: immediate reobstruction, restenosis during the first 3 months and extension of the procedure to a greater number of cases. In an attempt to solve these problems, other percutaneous/technics, associated or not with balloon angioplasty, have been devised. They are: (1) intraluminal stents which perfectly keep the vessel open after balloon angioplasty; (2) vaporization of atheromatous plaques by laser, and notably excimer laser which results in immediate recanalization, later completed by balloon angioplasty; (3) heating balloons which stick dissections and improve the immediate success rate; (4) atheroma-cutting and storing systems, such as Simpson's atherocath, cutting and aspirating systems, such as Stack's transluminal extraction catheter, or erasing systems, such as Auth's rotablator; (5) other sources of energy, such as ultrasounds, microwaves and radiofrequencies, will perhaps, be used in the near future. None of these new technics has solved the restenosis problem, but all have proved effective in suppressing the obstacle, there by giving hopes of reducing immediate complications and gradually widening the indications of percutaneous revascularization.

  20. Intraluminal radiation therapy in the management of malignant biliary obstruction

    SciTech Connect

    Molt, P.; Hopfan, S.; Watson, R.C.; Botet, J.F.; Brennan, M.F.

    1986-02-01

    Fifteen patients with malignant biliary obstruction from carcinoma of the bile ducts, gallbladder, and pancreas (Group I) or metastatic disease (Group II) were treated with intraluminal radiation therapy (ILRT) at Memorial Sloan-Kettering Cancer Center. In 11 cases ILRT was used as a central boost in combination with 3000 cGy external beam radiation therapy (ERT). No significant treatment toxicity was observed. Cholangiographic response was observed in 2 of 12 evaluable patients. In no patient was long-term relief of jaundice without indwelling biliary stent achieved. Survival from treatment in eight Group I patients treated with ILRT +/- ERT was 3 to 13 months (median, 4.5). Survival in seven similarly treated Group II patients was 0.5 to 8 months (median, 4.0). Additional data for ten similar patients referred for ILRT but treated with ERT alone are presented. Analysis of this and other reports indicate the need for prospective controlled trials of the role of this regimen in the management of malignant biliary obstruction before wider application can be recommended.

  1. Procedure for the semi-automatic detection of gastro-oesophageal reflux patterns in intraluminal impedance measurements in infants.

    PubMed

    Trachterna, M; Wenzl, T G; Silny, J; Rau, G; Heimann, G

    1999-04-01

    The diagnosis of gastro-oesophageal reflux (GOR) is of great interest for paediatric gastroenterologists. pH monitoring is the commonly used procedure for GOR diagnosis but a major amount of postprandial GOR is missed due to the mostly non-acidic gastric contents in infants. The multiple intraluminal impedance technique is based on the recording of the impedance changes during bolus transport inside the oesophagus. It is the first method which allows the pH-independent, long-term registration of GOR. The use of the impedance technology in clinical practice has been limited so far by the time-consuming, visual evaluation of the impedance traces. The new approach of a semi-automatic analysis of the impedance measurements allows the automated detection of reflux patterns. It is based on event marking and an optimised feature description of the impedance traces combined with a fuzzy system for pattern recognition. The classifier is developed and tested on 50 investigations in infants. Compared to the comprehensive, multiple visual evaluation the achieved precision is 75% sensitivity and 48% positive prediction. In comparison to a single visual evaluation the analysis of the automatically proposed patterns corresponds to a 96% reduction of the evaluation time with no loss of precision. Thus the applicability of the impedance technology is enhanced significantly. A combined measurement of pH and impedance gives evidence about the occurrence of GOR, its pH and the acidic exposure of the oesophagus.

  2. Intraluminal crawling versus interstitial neutrophil migration during inflammation.

    PubMed

    Pick, Robert; Brechtefeld, Doris; Walzog, Barbara

    2013-08-01

    Site-directed trafficking of polymorphonuclear neutrophils (PMN) to their target regions within the tissue is an important prerequisite for efficient host defense during the acute inflammatory response. This process requires intraluminal crawling of PMN on the activated endothelial cells to their extravasation sites. Upon transendothelial diapedesis, PMN migrate in the interstitial tissue to sites of inflammation. These crucial steps within the recruitment cascade are defined as intraluminal crawling and interstitial migration. In this review, we will focus on the molecular mechanisms that control and fine-tune these migratory processes and discuss the role of adhesion molecules of the β2 integrin (CD11/CD18) family for these cellular functions.

  3. Carfilzomib boosted combination therapy for relapsed multiple myeloma

    PubMed Central

    Steiner, Raphael E; Manasanch, Elisabet E

    2017-01-01

    Carfilzomib is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome, the proteolytic core particle within the 26S proteasome, resulting in the accumulation of proteasome substrates and ultimately growth arrest and apoptosis of tumor cells. The development and ultimate approval of this medication by regulatory agencies has been an important step toward improving clinical outcomes in multiple myeloma. Although initially approved as a single agent for the treatment of multiply relapsed and/or refractory myeloma, in the USA, it is now widely used in the early relapse setting in combination with lenalidomide and dexamethasone. Carfilzomib has also been studied in combination with second-generation immunomodulatory drugs, histone deacetylase inhibitors, alkylating agents and other novel medications. In this review article, we will discuss the efficacy, safety, tolerability and quality of life of carfilzomib-based combination therapies, as well as novel agents, for relapsed multiple myeloma. PMID:28243125

  4. Carfilzomib boosted combination therapy for relapsed multiple myeloma.

    PubMed

    Steiner, Raphael E; Manasanch, Elisabet E

    2017-01-01

    Carfilzomib is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome, the proteolytic core particle within the 26S proteasome, resulting in the accumulation of proteasome substrates and ultimately growth arrest and apoptosis of tumor cells. The development and ultimate approval of this medication by regulatory agencies has been an important step toward improving clinical outcomes in multiple myeloma. Although initially approved as a single agent for the treatment of multiply relapsed and/or refractory myeloma, in the USA, it is now widely used in the early relapse setting in combination with lenalidomide and dexamethasone. Carfilzomib has also been studied in combination with second-generation immunomodulatory drugs, histone deacetylase inhibitors, alkylating agents and other novel medications. In this review article, we will discuss the efficacy, safety, tolerability and quality of life of carfilzomib-based combination therapies, as well as novel agents, for relapsed multiple myeloma.

  5. Gossypiboma: An Unusual Presentation as Perforation and Intraluminal Migration

    PubMed Central

    Mahey, Rajesh Kumar; Patil, Rajesh; Bakale, Nilesh; Suryawanshi, Sachin

    2016-01-01

    Gossypiboma is a mass formed around cotton material acting as foreign body in visceral cavity. In our study, we present a case of gossypiboma following open cholecystectomy. A surgical sponge left in the peritoneal cavity following cholecystectomy, caused inflammatory reaction, perforation and intraluminal migration. It is a relatively rare presentation. This patient underwent emergency laparotomy with Billroth II anastomosis and sponge removal. PMID:27790511

  6. A pedunculated intraluminal foregut reduplication cyst of the proximal esophagus.

    PubMed

    Craig, S R; Wallace, W H; Scott, D J; Cameron, E W

    1998-06-01

    A 66-year-old woman with a 3-month history of progressive dysphagia underwent transoral excision of a pedunculated cyst arising in the proximal esophagus. Histologic examination confirmed a pedunculated intraluminal foregut reduplication cyst. She remains well 1 year after excision with no recurrence of dysphagia.

  7. Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma.

    PubMed

    Hoy, Sheridan M

    2016-04-01

    Carfilzomib (Kyprolis®) is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome (the proteolytic core particle within the 26S proteasome), inducing growth arrest and apoptosis. This intravenous drug is approved in the EU and the USA as combination therapy with oral lenalidomide and intravenous or oral dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. In the multinational, phase III ASPIRE study in this patient population, carfilzomib triple combination therapy significantly prolonged progression-free survival (PFS), reflecting a clinically relevant gain in PFS of 8.7 months, compared with lenalidomide plus dexamethasone. Improvements in overall response rate and patients' global health status were also observed with carfilzomib triple combination therapy. A significant improvement in overall survival (OS) is yet to be demonstrated, with the prespecified stopping boundary not crossed at the time of the prespecified interim analysis, although OS data were not mature by the cut-off date. Carfilzomib triple combination therapy had a manageable tolerability profile. The incidences of the most frequently reported grade 3 or higher adverse events of special interest (with the exception of neutropenia, anaemia and thrombocytopenia) were low in both the carfilzomib triple combination therapy and lenalidomide plus dexamethasone groups. Although final OS data are awaited, current evidence suggests carfilzomib in combination with lenalidomide and dexamethasone is a welcome addition to the treatment options currently available for patients with relapsed multiple myeloma.

  8. Combining Results of Multiple Search Engines in Proteomics*

    PubMed Central

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

    2013-01-01

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

  9. 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.

  10. 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

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

    PubMed

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

    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.

  12. 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

  13. Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol

    SciTech Connect

    Miller, M.J.; Zhang, x.J.; Gu, x.A.; Clark, D.A. )

    1991-07-01

    Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of {sup 51}Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in {sup 51}Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal {sup 51}Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol.

  14. Combining Results From Multiple Evaluations of the Same Measurand

    PubMed Central

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

    2011-01-01

    According to the Guide to the Expression of Uncertainty in Measurement (GUM), a result of measurement consists of a measured value together with its associated standard uncertainty. The measured value and the standard uncertainty are interpreted as the expected value and the standard deviation of a state-of-knowledge probability distribution attributed to the measurand. We discuss the term metrological compatibility introduced by the International Vocabulary of Metrology, third edition (VIM3) for lack of significant differences between two or more results of measurement for the same measurand. Sometimes a combined result of measurement from multiple evaluations of the same measurand is needed. We propose an approach for determining a combined result which is metrologically compatible with the contributing results. PMID:26989601

  15. Combining multiple anatomical MRI measures improves Alzheimer's disease classification.

    PubMed

    de Vos, Frank; Schouten, Tijn M; Hafkemeijer, Anne; Dopper, Elise G P; van Swieten, John C; de Rooij, Mark; van der Grond, Jeroen; Rombouts, Serge A R B

    2016-05-01

    Several anatomical MRI markers for Alzheimer's disease (AD) have been identified. Hippocampal volume, cortical thickness, and grey matter density have been used successfully to discriminate AD patients from controls. These anatomical MRI measures have so far mainly been used separately. The full potential of anatomical MRI scans for AD diagnosis might thus not yet have been used optimally. In this study, we therefore combined multiple anatomical MRI measures to improve diagnostic classification of AD. For 21 clinically diagnosed AD patients and 21 cognitively normal controls, we calculated (i) cortical thickness, (ii) cortical area, (iii) cortical curvature, (iv) grey matter density, (v) subcortical volumes, and (vi) hippocampal shape. These six measures were used separately and combined as predictors in an elastic net logistic regression. We made receiver operating curve plots and calculated the area under the curve (AUC) to determine classification performance. AUC values for the single measures ranged from 0.67 (cortical thickness) to 0.94 (grey matter density). The combination of all six measures resulted in an AUC of 0.98. Our results demonstrate that the different anatomical MRI measures contain complementary information. A combination of these measures may therefore improve accuracy of AD diagnosis in clinical practice. Hum Brain Mapp 37:1920-1929, 2016. © 2016 Wiley Periodicals, Inc.

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

    PubMed Central

    Fraundorf, Scott H.; Benjamin, Aaron S.

    2013-01-01

    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. PMID:24511178

  17. 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.

  18. 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.

  19. Oral contraceptives combined with interferon β in multiple sclerosis

    PubMed Central

    De Giglio, Laura; Barletta, Valeria T.; Marinelli, Fabiana; Angelis, Floriana De; Gallo, Valentina; Pagano, Veronica A.; Marini, Stefano; Piattella, Maria C.; Tomassini, Valentina; Pantano, Patrizia

    2015-01-01

    Objective: To test the effect of oral contraceptives (OCs) in combination with interferon β (IFN-β) on disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: One hundred fifty women with RRMS were randomized in a 1:1:1 ratio to receive IFN-β-1a subcutaneously (SC) only (group 1), IFN-β-1a SC plus ethinylstradiol 20 μg and desogestrel 150 μg (group 2), or IFN-β-1a SC plus ethinylestradiol 40 μg and desogestrel 125 μg (group 3). The primary endpoint was the cumulative number of combined unique active (CUA) lesions on brain MRI at week 96. Secondary endpoints included MRI and clinical and safety measures. Results: The estimated number of cumulative CUA lesions at week 96 was 0.98 (95% confidence interval [CI] 0.81–1.14) in group 1, 0.84 (95% CI 0.66–1.02) in group 2, and 0.72 (95% CI 0.53–0.91) in group 3, with a decrease of 14.1% (p = 0.24) and 26.5% (p = 0.04) when comparing group 1 with groups 2 and 3, respectively. The number of patients with no gadolinium-enhancing lesions was greater in group 3 than in group 1 (p = 0.03). No significant differences were detected in other secondary endpoints. IFN-β or OC discontinuations were equally distributed across groups. Conclusions: Our results translate the observations derived from experimental models to patients, supporting the anti-inflammatory effects of OCs with high-dose estrogens, and suggest possible directions for future research. Classification of evidence: This study provides Class II evidence that in women with RRMS, IFN-β plus ethinylstradiol and desogestrel decreases the cumulative number of active brain MRI lesions compared with IFN-β alone. PMID:26140279

  20. 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.

  1. 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.

  2. Exploiting strength, discounting weakness: combining information from multiple climate simulators.

    PubMed

    Chandler, Richard E

    2013-05-28

    This paper presents and analyses a statistical framework for combining projections of future climate from different climate simulators. The framework recognizes explicitly that all currently available simulators are imperfect; that they do not span the full range of possible decisions on the part of the climate modelling community; and that individual simulators have strengths and weaknesses. Information from individual simulators is automatically weighted, alongside that from historical observations and from prior knowledge. The weights for a simulator depend on its internal variability, its expected consensus with other simulators, the internal variability of the real climate and the propensity of simulators collectively to deviate from reality. The framework demonstrates, moreover, that some subjective judgements are inevitable when interpreting multiple climate change projections: by clarifying precisely what those judgements are, it provides increased transparency in the ensuing analyses. Although the framework is straightforward to apply in practice by a user with some understanding of Bayesian methods, the emphasis here is on conceptual aspects illustrated with a simplified artificial example. A 'poor man's version' is also presented, which can be implemented straightforwardly in simple situations.

  3. Intraluminal bubble dynamics induced by lithotripsy shock wave

    NASA Astrophysics Data System (ADS)

    Song, Jie; Bai, Jiaming; Zhou, Yufeng

    2016-12-01

    Extracorporeal shock wave lithotripsy (ESWL) has been the first option in the treatment of calculi in the upper urinary tract since its introduction. ESWL-induced renal injury is also found after treatment and is assumed to associate with intraluminal bubble dynamics. To further understand the interaction of bubble expansion and collapse with the vessel wall, the finite element method (FEM) was used to simulate intraluminal bubble dynamics and calculate the distribution of stress in the vessel wall and surrounding soft tissue during cavitation. The effects of peak pressure, vessel size, and stiffness of soft tissue were investigated. Significant dilation on the vessel wall occurs after contacting with rapid and large bubble expansion, and then vessel deformation propagates in the axial direction. During bubble collapse, large shear stress is found to be applied to the vessel wall at a clinical lithotripter setting (i.e. 40 MPa peak pressure), which may be the mechanism of ESWL-induced vessel rupture. The decrease of vessel size and viscosity of soft tissue would enhance vessel deformation and, consequently, increase the generated shear stress and normal stresses. Meanwhile, a significantly asymmetric bubble boundary is also found due to faster axial bubble expansion and shrinkage than in radial direction, and deformation of the vessel wall may result in the formation of microjets in the axial direction. Therefore, this numerical work would illustrate the mechanism of ESWL-induced tissue injury in order to develop appropriate counteractive strategies for reduced adverse effects.

  4. Combined interpretation of multiple geophysical techniques: an archaeological case study

    NASA Astrophysics Data System (ADS)

    Riedl, S.; Reichmann, S.; Tronicke, J.; Lück, E.

    2009-04-01

    In order to locate and ascertain the dimensions of an ancient orangery, we explored an area of about 70 m x 60 m in the Rheinsberg Palace Garden (Germany) with multiple geophysical techniques. The Rheinsberg Park, situated about 100 km northwest of Berlin, Germany, was established by the Prussian emperors in the 18th century. Due to redesign of the architecture and the landscaping during the past 300 years, buildings were dismantled and detailed knowledge about some original buildings got lost. We surveyed an area close to a gazebo where, after historical sources, an orangery was planned around the year 1740. However, today it is not clear to what extent this plan has been realized and if remains of this building are still buried in the subsurface. Applied geophysical techniques include magnetic gradiometry, frequency domain electromagnetic (FDEM) and direct current (DC) resistivity mapping as well as ground penetrating radar (GPR). To get an overview of the site, we performed FDEM electrical conductivity mapping using an EM38 instrument and magnetic gradiometry with caesium magnetometers. Both data sets were collected with an in- and crossline data point spacing of ca. 10 cm and 50 cm, respectively. DC resistivity surveying was performed using a pole-pole electrode configuration with an electrode spacing of 1.5 m and a spacing of 1.0 m between individual readings. A 3-D GPR survey was conducted using 200 MHz antennae and in- and crossline spacing of ca. 10 cm and 40 cm, respectively. A standard processing sequence including 3-D migration was applied. A combined interpretation of all collected data sets illustrates that the magnetic gradient and the EM38 conductivity maps is are dominated by anomalies from metallic water pipes from belonging to the irrigation system of the park. The DC resistivity map outlines a rectangular area which might indicate the extension of a former building south of the gazebo. The 3-D GPR data set provides further insights about

  5. HDR intraluminal brachytherapy for lung tumours--a case report.

    PubMed

    Wee, J T; Yang, E T; Lim, Y C

    1994-06-01

    The lung is a common site for cancer to occur, for both primary as well as metastases. The presence of such tumours can give rise to symptoms such as haemoptysis, cough, breathlessness and pneumonia. In most cases, treatment is strictly for palliation. We present a case report of a patient with an endobronchial metastasis from a primary hypernephroma which recurred following external beam radiotherapy. He was treated with a single fraction of intraluminal brachytherapy to a dose of 10Gy at 1 cm from the axis on a High Dose Rate Ir192 Remote Afterloading Machine. There were no adverse effects following treatment. On follow-up 7 months later, the patient did not have any further recurrence of breathlessness although his disease had progressed at other sites.

  6. 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.

  7. 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.

  8. Changes in intraluminal pressure in rat large intestines with aging and effects of dietary fiber.

    PubMed

    Murakami, H; Iwane, S; Munakata, A; Nakaji, S; Sugawara, K; Tsuchida, S; Sasaki, D

    2001-06-01

    Changes in intraluminal pressure in rat colon with aging and with the effects of dietary fiber were measured. A pressure sensor was inserted into the rat large intestine under endoscopic guidance. The intraluminal pressure curve in the colon was recorded, and the motility index was calculated by this curve. The rats were divided into three groups with a fiber-free diet, a cellulose diet (10% w/w), or a pectin diet (10% w/w). Intraluminal pressure was measured in the proximal, middle, and distal colon at 2, 4, 8, 12, and 16 months after birth. Intraluminal pressure in three sites increased with age and decreased in the latter half of the study. The motility index was lower during the course in the fiber groups, especially the pectin group more than the nonfiber group. This result suggests that long-term ingestion of dietary fiber might have a prophylactic effect on the development of diverticula.

  9. 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.

  10. 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…

  11. [Experimental and clinical study of an intraluminal sutureless prosthesis].

    PubMed

    Maruyama, Y

    1989-10-01

    An intraluminal sutureless prosthesis is now used for vascular reconstruction of dissecting aneurysms and atherosclerotic aortic aneurysms. Although excellent results have been reported from ligature have been very little studied. An experimental study of the sutureless prosthesis in dogs and our clinical experience with 15 cases are reported in this article. Twenty-three mongrel dogs were anesthetized and their left pleural cavity was entered through the third or fourth intercostal space. A stainless steel tube covered with low porosity woven Dacron graft, both internally and externally, was inserted into the descending aorta and tied into place tightly with suture materials. After 73 to 542 days (average 154 days) the aorta, including the tube, was removed and the aortic wall was examined histologically. A tensile strength test was also performed with 10 dogs. Severe histological changes, that is, complete disruption of elastic fibers of media, or partial exposure of the ligature inside the aorta, was found in 19 of 37 examined portions (51.3%). In the tensile strength test on the ligated area, the maximal load which ruptured the specimen was within 100 +/- 10% of the values for the control aortic wall in three dogs, 111% or more in three dogs and 89% or less in four dogs. The elongation was less than 100% in all dogs. No relationship was apparent between the time elapsed since operation, the severity of histologic change and maximal tension. During the period from February, 1979 to November, 1984, eleven men and four women, whose average age was 60, underwent aortic reconstructions using an intraluminal sutureless prosthesis at our center. Ten patients had dissecting aneurysms and 5 had atherosclerotic thoracic aneurysms. The mean operating time and mean bleeding volume was 8 hours 18 minutes and 2,513 ml, respectively. Five patients died in hospital. Three, with type I dissections died of bleeding, cerebral damage and renal failure. Two, with atherosclerotic

  12. [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.

  13. Attenuation characterization of multiple combinations of imperfect polarizers.

    PubMed

    Huang, Chong; Zhao, Shuang; Chen, Haiqing; Liao, Zhaoshu

    2010-05-01

    Malus's law, when used to calculate the attenuation ratio of the combination of two imperfect polarizers (two-CIP), will introduce an error, especially near the crossed-axis orientation. In this paper, first, the Jones matrix of the imperfect polarizer is deduced and an exact algorithm of the attenuation ratio of the two-CIP is proposed as well as its monotonic attenuation interval. Experimental results confirm that our deduced expression is more accurate than Malus's law. Then based on this algorithm, an attenuation-ratio expression of the combination of three imperfect polarizers (three-CIP) is presented. In this three-CIP model, it is found that when the electric field amplitude ratio of the imperfect polarizer is epsilon, the attenuation ratio can change from 1 to epsilon(4) monotonically in a general model when P(1) and P(3) are rotated and P(2) is fixed, which is proved by experiment. Finally, it is deduced that the combination of n imperfect polarizers (n-CIP) can obtain a minimum attenuation ratio of epsilon(2(n-1)), which indicates the number of imperfect polarizers needed to achieve the required attenuation ratio.

  14. 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.

  15. Cytogenetic monoclonality in multifocal uroepithelial carcinomas: evidence of intraluminal tumour seeding

    PubMed Central

    Fadl-Elmula, I; Gorunova, L; Mandahl, N; Elfving, P; Lundgren, R; Mitelman, F; Heim, S

    1999-01-01

    Twenty-one multifocal urinary tract transitional cell carcinomas, mostly bladder tumours, from a total of six patients were processed for cytogenetic analysis after short-term culturing of the tumour cells. Karyotypically related, often identical, cytogenetically complex clones were found in all informative tumours from each case, including the recurrent tumours. Rearrangement of chromosome 9, leading to loss of material from the short and/or the long arm, was seen in all cases, indicating that this is an early, pathogenetically important event in transitional cell carcinogenesis. The presence of related clones with great karyotypic similarity in anatomically distinct tumours from the same bladder indicates that multifocal uroepithelial tumours have a monoclonal origin and arise via intraluminal seeding of viable cancer cells shed from the original tumour. Later lesions may develop also from cells shed from the so called second primary tumours. The relatively complex karyotypes seen in all lesions from most cases argue that the seeding of tumour cells is a late event that succeeds the acquisition by them of multiple secondary genetic abnormalities. © 1999 Cancer Research Campaign PMID:10487605

  16. 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

  17. A combination assay for simultaneous assessment of multiple signaling pathways.

    PubMed

    Goetz, A S; Liacos, J; Yingling, J; Ignar, D M

    1999-12-01

    We have developed an assay in which modulation of two or more signaling pathways can be assessed concurrently by combining reporter gene systems with fluorescent probe technology. The validation of this method was achieved by indirect analysis of adenylyl cyclase activation with the use of a cyclic AMP response element (CRE)-luciferase reporter system in combination with the measurement of calcium mobilization by Calcium Green-1 AM fluorescence on a fluorescent imaging plate reader. To demonstrate the utility of the method in studying the pharmacology of receptors that couple to more than one G protein, Chinese hamster ovary (CHO) cells, which stably expressed both the CRE-luciferase reporter gene and the human pituitary adenylyl cyclase-activating peptide (PACAP) receptor, were treated with PACAP 1-27 and 1-38. Calcium mobilization and the induction of adenylyl cyclase activity in response to each concentration of peptide were assessed in individuals wells. This assay may also be used to screen for ligands of two or more unrelated receptors simultaneously without compromising the assessment of either signaling pathway. To illustrate this point, Rat-1 fibroblasts, which expressed human alpha1A receptors, were cocultured with CRE-luciferase CHO cells, which expressed human GLP-1 receptors. Calcium mobilization elicited by phenylephrine agonism of the alpha1A receptor was assessed in the same assay as GLP-1-induced activation of adenylyl cyclase. The pEC(50) for each agonist was similar to that observed when the cell lines were not cocultured. The number of different receptors that can be screened per well is limited only by the ability to distinguish different reporter gene signals and fluorescent indicators.

  18. 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…

  19. Multiplicity fluctuation and correlation of identified baryons in a quark combination model

    NASA Astrophysics Data System (ADS)

    Song, Jun; Li, Hai-hong; Wang, Rui-qin; Shao, Feng-lan

    2017-01-01

    The dynamical multiplicity fluctuations and correlations of identified baryons and antibaryons produced by the hadronization of a bulk quark system are systematically studied in a quark combination model. Starting from the most basic dynamics of the quark combination which is necessary for multiplicity study, we analyze moments (variance, skewness, and kurtosis) of inclusive multiplicity distributions of identified baryons, two-baryon multiplicity correlations, and baryon-antibaryon multiplicity correlations after the hadronization of a quark system with given quark number and antiquark number. We obtain a series of interesting results, e.g., binomial behavior of multiplicity moments, coinciding flavor-dependent two-baryon correlation, and universal baryon-antibaryon correlation, which can be regarded as general features of the quark combination. We further take into account correlations and fluctuations of quark numbers before hadronization and study their influence on multiple production of baryons and antibaryons. We find that quark number fluctuations and flavor conservation lead to a series of important results such as the negative p Ω¯ + multiplicity correlation and universal two-baryon correlations. We also study the influence of resonance decays in order to compare our results with future experimental data in ultrarelativistic heavy ion collisions at the Large Hadron Collider.

  20. Intraluminal and intracavitary vacuum therapy for esophageal leakage: a new endoscopic minimally invasive approach.

    PubMed

    Loske, G; Schorsch, T; Müller, C

    2011-06-01

    Endoscopic treatment by placement of a vacuum sponge drainage system is a new option in the management of leakages in the digestive tract. We now distinguish between two treatment variants: the intracavitary and intraluminal techniques. A drainage system comprising an appropriately trimmed polyurethane foam sponge and a gastric-type tube is either placed through the esophageal defect into an extraluminal wound cavity (intracavitary method), or directly onto the defect with the sponge remaining within the esophageal lumen (intraluminal method). Continuous negative pressure of 125 mmHg is then applied, resulting in stabilizing of the sponge and continuous drainage and sealing of the defect. We report a case series of 14 patients, presenting the full range of possible esophageal defects that were successfully treated with either intracavitary or intraluminal vacuum therapy. Complete healing of the esophageal defect was achieved in 13 patients; one patient died due to fulminant pseudomembranous colitis while the esophageal defect was nearly healed.

  1. Multiple-Symbol combined differential detection for satellite-based AIS Signals

    NASA Astrophysics Data System (ADS)

    Hao, Jingsong; Ma, Shexiang; Wang, Junfeng; Meng, Xin

    2015-12-01

    In this paper, a multiple-symbol combined differential Viterbi decoding algorithm which is insensitive to frequency offset is proposed. According to the theories of multiple-symbol differential detection and maximum-likelihood detection, we combine the multiple-order differential information with the Viterbi algorithm. The phase shift caused by the frequency offset is estimated and compensated from the above information in the process of decoding. The simulation results show that the bit error rate (BER) of 2 bits combined differential Viterbi algorithm is below 10-3 when the normalized signal-to-noise ratio (NSNR) is 11 dB, and the decoding performances approach those of the coherent detection as the length of the combined differential symbols increases. The proposed method is simple and its performance remains stable under different frequency offsets.

  2. 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.

  3. Entrainment of intestinal slow waves with electrical stimulation using intraluminal electrodes.

    PubMed

    Lin, X; Hayes, J; Peters, L J; Chen, J D

    2000-05-01

    The aim of this study was to investigate whether the intestinal stimulation would be feasible using a less invasive method: intraluminal electrodes. The study was performed in nine healthy hound dogs (15-26 kg). Four pairs of electrodes were implanted on the serosa of the jejunum at an interval of 5 cm with the most proximal pair 35 cm beyond the pylorus. An intestinal fistula was made 20 cm beyond the pylorus. Simultaneous recordings of intestinal myoelectrical activity were made for 2 h in the fasting state from both intraluminal and serosal electrodes. Various pacing parameters were tested. The frequency of the intestinal slow wave recorded from the intraluminal electrodes was identical to that from the serosal electrodes (18.78+/-0.3 cpm vs 18.75+/-0.3 cpm, r=0.99, p <0.001), and so was the percentage of normal 17-22 cycles/ min waves (95.83+/-3.9% vs 98.16+/-1.33%, r=0.96, p<0.01). A complete entrainment of the intestinal slow wave was achieved in every dog with electrical stimulation using intraluminal ring electrodes. The effective pacing parameters were pulse width of 70 ms, amplitude of 4 mA and frequency of 1.1 IF (intrinsic frequency). The time required for the entrainment of the intestinal slow wave with intraluminal pacing was 25.0+/-2.1 s. The maximum driven frequency was found to be 1.43+/-0.01 IF. The results reveal that intraluminal pacing is an effective and efficient method for the entrainment of intestinal slow waves. It may become a potential approach for the treatment of intestinal motor disorders associated with myoelectrical abnormalities.

  4. Esophageal Bolus Transit in Newborns with Gastroesophageal Reflux Disease Symptoms: A Multichannel Intraluminal Impedance Study

    PubMed Central

    Liguori, Stefania Alfonsina; Maggiora, Elena; Locatelli, Emanuela; Indrio, Flavia; Bertino, Enrico; Coscia, Alessandra

    2015-01-01

    Purpose The aim of this study was to evaluate bolus transit during esophageal swallow (ES) and gastroesophageal reflux (GER) events and to investigate the relationship between the characteristics of ES and GER events in a population of term and preterm newborns with symptoms of gastroesophageal reflux disease (GERD). Methods The study population consisted of term and preterm newborns referred to combined multichannel intraluminal impedance (MII) and pH monitoring for GERD symptoms. The frequency and characteristics of ES and GER events were assessed by two independent investigators. Statistical significance was set at p<0.05. Results Fifty-four newborns (23 preterm) were included in the analyses. Median bolus head advancing time corrected for esophageal length (BHATc) was shorter during mealtime than during the postprandial period (median, interquartile range): 0.20 (0.15-0.29) s/cm vs. 0.47 (0.39-0.64) s/cm, p<0.001. Median bolus presence time (BPT) was prolonged during mealtime: 4.71(3.49-6.27) s vs. 2.66 (1.82-3.73) s, p<0.001. Higher BHATc (p=0.03) and prolonged BPT (p<0.001) were observed in preterm newborns during the postprandial period. A significant positive correlation between BHATc and bolus clearance time was also observed (ρ=0.33, p=0.016). Conclusion The analysis of ES and GER events at the same time by MII provides useful information to better understand the physiopathology of GERD. In particular, the analysis of BHATc during the postprandial period could help clinicians identify newborns with prolonged esophageal clearance time due to impaired esophageal motility, which could allow for more accurate recommendations regarding further tests and treatment. PMID:26770898

  5. Site and characteristics of electrolyte loss and effect of intraluminal glucose in experimental canine cholera

    PubMed Central

    Carpenter, Charles C. J.; Sack, R. Bradley; Feeley, John C.; Steenberg, Richard W.

    1968-01-01

    The site and characteristics of gastrointestinal electrolyte loss were investigated in eight dogs with experimental cholera induced by orogastric administration of 6-hr broth cultures of Vibrio cholerae, strain Ogawa 395. In these animals, all electrolyte losses originated in the small bowel, predominantly from the jejunum and ileum. The bicarbonate concentration of the small bowel fluid showed a progressive increase from duodenum, where it was less than that of plasma, to the terminal ileum, where it was significantly greater than that of simultaneously obtained plasma. Studies of the responses of chronic Thiry-Vella jejunal loops (five dogs) and chronic Thiry-Vella ileal loops (five dogs) to intraluminal challenge by cholera exotoxin demonstrated that all loops exhibited isotonic electrolyte loss for a 14-18 hr period after challenge. The bicarbonate concentration of fluid produced by exotoxin-challenged jejunal loops was not significantly different from that of plasma, whereas the ileal loops produced fluid with a bicarbonate concentration approximately three times that of plasma. The effect of intraluminal glucose on the response of canine gut to cholera exotoxin was investigated by perfusion studies in 12 dogs with chronic Thiry-Vella fistulae. Intraluminal glucose significantly enhanced isotonic fluid absorption in both jejunal and ileal loops. The net effects of glucose on isotonic fluid absorption were equal before and after intraluminal administration of crude cholera exotoxin. These data suggest that cholera exotoxin causes gut electrolyte loss by a mechanism independent of that by which glucose enhances sodium absorption. Images PMID:5645863

  6. Magnetic retraction of bowel by intraluminal injectable cyanoacrylate-based magnetic glue.

    PubMed

    Wang, Zhigang; 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- μ Ps) 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.

  7. 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

  8. Acute gastric pH changes alter intraluminal but not plasma peptide levels.

    PubMed

    Mueller, C R; Ure, T; O'Dorisio, T M; Barrie, R J; Woltering, E A

    1991-12-01

    Gastric acidity is influenced by systemic and local peptide effects. Previous work by others has shown that intraluminally secreted peptides may have a role in local control of gastric acidity; however, the response of these peptides to acute changes in gastric pH is unknown. To determine the effects of acute changes in pH on systemic and intraluminal peptide levels, 14 normal volunteers underwent placement of a nasogastric tube after an overnight fast. Blood and gastric fluid were analyzed on a control day, 2 hours after completion of 24 hours of aluminum-magnesium antacid therapy and after 24 hours of H2 blockade. Plasma and acid-alcohol-extracted gastric peptide levels were measured with specific radioimmunoassays. Specimens were subdivided into two groups: 28 gastric fluid specimens with a pH less than 4 and 10 specimens with a pH greater than 4. In the patients with a pH greater than 4, the luminal peptides, motilin, neurotensin, pancreatic polypeptide, somatostatin, substance P, and gastrin, were decreased by 50% to 90% and gastrin-releasing peptide was decreased by 36% compared with specimens with a pH less than 4. Conversely, intraluminal vasoactive intestinal polypeptide and calcitonin levels were elevated by 60% and 27%, respectively, in the samples with a pH greater than 4. Intraluminal peptide concentrations are responsive to changes in intragastric pH; however, this response was not seen in plasma peptide levels.

  9. Intraluminal acid activates esophageal nodose C fibers after mast cell activation

    PubMed Central

    Zhang, Shizhong; Liu, Zhenyu; Heldsinger, Andrea; Owyang, Chung

    2013-01-01

    Acid reflux in the esophagus can induce esophageal painful sensations such as heartburn and noncardiac chest pain. The mechanisms underlying acid-induced esophageal nociception are not clearly understood. In our previous studies, we characterized esophageal vagal nociceptive afferents and defined their responses to noxious mechanical and chemical stimulation. In the present study, we aim to determine their responses to intraluminal acid infusion. Extracellular single-unit recordings were performed in nodose ganglion neurons with intact nerve endings in the esophagus using ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal intraluminal acid perfusion were compared in naive and ovalbumin (OVA)-challenged animals, followed by measurements of transepithelial electrical resistance (TEER) and the expression of tight junction proteins (zona occludens-1 and occludin). In naive guinea pigs, intraluminal infusion with either acid (pH = 2–3) or capsaicin did not evoke an action potential discharge in esophageal nodose C fibers. In OVA-sensitized animals, following esophageal mast cell activation by in vivo OVA inhalation, intraluminal acid infusion for about 20 min started to evoke action potential discharges. This effect is further confirmed by selective mast cell activation using in vitro tissue OVA challenge in esophageal-vagal preparations. OVA inhalation leads to decreased TEER and zona occludens-1 expression, suggesting an impaired esophageal epithelial barrier function after mast cell activation. These data for the first time provide direct evidence of intraluminal acid-induced activation of esophageal nociceptive C fibers and suggest that mast cell activation may make esophageal epithelium more permeable to acid, which subsequently may increase esophageal vagal nociceptive C fiber activation. PMID:24264049

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

    Despite new advances in multiple myeloma treatment and the consequent improvement in overall survival, most patients relapse or become refractory to treatment. This suggests that new molecules and combinations that may further inhibit important survival pathways for these tumor cells are needed. In this context, zalypsis is a novel compound, derived from marine organisms, with a powerful preclinical anti-myeloma effect based on the sensitivity of malignant plasma cells to DNA-damage induction; and it has already been tested in a phase I/II clinical trial in multiple myeloma. We hypothesized that the addition of this compound to the combination of bortezomib plus dexamethasone may improve efficacy with acceptable toxicity. The triple combination demonstrated strong synergy and higher efficacy compared with double combinations; not only in vitro, but also ex vivo and, especially, in in vivo experiments. The triple combination triggers cell death, mainly through a synergistic induction of DNA damage and a decrease in the nuclear localization of nuclear factor kappa B. Our findings support the clinical evaluation of this combination for relapsed and refractory myeloma patients. PMID:27540138

  12. 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

  13. Expression of multiple cbb3 cytochrome c oxidase isoforms by combinations of multiple isosubunits in Pseudomonas aeruginosa.

    PubMed

    Hirai, Takehiro; Osamura, Tatsuya; Ishii, Masaharu; Arai, Hiroyuki

    2016-10-24

    The ubiquitous opportunistic human pathogen Pseudomonas aeruginosa has five terminal oxidases for aerobic respiration and uses them under different growth conditions. Two of them are cbb3-type cytochrome c oxidases encoded by the gene clusters ccoN1O1Q1P1 and ccoN2O2Q2P2, which are the main terminal oxidases under high- and low-oxygen conditions, respectively. P. aeruginosa also has two orphan gene clusters, ccoN3Q3 and ccoN4Q4, encoding the core catalytic CcoN isosubunits, but the roles of these genes have not been clarified. We found that 16 active cbb3 isoforms could be produced by combinations of four CcoN, two CcoO, and two CcoP isosubunits. The CcoN3- or CcoN4-containing isoforms were produced in the WT cell membrane in response to nitrite and cyanide, respectively. The strains carrying these isoforms were more resistant to nitrite or cyanide under low-oxygen conditions. These results indicate that P. aeruginosa gains resistance to respiratory inhibitors using multiple cbb3 isoforms with different features, which are produced through exchanges of multiple core catalytic isosubunits.

  14. 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.

  15. A combined neutron and gamma-ray multiplicity counter based on liquid scintillation detectors

    NASA Astrophysics Data System (ADS)

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

    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 ( γ) 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 compared with single-particle measurements. We present measurement results of n, γ, nn, nγ, γγ, nnn, nnγ, nγγ and γγγ 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 are discussed. Successful measurements of multiple rates can be performed also when using high-Z shielding.

  16. 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.

  17. 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

  18. Low-profile Visualized Intraluminal Support Junior Device for the Treatment of Intracranial Aneurysms

    PubMed Central

    Gupta, Mihir; Cheung, Vincent J; Abraham, Peter; Wali, Arvin R; Gabel, Brandon C; Almansouri, Abdulrahman; Pannell, J. Scott; Khalessi, Alexander A

    2017-01-01

    Objective: Early case series suggest that the recently introduced Low-profile Visualized Intraluminal Support Junior (LVIS Jr.) device (MicroVention-Terumo, Inc., Tustin, CA) may be used to treat wide-necked aneurysms that would otherwise require treatment with intrasaccular devices or open surgery. We report our single-center experience utilizing LVIS Jr. to treat intracranial aneurysms involving 1.8-2.5 mm parent arteries. Methods: We retrospectively reviewed records of patients treated with the LVIS Jr. device for intracranial aneurysms at a single center. A total of 21 aneurysms were treated in 18 patients. Aneurysms were 2-25 mm in diameter; one was ruptured, while three had recurred after previous rupture and treatment. Lesions were distributed across the anterior (n=12) and posterior (n=9) circulations. Three were fusiform morphology. Results: Stent deployment was successful in 100% of cases with no immediate complications. Seventeen aneurysms were treated with stent-assisted coil embolization resulting in immediate complete occlusion in 94% of cases. Two fusiform aneurysms arising from the posterior circulation were further treated with elective clip ligation after delayed expansion and recurrence; no lesions required further endovascular treatment. Four aneurysms were treated by flow diversion with stand-alone LVIS Jr. stent, and complete occlusion was achieved in three cases. Small foci of delayed ischemic injury were noted in two patients in the setting of antiplatelet medication noncompliance. No in-stent stenosis, migration, hemorrhage, or permanent deficits were observed. Good functional outcome based on the modified Rankin Scale score (mRS ≤ 2) was achieved in 100% of cases. Conclusion: Our midterm results suggest that the LVIS Jr. stent may be used for a variety of intracranial aneurysms involving small parent arteries (1.8-2.5 mm) with complete angiographic occlusion, parent vessel preservation, and functional clinical outcomes. This off

  19. Combination regimens using doxorubicin and pegylated liposomal doxorubicin prior to autologous transplantation in multiple myeloma.

    PubMed

    Moreau, Philippe

    2009-07-01

    Doxorubicin and pegylated liposomal doxorubicin are key compounds of several induction regimens used prior to autologous stem cell transplantation in patients with de novo multiple myeloma, such as vincristine, doxorubicin, dexamethasone (VAD), vincristine, pegylated liposomal doxorubicin/Doxil, dexamethasone (DVd) or PS-341/bortezomib, doxorubicin, dexamethasone (PAD). The aim of this article is to summarize the more recent data available on the efficacy of these combinations and to discuss their role as part of initial therapy.

  20. 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.

  1. Pegylated liposomal doxorubicin and immunomodulatory drug combinations in multiple myeloma: rationale and clinical experience.

    PubMed

    Chanan-Khan, Asher Alban; Lee, Kelvin

    2007-04-01

    The availability of new agents for multiple myeloma (MM) provides an opportunity to further improve response rates through the development of new combination regimens. Such new agents include pegylated liposomal doxorubicin (PLD) and the immunomodulatory drugs thalidomide and lenalidomide, all of which have demonstrated efficacy and safety in the treatment of newly diagnosed and relapsed/refractory MM. Based on their complementary mechanisms of action and nonoverlapping toxicity profiles, PLD and the immunomodulatory drugs might provide incremental benefits when used in combined treatment regimens. Thus, they have been evaluated in clinical studies that combine PLD/vincristine/dexamethasone and thalidomide (DVd-T) or PLD/vincristine/dexamethasone and lenalidomide (DVd-R) as well as in a study combining bortezomib with PLD and thalidomide. Results of all these studies have included high overall response rates, with improved rates of complete/near complete response compared with similar regimens that do not include chemotherapy (ie, immunomodulatory drugs plus dexamethasone). This article provides the clinical rationale for the use of PLD in combination with immunomodulatory drugs to treat patients with MM and summarizes the clinical experience with these combinations to date. Notably, the early phase I/II study results have been sufficiently encouraging to warrant further investigation in additional large-scale, phase II/III studies. Future clinical trials should focus on determining the optimal dose and schedule for each of these agents when used in combination and whether the addition of other new agents provides an additional response benefit.

  2. Relationships between motor patterns and intraluminal pressure in the 3-taeniated proximal colon of the rabbit

    PubMed Central

    Quan, Xiaojing; Yang, Zixian; Xue, Mai; Chen, Ji-Hong; Huizinga, Jan D.

    2017-01-01

    Manometry is used worldwide to assess motor function of the gastrointestinal tract, and the measured intraluminal pressure patterns are usually equated with contraction patterns. In the colon, simultaneous pressure increases throughout the entire colon are most often called simultaneous contractions, although this inference has never been verified. To evaluate the relationship between pressure and contraction in the colon we performed high-resolution manometry and measured diameter changes reflecting circular muscle contractions in the rabbit colon. We show that within a certain range of contraction amplitudes and frequencies, the intraluminal pressure pattern faithfully resembles the contraction pattern. However, when the frequency is very high (as in fast propagating contractions in a cluster) the consequent intraluminal pressures merge. When the contraction speed of propagation is very fast (above ~5 cm/s), the resulting pressure occurs simultaneous throughout the colon; hence simultaneous pressure is measured as are caused by fast propagating contractions. The very slow propagating, low amplitude haustral boundary contractions show a very characteristic pattern in spatiotemporal contraction maps that is not faithfully reproduced in the pressure maps. Correct interpretation of pressure events in high-resolution manometry is essential to make it a reliable tool for diagnosis and management of patients with colon motor dysfunction. PMID:28195136

  3. 'It's all foreign to me': how to decipher gastrointestinal intraluminal foreign bodies.

    PubMed

    Shaish, Hiram; Gilet, Anthony; Gerard, Perry

    2015-10-01

    In evaluating the gastrointestinal tract, whether in the emergency room setting, the inpatient setting or the outpatient setting, the radiologist may encounter a myriad of intraluminal radio-opaque, non-anatomic entities. It is the radiologist's role to distinguish between true foreign bodies and medical paraphernalia. Further, the later must be evaluated for proper positioning vs. improper, potentially detrimental positioning. While many foreign bodies from the community may be distinctly familiar to the radiologist, the large variety of medical tools in existence may not be. Furthermore, many medical devices are designed to transiently traverse, or interact with the gastrointestinal tract, requiring the radiologist to become familiar with their natural history. We explore a select group of common and uncommon intraluminal foreign bodies and will divide them into medical paraphernalia that are properly positioned; medical paraphernalia that are in abnormal locations and miscellaneous foreign bodies from the community. For each medical tool, we will discuss its development and medical utility, natural history as it relates to the gastrointestinal tract, optimal positioning as assessed radiologically, malpositioning, and subsequent complications. A small selection of unusual foreign bodies from the community will be presented. Finally, a selection of medical conditions which produce symptoms due to acquired intraluminal objects will be reviewed.

  4. 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.

  5. Combined statistical analyses for long-term stability data with multiple storage conditions: a simulation study.

    PubMed

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

    2014-01-01

    Shelf-life estimation usually requires that at least three registration batches are tested for stability at multiple storage conditions. The shelf-life estimates are often obtained by linear regression analysis per storage condition, an approach implicitly suggested by ICH guideline Q1E. A linear regression analysis combining all data from multiple storage conditions was recently proposed in the literature when variances are homogeneous across storage conditions. The combined analysis is expected to perform better than the separate analysis per storage condition, since pooling data would lead to an improved estimate of the variation and higher numbers of degrees of freedom, but this is not evident for shelf-life estimation. Indeed, the two approaches treat the observed initial batch results, the intercepts in the model, and poolability of batches differently, which may eliminate or reduce the expected advantage of the combined approach with respect to the separate approach. Therefore, a simulation study was performed to compare the distribution of simulated shelf-life estimates on several characteristics between the two approaches and to quantify the difference in shelf-life estimates. In general, the combined statistical analysis does estimate the true shelf life more consistently and precisely than the analysis per storage condition, but it did not outperform the separate analysis in all circumstances.

  6. 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.

  7. The emerging role of carfilzomib combination therapy in the management of multiple myeloma.

    PubMed

    Moreau, Philippe

    2014-04-01

    Carfilzomib is a proteasome inhibitor that selectively and irreversibly binds to its target, resulting in sustained inhibition absent of off-target effects relative to bortezomib. Single-agent carfilzomib has produced robust and durable responses in clinical trials and it has been approved in the US for treating relapsed and refractory multiple myeloma (MM). Due to its favorable safety profile, carfilzomib is particularly suitable for use in combination strategies. Promising data have been reported from studies that investigated the use of carfilzomib in combination with immunomodulators, alkylating agents, glucocorticoids, histone deacetylase inhibitors and kinesin spindle protein inhibitors. Ongoing pivotal randomized Phase III studies are investigating the efficacy and safety of carfilzomib combinations in patients with relapsed MM and transplant ineligible patients.

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

    DTIC Science & Technology

    2014-09-01

    and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI PRINCIPAL INVESTIGATOR: Dr. Caterina Mainero...studies in multiple sclerosis (MS) suggested that cortical demyelinating lesions, which are hardly detected in vivo on conventional magnetic resonance...disease progression in many MS cases. 15. SUBJECT TERMS Multiple sclerosis ; cortex; cortical sulci; neuroinflammation; microglia; cortical

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

    PubMed Central

    Yoo, Yun Joo; Sun, Lei; Poirier, Julia G.; Paterson, Andrew D.

    2016-01-01

    ABSTRACT By jointly analyzing multiple variants within a gene, instead of one at a time, gene‐based multiple regression can improve power, robustness, and interpretation in genetic association analysis. We investigate multiple linear combination (MLC) test statistics for analysis of common variants under realistic trait models with linkage disequilibrium (LD) based on HapMap Asian haplotypes. MLC is a directional test that exploits LD structure in a gene to construct clusters of closely correlated variants recoded such that the majority of pairwise correlations are positive. It combines variant effects within the same cluster linearly, and aggregates cluster‐specific effects in a quadratic sum of squares and cross‐products, producing a test statistic with reduced degrees of freedom (df) equal to the number of clusters. By simulation studies of 1000 genes from across the genome, we demonstrate that MLC is a well‐powered and robust choice among existing methods across a broad range of gene structures. Compared to minimum P‐value, variance‐component, and principal‐component methods, the mean power of MLC is never much lower than that of other methods, and can be higher, particularly with multiple causal variants. Moreover, the variation in gene‐specific MLC test size and power across 1000 genes is less than that of other methods, suggesting it is a complementary approach for discovery in genome‐wide analysis. The cluster construction of the MLC test statistics helps reveal within‐gene LD structure, allowing interpretation of clustered variants as haplotypic effects, while multiple regression helps to distinguish direct and indirect associations. PMID:27885705

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Voting-based consensus clustering for combining multiple clusterings of chemical structures

    PubMed Central

    2012-01-01

    Background Although many consensus clustering methods have been successfully used for combining multiple classifiers in many areas such as machine learning, applied statistics, pattern recognition and bioinformatics, few consensus clustering methods have been applied for combining multiple clusterings of chemical structures. It is known that any individual clustering method will not always give the best results for all types of applications. So, in this paper, three voting and graph-based consensus clusterings were used for combining multiple clusterings of chemical structures to enhance the ability of separating biologically active molecules from inactive ones in each cluster. Results The cumulative voting-based aggregation algorithm (CVAA), cluster-based similarity partitioning algorithm (CSPA) and hyper-graph partitioning algorithm (HGPA) were examined. The F-measure and Quality Partition Index method (QPI) were used to evaluate the clusterings and the results were compared to the Ward’s clustering method. The MDL Drug Data Report (MDDR) dataset was used for experiments and was represented by two 2D fingerprints, ALOGP and ECFP_4. The performance of voting-based consensus clustering method outperformed the Ward’s method using F-measure and QPI method for both ALOGP and ECFP_4 fingerprints, while the graph-based consensus clustering methods outperformed the Ward’s method only for ALOGP using QPI. The Jaccard and Euclidean distance measures were the methods of choice to generate the ensembles, which give the highest values for both criteria. Conclusions The results of the experiments show that consensus clustering methods can improve the effectiveness of chemical structures clusterings. The cumulative voting-based aggregation algorithm (CVAA) was the method of choice among consensus clustering methods. PMID:23244782

  15. Early And Present Examples Of Intraluminal Ultrasonic Echography

    NASA Astrophysics Data System (ADS)

    Bom, Nicolaas; Ten Hoff, H.; Lancee, Charles T.; Gussenhoven, Elma J.; Serruys, Patrick W.; Slager, C. J.; Roelandt, J.

    1989-08-01

    Although one of the great merits of medical application of ultrasound is the non-invasive character of the technique, there are several examples in which an invasive or semi-invasive application can be useful. Probably due to then poor sensitivity of the piezoelectric crystals some very early invasive echo applications are based on tube-or catheter-mounted echo elements. Echo-endoscopy for the inspection of body cavities dates back to the fifties. Not much later investigators began to develop intra-esophageal probes for inspection of the heart and great vessels. Transesophageal echography has become very important in cardiology today. Intravascular echo imaging has gained much interest. Such a technique would be very helpful in the diagnosis of obstructive arterial disease and the evaluation of therapeutic intervention. This echo technique has been suggested for steering of catheter-based desobstruction methods. A few examples of combined echo and desobstruction techniques as reported in literature are mentioned. With high-frequency intravascular real-time imaging it is possible to observe detailed information on arterial wall, fibrotic proliferation and atherosclerotic plaque.

  16. Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma

    PubMed Central

    Hideshima, T; Cottini, F; Ohguchi, H; Jakubikova, J; Gorgun, G; Mimura, N; Tai, Y-T; Munshi, N C; Richardson, P G; Anderson, K C

    2015-01-01

    Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi) also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger significant MM cell growth inhibition by inhibiting or downregulating c-Myc. Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity, associated with downregulation of c-Myc. Unexpectedly, we observed that decreased levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len shows less efficacy than simultaneous treatment with this combination. Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs, together with Len induces synergistic MM cytotoxicity without alteration of CRBN expression. Our results showed that only modest class-I HDAC inhibition is able to induce synergistic MM cytotoxicity in combination with Len. These studies may provide the framework for utilizing HDACi in combination with Len to both avoid CRBN downregulation and enhance anti-MM activities. PMID:25978432

  17. a Modified Stochastic Neighbor Embedding for Combining Multiple Features for Remote Sensing Image Classification

    NASA Astrophysics Data System (ADS)

    Zhang, L.; Zhang, L.; Tao, D.; Huang, X.

    2012-07-01

    In remote sensing image interpretation, it is important to combine multiple features of a certain pixel in both spatial and spectral domains to improve the classification accuracy, such as spectral signature, morphological property, and shape feature. Therefore, it is essential to consider the complementary property of different features and combine them in order to obtain an accurate classification rate. In this paper, we introduce a multi-feature dimension reduction algorithm under a probabilistic framework, modified stochastic neighbor embedding (MSNE). For each feature, a probability distribution is constructed based on SNE, and then we alternatively solve SNE and learn the optimal combination coefficients for different features in optimization. Compared with conventional dimension reduction strategies, the suggested algorithm can considers spectral, morphological and shape features of a pixel to achieve a physically meaningful low-dimensional feature representation by automatically learn a combination coefficient for each feature adapted to its contribution to subsequent classification. In experimental section, classification results using hyperspectral remote sensing image (HSI) show that this modified stochastic neighbor embedding can effectively improve classification performance.

  18. Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma.

    PubMed

    Hideshima, T; Cottini, F; Ohguchi, H; Jakubikova, J; Gorgun, G; Mimura, N; Tai, Y-T; Munshi, N C; Richardson, P G; Anderson, K C

    2015-05-15

    Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi) also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger significant MM cell growth inhibition by inhibiting or downregulating c-Myc. Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity, associated with downregulation of c-Myc. Unexpectedly, we observed that decreased levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len shows less efficacy than simultaneous treatment with this combination. Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs, together with Len induces synergistic MM cytotoxicity without alteration of CRBN expression. Our results showed that only modest class-I HDAC inhibition is able to induce synergistic MM cytotoxicity in combination with Len. These studies may provide the framework for utilizing HDACi in combination with Len to both avoid CRBN downregulation and enhance anti-MM activities.

  19. Compound heterozygous mutations in TTC7A cause familial multiple intestinal atresias and severe combined immunodeficiency.

    PubMed

    Yang, W; Lee, P P W; Thong, M-K; Ramanujam, T M; Shanmugam, A; Koh, M-T; Chan, K-W; Ying, D; Wang, Y; Shen, J J; Yang, J; Lau, Y L

    2015-12-01

    Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency (MIA-SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations.

  20. Multiple allogeneic progenitors in combination function as a unit to support early transient hematopoiesis in transplantation

    PubMed Central

    Takahashi, Satoshi; Lai, Chen-Yi; Nojima, Masanori; Yamamoto, Ryo; Takeuchi, Yasuo; Higashihara, Masaaki; Nakauchi, Hiromitsu

    2016-01-01

    Cord blood (CB) is a valuable donor source in hematopoietic cell transplantation. However, the initial time to engraftment in CB transplantation (CBT) is often delayed because of low graft cell numbers. This limits the use of CB. To overcome this cell dose barrier, we modeled an insufficient dose CBT setting in lethally irradiated mice and then added hematopoietic stem/progenitor cells (HSCs/HPCs; HSPCs) derived from four mouse allogeneic strains. The mixture of HSPCs rescued recipients and significantly accelerated hematopoietic recovery. Including T cells from one strain favored single-donor chimerism through graft versus graft reactions, with early hematopoietic recovery unaffected. Furthermore, using clinically relevant procedures, we successfully isolated a mixture of CD34+ cells from multiple frozen CB units at one time regardless of HLA-type disparities. These CD34+ cells in combination proved transplantable into immunodeficient mice. This work provides proof of concept that when circumstances require support of hematopoiesis, combined multiple units of allogeneic HSPCs are capable of early hematopoietic reconstitution while allowing single-donor hematopoiesis by a principal graft. PMID:27503070

  1. Modelling bias in combining small area prevalence estimates from multiple surveys.

    PubMed

    Manzi, Giancarlo; Spiegelhalter, David J; Turner, Rebecca M; Flowers, Julian; Thompson, Simon G

    2011-01-01

    SUMMARY: Combining information from multiple surveys can improve the quality of small area estimates. Customary approaches, such as the multiple-frame and statistical matching methods, require individual level data, whereas in practice often only multiple aggregate estimates are available. Commercial surveys usually produce such estimates without clear description of the methodology that is used. In this context, bias modelling is crucial, and we propose a series of Bayesian hierarchical models which allow for additive biases. Some of these models can also be fitted in a classical context, by using a mixed effects framework. We apply these methods to obtain estimates of smoking prevalence in local authorities across the east of England from seven surveys. All the surveys provide smoking prevalence estimates and confidence intervals at the local authority level, but they vary by time, sample size and transparency of methodology. Our models adjust for the biases in commercial surveys but incorporate information from all the sources to provide more accurate and precise estimates.

  2. 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

  3. 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.

  4. 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.

  5. Dosimetric impact of an air passage on intraluminal brachytherapy for bronchus cancer

    PubMed Central

    Okamoto, Hiroyuki; Wakita, Akihisa; Nakamura, Satoshi; Nishioka, Shie; Aikawa, Ako; Kato, Toru; Abe, Yoshihisa; Kobayashi, Kazuma; Inaba, Koji; Murakami, Naoya; Itami, Jun

    2016-01-01

    The brachytherapy dose calculations used in treatment planning systems (TPSs) have conventionally been performed assuming homogeneous water. Using measurements and a Monte Carlo simulation, we evaluated the dosimetric impact of an air passage on brachytherapy for bronchus cancer. To obtain the geometrical characteristics of an air passage, we analyzed the anatomical information from CT images of patients who underwent intraluminal brachytherapy using a high-dose-rate 192Ir source (MicroSelectron V2r®, Nucletron). Using an ionization chamber, we developed a measurement system capable of measuring the peripheral dose with or without an air cavity surrounding the catheter. Air cavities of five different radii (0.3, 0.5, 0.75, 1.25 and 1.5 cm) were modeled by cylindrical tubes surrounding the catheter. A Monte Carlo code (GEANT4) was also used to evaluate the dosimetric impact of the air cavity. Compared with dose calculations in homogeneous water, the measurements and GEANT4 indicated a maximum overdose of 5–8% near the surface of the air cavity (with the maximum radius of 1.5 cm). Conversely, they indicated a minimum overdose of ~1% in the region 3–5 cm from the cavity surface for the smallest radius of 0.3 cm. The dosimetric impact depended on the size and the distance of the air passage, as well as the length of the treatment region. Based on dose calculations in water, the TPS for intraluminal brachytherapy for bronchus cancer had an unexpected overdose of 3–5% for a mean radius of 0.75 cm. This study indicates the need for improvement in dose calculation accuracy with respect to intraluminal brachytherapy for bronchus cancer. PMID:27605630

  6. Tracking neutrophil intraluminal crawling, transendothelial migration and chemotaxis in tissue by intravital video microscopy.

    PubMed

    Xu, Najia; Lei, Xi; Liu, Lixin

    2011-09-24

    The recruitment of circulating leukocytes from blood stream to the inflamed tissue is a crucial and complex process of inflammation(1,2). In the postcapillary venules of inflamed tissue, leukocytes initially tether and roll on the luminal surface of venular wall. Rolling leukocytes arrest on endothelium and undergo firm adhesion in response to chemokine or other chemoattractants on the venular surface. Many adherent leukocytes relocate from the initial site of adhesion to the junctional extravasation site in endothelium, a process termed intraluminal crawling(3). Following crawling, leukocytes move across endothelium (transmigration) and migrate in extravascular tissue toward the source of chemoattractant (chemotaxis)(4). Intravital microscopy is a powerful tool for visualizing leukocyte-endothelial cell interactions in vivo and revealing cellular and molecular mechanisms of leukocyte recruitment(2,5). In this report, we provide a comprehensive description of using brightfield intravital microscopy to visualize and determine the detailed processes of neutrophil recruitment in mouse cremaster muscle in response to the gradient of a neutrophil chemoattractant. To induce neutrophil recruitment, a small piece of agarose gel (~1-mm(3) size) containing neutrophil chemoattractant MIP-2 (CXCL2, a CXC chemokine) or WKYMVm (Trp-Lys-Tyr-Val-D-Met, a synthetic analog of bacterial peptide) is placed on the muscle tissue adjacent to the observed postcapillary venule. With time-lapsed video photography and computer software ImageJ, neutrophil intraluminal crawling on endothelium, neutrophil transendothelial migration and the migration and chemotaxis in tissue are visualized and tracked. This protocol allows reliable and quantitative analysis of many neutrophil recruitment parameters such as intraluminal crawling velocity, transmigration time, detachment time, migration velocity, chemotaxis velocity and chemotaxis index in tissue. We demonstrate that using this protocol, these

  7. 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

  8. 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.

  9. 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

  10. Development of adjustment functions to assess combined safety effects of multiple treatments on rural two-lane roadways.

    PubMed

    Park, Juneyoung; Abdel-Aty, Mohamed

    2015-02-01

    Numerous studies have attempted to evaluate the safety effectiveness of specific single treatment on roadways by estimating crash modification factors (CMFs). However, there is a need to also assess safety effects of multiple treatments since multiple treatments are usually simultaneously applied to roadways. Due to the lack of sufficient CMFs of multiple treatments, the Highway Safety Manual (HSM) provides combining method for multiple CMFs. However, it is cautioned in the HSM and related sources that combined safety effect of multiple CMFs may be over or under estimated. Moreover, the literature did not evaluate the accuracy of the combining method using CMFs obtained from the same study area. Thus, the main objectives of this research are: (1) to estimate CMFs and crash modification functions (CM Functions) for two single treatments (shoulder rumble strips, widening (1-9ft) shoulder width) and combination (installing shoulder rumble strips+widening shoulder width) using the observational before-after with empirical Bayes (EB) method and (2) to develop adjustment factors and functions to assess combined safety effects of multiple treatments based on the accuracy of the combined CMFs for multiple treatments estimated by the existing combining method. Data was collected for rural two-lane roadways in Florida and Florida-specific safety performance functions (SPFs) were estimated for different crash types and severities. The CM Functions and adjustment functions were developed using linear and nonlinear regression models. The results of before-after with EB method show that the two single treatments and combination are effective in reducing total and SVROR (single vehicle run-off roadway) crashes. The results indicate that the treatments were more safety effective for the roadway segments with narrower original shoulder width in the before period. It was found that although the CMFs for multiple treatments (i.e., combination of two single treatments) were generally

  11. 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

  12. 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

  13. 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.

  14. Dual inhibition of Mcl-1 by the combination of carfilzomib and TG02 in multiple myeloma.

    PubMed

    Ponder, Katelyn G; Matulis, Shannon M; Hitosugi, Sadae; Gupta, Vikas A; Sharp, Cathy; Burrows, Francis; Nooka, Ajay K; Kaufman, Jonathan L; Lonial, Sagar; Boise, Lawrence H

    2016-07-02

    Carfilzomib (Kyprolis®), a second generation proteasome inhibitor, is FDA approved for single-agent use among relapsed/refractory multiple myeloma (MM). To enhance the therapeutic efficacy of carfilzomib, we sought to combine carfilzomib with other novel agents. TG02, a multi-kinase inhibitor, targets JAK2 and CDK9. The rationale for co-treatment with carfilzomib and TG02 is that both independently target Mcl-1 and most myeloma cells are dependent on this anti-apoptotic protein for survival. We observed at least additive effects using the combination treatment in MM cell lines and patient samples. To determine how the bone marrow environment affects the efficacy of the combination we conducted co-culture experiments with Hs-5 stromal cells. We also examined the mechanism of increased apoptosis by determining the affect on expression of the Bcl-2 family of proteins. We found that carfilzomib increases NOXA mRNA expression, as expected, and TG02 treatment caused a decrease in Mcl-1 protein but not mRNA levels. Consistent with this possibility, we find silencing CDK9 does not change carfilzomib sensitivity in the same manner as addition of TG02. Since changes in Mcl-1 protein occur in the presence of a proteasome inhibitor we hypothesize that regulation of Mcl-1 translation is the most likely mechanism. Taken together our data suggest that dual inhibition of Mcl-1 via decreased expression and the induction of its antagonist NOXA by the combination of carfilzomib and TG02 is active in myeloma and warrants further testing preclinically and in clinical trials. Moreover, regulation of Mcl-1 by TG02 is more complex than initially appreciated.

  15. Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models.

    PubMed

    Takahashi, Tsutomu; Honma, Yoshio; Miyake, Takaaki; Adachi, Koji; Takami, Saki; Okada, Masahiro; Kumanomidou, Satoshi; Ikejiri, Fumiyoshi; Jo, Yumi; Onishi, Chie; Kawakami, Koshi; Moriyama, Ichiro; Inoue, Masaya; Tanaka, Junko; Suzumiya, Junji

    2015-04-01

    Multiple myeloma is a malignant proliferative disease of plasma cells in the bone marrow and remains largely incurable. Cotylenin A, a fusicoccane diterpene glycoside with a complex sugar moiety, was isolated as a plant-growth regulator. Cotylenin A has been shown to inhibit the growth of various cancer cells. Herein, we examined the anti-myeloma effects of cotylenin A using five human myeloma cell lines (RPMI-8226, KMS-11, KMS-26, KMS-12 PE and KMS-12 BM) and xenografts in immunodeficient mice. Cotylenin A and vincristine synergistically inhibited the growth and induced apoptosis in myeloma cells. While other microtubule-disturbing agents also showed co-operative effects with cotylenin A, other anticancer agents, such as doxorubicin, cisplatin, camptothecin, methotrexate, gemcitabine and 5-fluorouracil, did not show such co-operation with cotylenin A. These differences might be attributed to the effects on autophagic responses. Combined treatment with cotylenin A and vincristine induced autophagy (formation of LC3-II and degradation of p62 protein). However, doxorubicin did not enhance the autophagy induced by cotylenin A. A colony-forming assay indicated that the combined treatment with cotylenin A and vincristine more effectively suppressed the formation of large colonies, which have higher self-renewal activity than vincristine alone. Expression of pluripotency-associated transcription factor Sox2 mRNA in RPMI-8226 myeloma cells was significantly suppressed by treatment with cotylenin A. Combined treatment with cotylenin A and vincristine significantly inhibited the growth of KMS-26 myeloma cells as xenografts. Our results suggest that the combination of cotylenin A and vincristine may have therapeutic value. Recently, it was reported that cotylenin A modulates the 14-3-3 intracellular signaling pathway. The 14-3-3 proteins may be novel targets in treating myeloma. However, our study could not explain how the sensitization to vincristine is related to the

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

    PubMed

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

    2015-02-14

    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.

  17. Multiple site receptor modeling with a minimal spanning tree combined with a Kohonen neural network

    NASA Astrophysics Data System (ADS)

    Hopke, Philip K.

    1999-12-01

    A combination of two pattern recognition methods has been developed that allows the generation of geographical emission maps form multivariate environmental data. In such a projection into a visually interpretable subspace by a Kohonen Self-Organizing Feature Map, the topology of the higher dimensional variables space can be preserved, but parts of the information about the correct neighborhood among the sample vectors will be lost. This can partly be compensated for by an additional projection of Prim's Minimal Spanning Tree into the trained neural network. This new environmental receptor modeling technique has been adapted for multiple sampling sites. The behavior of the method has been studied using simulated data. Subsequently, the method has been applied to mapping data sets from the Southern California Air Quality Study. The projection of a 17 chemical variables measured at up to 8 sampling sites provided a 2D, visually interpretable, geometrically reasonable arrangement of air pollution source sin the South Coast Air Basin.

  18. Robust video communication by combining scalability and multiple description coding techniques

    NASA Astrophysics Data System (ADS)

    Wang, Huisheng; Ortega, Antonio

    2003-05-01

    Layered coding (LC) and multiple description coding (MDC) have been proposed as two different kinds of 'quality adaptation' schemes for video delivery over the current Internet or wireless networks. To combine the advantages of LC and MDC, we present a new approach -- Multiple Description Layered Coding (MDLC), to provide reliable video communication over a wider range of network scenarios and application requirements. MDLC improves LC in that it introduces redundancy in each layer so that the chance of receiving at least one description of base layer is greatly enhanced. Though LC and MDC are each good in limit cases (e.g., long end-to-end delay for LC vs. short delay for MDC), the proposed MDLC system can address intermediate cases as well. Same as a LC system with retransmission, the MDLC system can have a feedback channel to indicate which descriptions have been correctly received. Thus a low redundancy MDLC system can be implemented with our proposed runtime packet scheduling system based on the feedback information. The goal of our scheduling algorithm is to find a proper on-line packet scheduling policy to maximize the playback quality at the decoder. Previous work on scheduling algorithms has not considered multiple decoding choices due to the redundancy between data units, because of the increase in complexity involved in considering alternate decoding paths. In this paper, we introduce a new model of Directed Acyclic HyperGraph (DAHG) to represent the data dependencies among frames and layers, as well as the data correlation between descriptions. The impact of each data unit to others is represented by messages passing along the graph with updates based on new information received. Experimental results show that the proposed system provides more robust and efficient video communication for real-time applications over lossy packet networks.

  19. 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

  20. An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species.

    PubMed

    Oeste, Clara L; Pinar, Mario; Schink, Kay O; Martínez-Turrión, Javier; Stenmark, Harald; Peñalva, Miguel A; Pérez-Sala, Dolores

    2014-01-01

    The C-terminal ends of small GTPases contain hypervariable sequences which may be posttranslationally modified by defined lipid moieties. The diverse structural motifs generated direct proteins towards specific cellular membranes or organelles. However, knowledge on the factors that determine these selective associations is limited. Here we show, using advanced microscopy, that the isoprenylation and palmitoylation motif of human RhoB (-CINCCKVL) targets chimeric proteins to intraluminal vesicles of endolysosomes in human cells, displaying preferential co-localization with components of the late endocytic pathway. Moreover, this distribution is conserved in distant species, including cells from amphibians, insects and fungi. Blocking lipidic modifications results in accumulation of CINCCKVL chimeras in the cytosol, from where they can reach endolysosomes upon release of this block. Remarkably, CINCCKVL constructs are sorted to intraluminal vesicles in a cholesterol-dependent process. In the lower species, neither the C-terminal sequence of RhoB, nor the endosomal distribution of its homologs are conserved; in spite of this, CINCCKVL constructs also reach endolysosomes in Xenopus laevis and insect cells. Strikingly, this behavior is prominent in the filamentous ascomycete fungus Aspergillus nidulans, in which GFP-CINCCKVL is sorted into endosomes and vacuoles in a lipidation-dependent manner and allows monitoring endosomal movement in live fungi. In summary, the isoprenylated and palmitoylated CINCCKVL sequence constitutes a specific structure which delineates an endolysosomal sorting strategy operative in phylogenetically diverse organisms.

  1. The Effect of Sparkling Water on Intraluminal Formulation Behaviour and Systemic Drug Performance.

    PubMed

    Van Den Abeele, Jens; Brouwers, Joachim; Deloose, Eveline; Tack, Jan; Augustijns, Patrick

    2017-04-06

    In the context of mediating intra- and inter-individual variability in systemic drug exposure after oral drug administration, this small-scale, crossover study aimed to investigate the effect of drug intake with sparkling water on fasted state gastric motor function and subsequent (variability in) intraluminal and systemic drug disposition. For this purpose, healthy human volunteers were asked to ingest a conventional paracetamol tablet with either tap or sparkling water, after which antroduodenal motility as well as intraluminal and systemic drug disposition were monitored as a function of time. Ingestion of sparkling water led to the occurrence of transient pressure events in the upper gastrointestinal tract for all volunteers, although the duration and frequency of the observed effect were subject to variability. Based on systemic drug disposition parameters, drug intake with sparkling water resulted in a trend towards faster and less variable absorption of paracetamol from the gastrointestinal tract. Faster and less variable intragastric tablet disintegration, due to (i) a direct effect (i.e. in vivo dissolution rate) and/or (ii) an indirect effect (i.e. gastrointestinal motility) of sparkling water, is likely to contribute to this observation.

  2. An Isoprenylation and Palmitoylation Motif Promotes Intraluminal Vesicle Delivery of Proteins in Cells from Distant Species

    PubMed Central

    Oeste, Clara L.; Pinar, Mario; Schink, Kay O.; Martínez-Turrión, Javier; Stenmark, Harald; Peñalva, Miguel A.; Pérez-Sala, Dolores

    2014-01-01

    The C-terminal ends of small GTPases contain hypervariable sequences which may be posttranslationally modified by defined lipid moieties. The diverse structural motifs generated direct proteins towards specific cellular membranes or organelles. However, knowledge on the factors that determine these selective associations is limited. Here we show, using advanced microscopy, that the isoprenylation and palmitoylation motif of human RhoB (–CINCCKVL) targets chimeric proteins to intraluminal vesicles of endolysosomes in human cells, displaying preferential co-localization with components of the late endocytic pathway. Moreover, this distribution is conserved in distant species, including cells from amphibians, insects and fungi. Blocking lipidic modifications results in accumulation of CINCCKVL chimeras in the cytosol, from where they can reach endolysosomes upon release of this block. Remarkably, CINCCKVL constructs are sorted to intraluminal vesicles in a cholesterol-dependent process. In the lower species, neither the C-terminal sequence of RhoB, nor the endosomal distribution of its homologs are conserved; in spite of this, CINCCKVL constructs also reach endolysosomes in Xenopus laevis and insect cells. Strikingly, this behavior is prominent in the filamentous ascomycete fungus Aspergillus nidulans, in which GFP-CINCCKVL is sorted into endosomes and vacuoles in a lipidation-dependent manner and allows monitoring endosomal movement in live fungi. In summary, the isoprenylated and palmitoylated CINCCKVL sequence constitutes a specific structure which delineates an endolysosomal sorting strategy operative in phylogenetically diverse organisms. PMID:25207810

  3. Successful Treatment of a Large Pelvic Abscess Using Intraluminal VAC: A Case Report.

    PubMed

    Aras, Abbas; Celik, Sebahattin; Kiziltan, Remzi; Yilmaz, Özkan; Kotan, Çetin

    2016-04-01

    The most feared complication of the surgical treatment of rectal cancer is anastomotic leakage, which is related to high rates of mortality and morbidity. Here, we present a patient who could not be treated with surgical drainage but treated by intraluminal Vacuum Associated Closure (VAC). A 34-year-old male patient was treated for rectal cancer by low anterior resection, colorectal anastomosis, and diverting ileostomy following neoadjuvant CRT. The patient reported with a postoperative anastomotic disruption and a large pelvic abscess. Due to the continuation of foul-smell drainage inspite of perianal incision and drainage, intraluminal VAC was applied and the pelvic abscess and the foul-smell were successfully treated. The presence of an adequate anal sphincter tonus is a disadvantage in anastomotic leakage, since it prevents the emptying of the intestinal content and also precludes the drainage of the pelvic abscess. The endoluminal application of VAC, similar to the results of application of VAC in open wounds, has been demonstrated to decrease fibrin and necrotic tissue in the pelvic cavity and increase granulation tissue. VAC, which has long been used in the treatment of open wounds, is a promising method in the treatment of large pelvic abscesses due to anastomotic leakage following rectum resection.

  4. The Effect of Food on the Intraluminal Behavior of Abiraterone Acetate in Man.

    PubMed

    Geboers, Sophie; Stappaerts, Jef; Mols, Raf; Snoeys, Jan; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

    2016-09-01

    To relate the reported positive effect of food on the oral bioavailability of abiraterone to the intraluminal behavior of abiraterone acetate, an in vivo experiment was performed, in which duodenal fluids and plasma samples were collected from healthy volunteers after the administration of abiraterone acetate in fasted and postprandial conditions. The plasma concentration-time profiles confirmed the positive food effect. Nevertheless, intraduodenal concentrations of abiraterone acetate and abiraterone did not fully reflect this observation. This apparent discrepancy was explored by performing several in vitro experiments including solubility, dissolution, and transfer studies. Gastrointestinal transfer studies illustrated a positive impact of gastric processing of the abiraterone acetate formulation on the duodenal concentrations in the fasted state, which could not be observed in the postprandial condition. As the influence of gastric dissolution on the intraluminal concentrations in the small intestine declines aborally, it is most likely the superior solubility of abiraterone acetate and abiraterone in intestinal fluids of the fed state that dictates the food effect. Furthermore, N-oxide abiraterone sulfate and abiraterone sulfate appeared in the duodenum at significantly later time points than abiraterone, suggesting biliary excretion of these abiraterone metabolites; this was confirmed by in situ biliary excretion experiments in rats.

  5. 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.

  6. 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).

  7. 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.

  8. 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

  9. 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.

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

    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

    2016-01-01

    Abstract 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

  12. 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.

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

    PubMed

    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(-1)for 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.

  14. 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

  15. Multiple dose study of the combined radiosensitizers Ro 03-8799 (pimonidazole) and SR 2508 (etanidazole)

    SciTech Connect

    Bleehen, N.M.; Newman, H.F.; Maughan, T.S.; Workman, P.

    1989-04-01

    The hypoxic cell radiosensitizers Ro 03-8799 and SR 2508 have different clinical toxicities. The former produces an acute but transient central nervous system syndrome, whereas the latter produces cumulative peripheral neuropathy. Following single dose studies, an escalating multiple dose schedule using both drugs in combination showed no unexpected adverse reactions at lower doses. This study identifies the clinical tolerance and pharmacokinetics when doses in the region of the maximal tolerated dose are given to 26 patients receiving infusions of 0.75 g/m2 Ro 03-8799 and 2 g/m2 SR 2508 three times per week. At 15 doses, 3/4 patients experienced WHO grade 2 peripheral neuropathy, whereas at 12 doses 1/9 developed grade 2 and 6/9 developed grade 1 neuropathies. This represents a lower dose of SR 2508 than can be given alone suggesting that some interaction between the two drugs does exist in terms of chronic peripheral neurotoxicity. Pharmacokinetic studies show no adverse interactions between the two drugs and minimal inter-patient variation. From bivariate analysis, cumulative AUC for Ro 03-8799 has the most significant correlation with the development of peripheral neuropathy. Tumor drug concentrations normalized to the administered dose show mean values of 34 micrograms/g Ro 03-8799 and 76 micrograms/g SR 2508 30 minutes after infusion. These could be expected to produce a single dose sensitizer enhancement ratio of 1.5. The combination of the two sensitizers at the maximum tolerable dose may be expected to give an increased therapeutic efficacy over either drug alone.

  16. 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

  17. 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

  18. Differential Detection of Tumor Cells Using a Combination of Cell Rolling, Multivalent Binding, and Multiple Antibodies

    PubMed Central

    2015-01-01

    Effective quantification and in situ identification of circulating tumor cells (CTCs) in blood are still elusive because of the extreme rarity and heterogeneity of the cells. In our previous studies, we developed a novel platform that captures tumor cells at significantly improved efficiency in vitro using a unique biomimetic combination of two physiological processes: E-selectin-induced cell rolling and poly(amidoamine) (PAMAM) dendrimer-mediated strong multivalent binding. Herein, we have engineered a novel multifunctional surface, on the basis of the biomimetic cell capture, through optimized incorporation of multiple antibodies directed to cancer cell-specific surface markers, such as epithelial cell adhesion molecule (EpCAM), human epidermal growth factor receptor-2 (HER-2), and prostate specific antigen (PSA). The surfaces were tested using a series of tumor cells, MDA-PCa-2b, MCF-7, and MDA-MB-361, both in mixture in vitro and after being spiked into human blood. Our multifunctional surface demonstrated highly efficient capture of tumor cells in human blood, achieving up to 82% capture efficiency (∼10-fold enhancement than a surface with the antibodies alone) and up to 90% purity. Furthermore, the multipatterned antibodies allowed differential capturing of the tumor cells. These results support that our multifunctional surface has great potential as an effective platform that accommodates virtually any antibodies, which will likely lead to clinically significant, differential detection of CTCs that are rare and highly heterogeneous. PMID:24892731

  19. Assessing and predicting protein interactions by combining manifold embedding with multiple information integration

    PubMed Central

    2012-01-01

    Background Protein-protein interactions (PPIs) play crucial roles in virtually every aspect of cellular function within an organism. Over the last decade, the development of novel high-throughput techniques has resulted in enormous amounts of data and provided valuable resources for studying protein interactions. However, these high-throughput protein interaction data are often associated with high false positive and false negative rates. It is therefore highly desirable to develop scalable methods to identify these errors from the computational perspective. Results We have developed a robust computational technique for assessing the reliability of interactions and predicting new interactions by combining manifold embedding with multiple information integration. Validation of the proposed method was performed with extensive experiments on densely-connected and sparse PPI networks of yeast respectively. Results demonstrate that the interactions ranked top by our method have high functional homogeneity and localization coherence. Conclusions Our proposed method achieves better performances than the existing methods no matter assessing or predicting protein interactions. Furthermore, our method is general enough to work over a variety of PPI networks irrespectively of densely-connected or sparse PPI network. Therefore, the proposed algorithm is a much more promising method to detect both false positive and false negative interactions in PPI networks. PMID:22595000

  20. Further experience with modification of an intraluminal button for hands-free tracheoesophageal speech after laryngectomy.

    PubMed

    Lewin, Jan S; Montgomery, Patti C; Hutcheson, Katherine A; Chambers, Mark S

    2009-11-01

    Tracheoesophageal (TE) speech using a voice prosthesis and hands-free speaking valve with an intraluminal attachment is the gold standard for voice restoration after total laryngectomy. Modification of a standard self-retaining silicone cannula or laryngectomy button often aids in the attachment of a speaking valve within the tracheal lumen for hands-free TE speech production. An increased number of laryngectomized individuals are able to achieve hands-free TE speech when the standard length, flange, and diameter of a silicone button is customized to accommodate individual tracheostomal contours. A technique is presented for modification of a standard silicone laryngectomy button to facilitate hands-free TE speech after total laryngectomy.

  1. Proximal small bowel obstruction caused by a massive intraluminal thrombus from a stress ulcer

    PubMed Central

    Siddiky, AH; Gupta, P

    2012-01-01

    We describe a case of proximal small bowel obstruction caused by an occlusive thrombus as a result of bleeding from a duodenal ulcer, which is likely to be stress induced. Initial presentation was confused as a bleeding duodenal ulcer and resultant ileus. Such reports are incredibly rare in the literature and never has one been reported as a result of a stress ulcer. Obstructive symptoms in the acute postoperative patient may be confused for an ileus but mechanical causes must be excluded. The presence of upper gastrointestinal bleeding must not detract from that possibility. Future identification of an occlusive clot on endoscopy that is impossible to circumnavigate may benefit from intraluminal injection of thrombolytic agents to prevent obstruction but this must be weighed with the risk of exacerbating any bleeding. Clearly a risk versus benefit analysis will be necessary on an individual basis. PMID:24960721

  2. Intraluminal duodenal diverticula: collective review with report of a laparoscopic excision.

    PubMed

    Meinke, Alan Kurt; Meighan, Dennis M; Meinke, Mary E; Mirza, Nadia; Parris, Tchaiko M; Meinke, Richard K

    2013-02-01

    A comprehensive review of intraluminal duodenal diverticulum (IDD) is presented, along with a report of a completely laparoscopic excision of this duodenal abnormality as well as a report of magnetic resonance cholangiopancreatography demonstrating the classic fluoroscopic "wind sock sign" pathognomonic appearance of IDD. IDD may easily be missed unless one specifically considers this entity in patients presenting with symptoms of foregut disease. Patients with IDD typically present in the fourth decade of life with duration of symptoms less than 5 years that typically include pain, nausea and vomiting, pancreatitis, and gastrointestinal bleeding. Diagnosis usually requires imaging studies and upper gastrointestinal endoscopy. Laparoscopic excision is recommended because of superior visualization of significant intestinal anatomic abnormalities, the need for accurate ampullary localization, and the ability to facilitate complete diverticular excision while maintaining biliary and pancreatic ductal integrity. Review of surgical literature suggests that IDD results from congenital duodenal developmental abnormalities matured by long-term duodenal peristalsis.

  3. 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

  4. Nylon filament coated with paraffin for intraluminal permanent middle cerebral artery occlusion in rats.

    PubMed

    Zuo, Xia-Lin; Wu, Ping; Ji, Ai-Min

    2012-06-21

    A variety of intraluminal nylon filament has been used in rat middle cerebral artery occlusion (MCAO) models. However the lesion extent and its reproducibility vary among laboratories. The properties of nylon filament play a part of reasons for these variations. In the present study, we used paraffin-coated nylon filament for rat MCAO model, tested the effects and advanced improvement for making the rat MCAO. Forty male Sprague-Dawley (SD) rats were randomized into two groups, MCAO with traditional uncoated nylon filament (uMCAO) and MCAO with paraffin-coated nylon filament (cMCAO), three rats as normal group and sham group respectively. Assessment included mortality rates, model success rates, neurological deficit evaluation, and infarct volume. The study showed two rats died in uMCAO group, no rat died in cMCAO group within the 12h. The model success rate of uMCAO was 100%, while the uMCAO group was 55% (n=20, two died within 12h, seven rats were excluded as the brain slices showed no TTC staining due to subarachanoid hemorrhage). Neurological evaluation demonstrated group cMCAO had more worse neurological outcomes than group uMCAO, and the difference was statistically signification (p<0.05). TTC staining cMCAO group had significantly larger infarct volumes than uMCAO group, and also showed statistically significant difference (p<0.05). The result demonstrated that the paraffin-coated nylon filament intraluminal occlusion provide better occlusion of middle cerebral artery than the uncoated nylon filament, improve the consistent of model, and raise the success rate to reduce the number of experimental animals. These positive results are much encouraging and interesting.

  5. Quantitative Susceptibility Mapping Using the Multiple Dipole-Inversion Combination with k-space Segmentation Method.

    PubMed

    Sato, Ryota; Shirai, Toru; Taniguchi, Yo; Murase, Takenori; Bito, Yoshitaka; Ochi, Hisaaki

    2017-03-27

    Quantitative susceptibility mapping (QSM) is a new magnetic resonance imaging (MRI) technique for noninvasively estimating the magnetic susceptibility of biological tissue. Several methods for QSM have been proposed. One of these methods can estimate susceptibility with high accuracy in tissues whose contrast is consistent between magnitude images and susceptibility maps, such as deep gray-matter nuclei. However, the susceptibility of small veins is underestimated and not well depicted by using the above approach, because the contrast of small veins is inconsistent between a magnitude image and a susceptibility map. In order to improve the estimation accuracy and visibility of small veins without streaking artifacts, a method with multiple dipole-inversion combination with k-space segmentation (MUDICK) has been proposed. In the proposed method, k-space was divided into three domains (low-frequency, magic-angle, and high-frequency). The k-space data in low-frequency and magic-angle domains were obtained by L1-norm regularization using structural information of a pre-estimated susceptibility map. The k-space data in high-frequency domain were obtained from the pre-estimated susceptibility map in order to preserve small-vein contrasts. Using numerical simulation and human brain study at 3 Tesla, streaking artifacts and small-vein susceptibility were compared between MUDICK and conventional methods (MEDI and TKD). The numerical simulation and human brain study showed that MUDICK and MEDI had no severe streaking artifacts and MUDICK showed higher contrast and accuracy of susceptibility in small-veins compared to MEDI. These results suggest that MUDICK can improve the accuracy and visibility of susceptibility in small-veins without severe streaking artifacts.

  6. 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…

  7. Patterns of gas and liquid reflux during transient lower oesophageal sphincter relaxation: a study using intraluminal electrical impedance

    PubMed Central

    Sifrim, D; Silny, J; Holloway, R; Janssens, J

    1999-01-01

    Background—Belching has been proposed as a major mechanism underlying acid gastro-oesophageal reflux in normal subjects. However, the presence of oesophageal gas has not been measured directly but only inferred from manometry. 
Aims—To investigate, using intraluminal electrical impedance, the patterns of gas and liquid reflux during transient lower oesophageal sphincter (LOS) relaxations, the main mechanism of acid reflux in normal subjects. 
Methods—Impedance changes associated with the passage of gas were studied in vitro, and in vivo in cats. Oesophageal manometry, pH, and intraluminal electrical impedance measurements were performed in 11 normal subjects after a meal. 
Results—Gas reflux caused a sudden increase in impedance that propagated rapidly to the proximal oesophagus whereas liquid reflux induced a retrogressively propagated fall in impedance. Impedance showed gas or liquid reflux during most (102/141) transient LOS relaxations. When acid reflux occurred, impedance showed evidence of intraoesophageal retrograde flow of liquid in the majority (78%) of events. Evidence of gas retroflow was found in almost half (47%) of acid reflux episodes. When present together, however, liquid preceded gas on 44% of occasions. Overall, gas reflux occurred as the initial event in only 25% of acid reflux episodes. 
Conclusions—These findings suggest that in upright normal subjects, although belching can precipitate acid reflux, most acid reflux occurs as a primary event. 

 Keywords: belching; gastro-oesophageal reflux disease; oesophageal manometry; intraluminal electrical impedance; lower oesophageal sphincter PMID:9862825

  8. Effects of intraluminal hydrostatic pressure on L-methionine absorption in the obstructed small intestine of the rat

    SciTech Connect

    Enochsson, L.; Nylander, G.

    1986-03-01

    The effects of elevated intraluminal hydrostatic pressure on the active absorption of the amino acid selenium 75 L-methionine has been analyzed in the normal and obstructed small intestine. An intestinal loop of defined position and length was included in a recircling perfusion system from which the elimination rate of the radiolabeled amino acid was measured. Preset pressure levels within the system were maintained by a servo-controlled unit, which added or subtracted volume to keep the pressure constant. The rate of amino acid elimination increased when the nonobstructed loop was subjected to a pressure of 10 cm H2O but decreased when exposed to 20cm H2O. Using a loop of intestine subjected to 48 hours of obstruction, amino acid elimination was greatly retarded compared with that of the nonobstructed loop. By increasing the intraluminal pressure to 10 and 20 cm H2O, the elimination rate increased, equalling that of the nonobstructed gut. The results suggest that intestinal obstruction per se decreases active absorption secondary to impaired intestinal viability. Moderately increased intraluminal pressure adds a driving force to L-methionine absorption, the mechanism of which is obscure.

  9. Scaling the spectral beam combining channel by multiple diode laser stacks in an external cavity

    NASA Astrophysics Data System (ADS)

    Meng, Huicheng; Ruan, Xu; Du, Weichuan; Wang, Zhao; Lei, Fuchuan; Yu, Junhong; Tan, Hao

    2017-04-01

    Spectral beam combining of a broad area diode laser is a promising technique for direct diode laser applications. We present an experimental study of three mini-bar stacks in an external cavity on spectral beam combining in conjunction with spatial beam combining. At the pump current of 70 A, a CW output power of 579 W, spectral bandwidth of 18.8 nm and electro-optical conversion efficiency of 47% are achieved. The measured M 2 values of spectral beam combining are 18.4 and 14.7 for the fast and the slow axis, respectively. The brightness of the spectral beam combining output is 232 MW · cm‑2 · sr‑1.

  10. Intraluminal pressure patterns in the human colon assessed by high-resolution manometry

    PubMed Central

    Chen, Ji-Hong; Yu, Yuanjie; Yang, Zixian; Yu, Wen-Zhen; Chen, Wu Lan; Yu, Hui; Kim, Marie Jeong-Min; Huang, Min; Tan, Shiyun; Luo, Hesheng; Chen, Jianfeng; Chen, Jiande D. Z.; Huizinga, Jan D.

    2017-01-01

    Assessment of colonic motor dysfunction is rarely done because of inadequate methodology and lack of knowledge about normal motor patterns. Here we report on elucidation of intraluminal pressure patterns using High Resolution Colonic Manometry during a baseline period and in response to a meal, in 15 patients with constipation, chronically dependent on laxatives, 5 healthy volunteers and 9 patients with minor, transient, IBS-like symptoms but no sign of constipation. Simultaneous pressure waves (SPWs) were the most prominent propulsive motor pattern, associated with gas expulsion and anal sphincter relaxation, inferred to be associated with fast propagating contractions. Isolated pressure transients occurred in most sensors, ranging in amplitude from 5–230 mmHg. Rhythmic haustral boundary pressure transients occurred at sensors about 4–5 cm apart. Synchronized haustral pressure waves, covering 3–5 cm of the colon occurred to create a characteristic intrahaustral cyclic motor pattern at 3–6 cycles/min, propagating in mixed direction. This activity abruptly alternated with erratic patterns resembling the segmentation motor pattern of the small intestine. High amplitude propagating pressure waves (HAPWs) were too rare to contribute to function assessment in most subjects. Most patients, dependent on laxatives for defecation, were able to generate normal motor patterns in response to a meal. PMID:28216670

  11. Transcutaneous Intraluminal Impedance Measurement for Minimally Invasive Monitoring of Gastric Motility: Validation in Acute Canine Models

    PubMed Central

    Poscente, Michael D.; Wang, Gang; Filip, Dobromir; Ninova, Polya; Muench, Gregory; Yadid-Pecht, Orly; Mintchev, Martin P.; Andrews, Christopher N.

    2014-01-01

    Transcutaneous intraluminal impedance measurement (TIIM) is a new method to cutaneously measure gastric contractions by assessing the attenuation dynamics of a small oscillating voltage emitted by a battery-powered ingestible capsule retained in the stomach. In the present study, we investigated whether TIIM can reliably assess gastric motility in acute canine models. Methods. Eight mongrel dogs were randomly divided into 2 groups: half received an active TIIM pill and half received an identically sized sham capsule. After 24-hour fasting and transoral administration of the pill (active or sham), two force transducers (FT) were sutured onto the antral serosa at laparotomy. After closure, three standard cutaneous electrodes were placed on the abdomen, registering the transluminally emitted voltage. Thirty-minute baseline recordings were followed by pharmacological induction of gastric contractions using neostigmine IV and another 30-minute recording. Normalized one-minute baseline and post-neostigmine gastric motility indices (GMIs) were calculated and Pearson correlation coefficients (PCCs) between cutaneous and FT GMIs were obtained. Statistically significant GMI PCCs were seen in both baseline and post-neostigmine states. There were no significant GMI PCCs in the sham capsule test. Further chronic animal studies of this novel long-term gastric motility measurement technique are needed before testing it on humans. PMID:25574163

  12. The Relationship Between Pulsatile Flow Impingement and Intraluminal Thrombus Deposition in Abdominal Aortic Aneurysms.

    PubMed

    Lozowy, Richard J; Kuhn, David C S; Ducas, Annie A; Boyd, April J

    2017-03-01

    Direct numerical simulations were performed on four patient-specific abdominal aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics were compared to aneurysm shape and correlated with intraluminal thrombus (ILT) deposition. For three of the cases, turbulent vortex structures impinged/sheared along the anterior wall and along the posterior wall a zone of recirculating blood formed. Within the impingement region the AAA wall was devoid of ILT and remote to this region there was an accumulation of ILT. The high wall shear stress (WSS) caused by the impact of vortexes is thought to prevent the attachment of ILT. WSS from impingement is comparable to peak-systolic WSS in a normal-sized aorta and therefore may not damage the wall. Expansion occurred to a greater extent in the direction of jet impingement and the wall-normal force from the continuous impact of vortexes may contribute to expansion. It was shown that the impingement region has low oscillatory shear index (OSI) and recirculation zones can have either low or high OSI. No correlation could be identified between OSI and ILT deposition since different flow dynamics can have similar OSI values.

  13. A chemotactic gradient sequestered on endothelial heparan sulfate induces directional intraluminal crawling of neutrophils.

    PubMed

    Massena, Sara; Christoffersson, Gustaf; Hjertström, Elina; Zcharia, Eyal; Vlodavsky, Israel; Ausmees, Nora; Rolny, Charlotte; Li, Jin-Ping; Phillipson, Mia

    2010-09-16

    During infection, chemokines sequestered on endothelium induce recruitment of circulating leukocytes into the tissue where they chemotax along chemokine gradients toward the afflicted site. The aim of this in vivo study was to determine whether a chemokine gradient was formed intravascularly and influenced intraluminal neutrophil crawling and transmigration. A chemokine gradient was induced by placing a macrophage inflammatory protein-2 (MIP-2)-containing (CXCL2) gel on the cremaster muscle of anesthetized wild-type mice or heparanase-overexpressing transgenic mice (hpa-tg) with truncated heparan sulfate (HS) side chains. Neutrophil-endothelial interactions were visualized by intravital microscopy and chemokine gradients detected by confocal microscopy. Localized extravascular chemokine release (MIP-2 gel) induced directed neutrophil crawling along a chemotactic gradient immobilized on the endothelium and accelerated their recruitment into the target tissue compared with homogeneous extravascular chemokine concentration (MIP-2 superfusion). Endothelial chemokine sequestration occurred exclusively in venules and was HS-dependent, and neutrophils in hpa-tg mice exhibited random crawling. Despite similar numbers of adherent neutrophils in hpa-tg and wild-type mice, the altered crawling in hpa-tg mice was translated into decreased number of emigrated neutrophils and ultimately decreased the ability to clear bacterial infections. In conclusion, an intravascular chemokine gradient sequestered by endothelial HS effectively directs crawling leukocytes toward transmigration loci close to the infection site.

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

    PubMed

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

    2016-09-01

    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.

  15. 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.

  16. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. 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...

  19. Rainfall estimation by rain gauge-radar combination: A concurrent multiplicative-additive approach

    NASA Astrophysics Data System (ADS)

    GarcíA-Pintado, Javier; Barberá, Gonzalo G.; Erena, Manuel; Castillo, Victor M.

    2009-01-01

    A procedure (concurrent multiplicative-additive objective analysis scheme [CMA-OAS]) is proposed for operational rainfall estimation using rain gauges and radar data. On the basis of a concurrent multiplicative-additive (CMA) decomposition of the spatially nonuniform radar bias, within-storm variability of rainfall and fractional coverage of rainfall are taken into account. Thus both spatially nonuniform radar bias, given that rainfall is detected, and bias in radar detection of rainfall are handled. The interpolation procedure of CMA-OAS is built on Barnes' objective analysis scheme (OAS), whose purpose is to estimate a filtered spatial field of the variable of interest through a successive correction of residuals resulting from a Gaussian kernel smoother applied on spatial samples. The CMA-OAS, first, poses an optimization problem at each gauge-radar support point to obtain both a local multiplicative-additive radar bias decomposition and a regionalization parameter. Second, local biases and regionalization parameters are integrated into an OAS to estimate the multisensor rainfall at the ground level. The procedure is suited to relatively sparse rain gauge networks. To show the procedure, six storms are analyzed at hourly steps over 10,663 km2. Results generally indicated an improved quality with respect to other methods evaluated: a standard mean-field bias adjustment, a spatially variable adjustment with multiplicative factors, and ordinary cokriging.

  20. 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

  1. Pharmacological inhibition of p38 mitogen-activated protein kinases affects KC/CXCL1-induced intraluminal crawling, transendothelial migration, and chemotaxis of neutrophils in vivo.

    PubMed

    Xu, Najia; Hossain, Mokarram; Liu, Lixin

    2013-01-01

    p38 mitogen-activated protein kinase (MAPK) signalling is critical in the pathophysiology of a variety of inflammatory processes. Leukocyte recruitment to the site of inflammation is a multistep process governed by specific signalling cascades. After adhesion in the lumen, many leukocytes crawl to optimal sites at endothelial junctions and transmigrate to extravascular tissue in a Mac-1-dependent manner. The signalling mechanisms that regulate postadhesion steps of intraluminal crawling, transmigration, and chemotaxis in tissue remain incompletely understood. The present study explored the effect of p38 MAPK inhibitor SB203580 on various parameters of neutrophil recruitment triggered by chemokine KC (CXCL1) gradient. Neutrophil-endothelial interactions in microvasculature of murine cremaster muscle were determined using intravital microscopy and time-lapsed video analysis. SB203580 (100 nM) did not change leukocyte rolling but significantly attenuated neutrophil adhesion, emigration, and transmigration and impaired the initiation of neutrophil crawling and transmigration. In response to KC chemotactic gradient, SB203580 significantly reduced the velocity of migration and chemotaxis index of neutrophils in tissue. The upregulation of Mac-1 expression in neutrophils stimulated by KC was significantly blunted by SB203580 in vitro. Collectively, our findings demonstrate that pharmacological suppression of p38 MAPK significantly impairs multiple steps of neutrophil recruitment in vivo.

  2. Evaluating treatment effect within a multivariate stochastic ordering framework: Nonparametric combination methodology applied to a study on multiple sclerosis.

    PubMed

    Brombin, Chiara; Di Serio, Clelia

    2016-02-01

    Multiple sclerosis is an autoimmune complex disease that affects the central nervous system. It has a multitude of symptoms that are observed in different people in many different ways. At this time, there is no definite cure for multiple sclerosis. However, therapies that slow the progression of disability, controlling symptoms and helping patients to maintain a normal quality of life, are available. We will focus on relapsing-remitting multiple sclerosis patients treated with interferons or glatiramer acetate. These treatments have been shown to be effective, but their relative effectiveness has not been well established yet. To assess the superiority of a treatment, instead of classical parametric methods, we propose a statistical approach within the permutation setting and the nonparametric combination of dependent permutation tests. In this framework, we may easily handle with hypothesis testing problems for multivariate monotonic stochastic ordering. This approach has been motivated by the analysis of a large observational Italian multicentre study on multiple sclerosis, with several continuous and categorical outcomes measured at multiple time points.

  3. Automated detection of pulmonary nodules in CT: false positive reduction by combining multiple classifiers

    NASA Astrophysics Data System (ADS)

    Suárez-Cuenca, Jorge Juan; Guo, Wei; Li, Qiang

    2011-03-01

    The purpose of this study was to investigate the usefulness of various classifier combination methods for improving the performance of a CAD system for pulmonary nodule detection in CT. We employed CT cases in the publicly available lung image database consortium (LIDC) dataset, which included 85 CT cases with 110 nodules. We first used six individual classifiers for nodule detection in CT, including linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), artificial neural network (ANN), and three types of support vector machines (SVM). Five informationfusion methods were then employed to combine the classifiers' outputs for improving detection performance. The five combination methods included two supervised (likelihood ratio method and neural network) and three unsupervised ones (the mean, the product, and the majority-vote of the output scores from the six individual classifiers). Leave-one-caseout was employed to train and test individual classifiers and supervised combination methods. At a sensitivity of 80 %, the numbers of false positives per case for the six individual classifiers were 6.1 for LDA, 19.9 for QDA, 8.6 for ANN, 23.7 for SVM-dot, 17.0 for SVM-poly, and 23.35 for SVM-ANOVA; the numbers of false positives per case for the five combination methods were 3.4 for the majority-vote rule, 6.2 for the mean, 5.7 for the product, 9.7 for the neural network, and 28.1 for the likelihood ratio method. The majority-vote rule achieved higher performance levels than other combination methods. It also achieved higher performance than the best individual classifier, which is not the case for other combination methods.

  4. [Treatment of a pregnant patient after multiple trauma: rare combination with thrombotic thrombocytopenic purpura].

    PubMed

    Haffner, E; Pietsch, U; Fösel, T; Lindemann, W

    2013-02-01

    Multiple trauma during pregnancy is a relatively rare situation which poses a great challenge for the team in charge of treatment. A concomitant disease, such as thrombotic thrombocytopenic purpura (TTP) with thrombocytic coagulopathy increases the complexity of the treatment problems. This article describes the case of a 36-year-old pregnant woman referred to this hospital suffering from multiple trauma with severe liver rupture. Stabilization was achieved after an emergency Caesarean section and packing of the liver. Recurrent massive bleeding from the liver occurred after depacking and was treated successfully with recombinant factor VIIa. The concomitant TTP was treated by transfusion of fresh frozen plasma and corticosteroids. Rapid initiation of therapy was the goal to achieve hemostasis and prevent aggravation of the coagulation disorder and an unfavourable outcome despite severe thrombocytopenia.

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

    PubMed

    Kolasinski, James; Stagg, Charlotte J; 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

    2012-10-01

    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

  6. An Approach to Combining Results From Multiple Methods Motivated by the ISO GUM.

    PubMed

    Levenson, M S; Banks, D L; Eberhardt, K R; Gill, L M; Guthrie, W F; Liu, H K; Vangel, M G; Yen, J H; Zhang, N F

    2000-01-01

    The problem of determining a consensus value and its uncertainty from the results of multiple methods or laboratories is discussed. Desirable criteria of a solution are presented. A solution motivated by the ISO Guide to the Expression of Uncertainty in Measurement (ISO GUM) is introduced and applied in a detailed worked example. A Bayesian hierarchical model motivated by the proposed solution is presented and compared to the solution.

  7. Effectiveness of combining plasma exchange with continuous hemodiafiltration on acute Fatty liver of pregnancy complicated by multiple organ dysfunction.

    PubMed

    Chu, Yu-Feng; Meng, Mei; Zeng, Juan; Zhou, Hai-Yan; Jiang, Jin-Jiao; Ren, Hong-Sheng; Zhang, Ji-Cheng; Zhu, Wen-Ying; Wang, Chun-Ting

    2012-06-01

    Acute fatty liver of pregnancy (AFLP) is a rare disease of progressive hepatic insufficiency and secondary systemic complications that induce significant maternal risk. The application of combining plasma exchange (PE) and continuous hemodiafiltration (CHDF) is a novel concept for patients with AFLP. Since 2002, we have utilized the combination of PE with CHDF as adjunctive medical therapy for 11 AFLP patients with multiple organ dysfunction. Before PE and CHDF initiation, four patients had signs and symptoms of encephalopathy, four required ventilatory support, and all 11 were developing liver failure, significant renal compromise, and coagulopathy. PE combined with CHDF for patients was initiated a mean of 2 days postpartum (range, days 0-3). Daily or every other day PE combined with CHDF was undertaken on two to eight occasions for each of the 11 patients. Ten patients responded with composite clinical and laboratory improvement and were discharged to the ward, then cured and discharged from hospital; one patient died of septic shock. Average duration of hospitalization was 17 days (range, days 9-38) from time of admission to discharge; the average duration of intensive care unit was 10 days (range, days 4-23). No significant PE- and CHDF-related complications occurred. These results indicate that combing PE and CHDF in a series-parallel circuit is an effective and safe treatment for patients with severe AFLP. This finding may have important implications for the development of an effective treatment for patients with AFLP suffering multiple organ dysfunction.

  8. 43 CFR 2806.38 - Can I combine multiple grants or leases for facilities located on one site into a single grant or...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Can I combine multiple grants or leases for facilities located on one site into a single grant or lease? 2806.38 Section 2806.38 Public Lands... Communication Site Rights-Of-Way § 2806.38 Can I combine multiple grants or leases for facilities located on...

  9. Photo-decomposable Organic Nanoparticles for Combined Tumor Optical Imaging and Multiple Phototherapies

    PubMed Central

    Miao, Wenjun; Kim, Hyungjun; Gujrati, Vipul; Kim, Jin Yong; Jon, Hyeongsu; Lee, Yonghyun; Choi, Minsuk; Kim, Jinjoo; Lee, Soyoung; Lee, Dong Yun; Kang, Sukmo; Jon, Sangyong

    2016-01-01

    Combination of photodynamic therapy (PDT) with photothermal therapy (PTT) has achieved significantly improved therapeutic efficacy compared to a single phototherapy modality. However, most nanomaterials used for combined PDT/PTT are made of non-biodegradable materials (e.g., gold nanorods, carbon nanotubes, and graphenes) and may remain intact in the body for long time, raising concerns over their potential long-term toxicity. Here we report a new combined PDT/PTT nanomedicine, designated SP3NPs, that exhibit photo-decomposable, photodynamic and photothermal properties. SP3NPs were prepared by self-assembly of PEGylated cypate, comprising FDA-approved PEG and an ICG derivative. We confirmed the ability of SP3NPs to generate both singlet oxygen for a photodynamic effect and heat for photothermal therapy in response to NIR laser irradiation in vitro. Also, the unique ability of SP3NPs to undergo irreversible decomposition upon NIR laser irradiation was demonstrated. Further our experimental results demonstrated that SP3NPs strongly accumulated in tumor tissue owing to their highly PEGylated surface and relatively small size (~60 nm), offering subsequent imaging-guided combined PDT/PTT treatment that resulted in tumor eradication and prolonged survival of mice. Taken together, our SP3NPs described here may represent a novel and facile approach for next-generation theranostics with great promise for translation into clinical practice in the future. PMID:27877241

  10. 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,…

  11. Leaf structure affects a plant's appearance: combined multiple-mechanisms intensify remarkable foliar variegation.

    PubMed

    Chen, Yun-Shiuan; Chesson, Peter; Wu, Ho-Wei; Pao, Shang-Hung; Liu, Jian-Wei; Chien, Lee-Feng; Yong, Jean W H; Sheue, Chiou-Rong

    2017-03-01

    The presence of foliar variegation challenges perceptions of leaf form and functioning. But variegation is often incorrectly identified and misinterpreted. The striking variegation found in juvenile Blastus cochinchinensis (Melastomataceae) provides an instructive case study of mechanisms and their ecophysiological implications. Variegated (white and green areas, vw and vg) and non-variegated leaves (normal green leaves, ng) of seedlings of Blastus were compared structurally with microtechniques, and characterized for chlorophyll content and fluorescence. More limited study of Sonerila heterostemon (Melastomataceae) and Kaempferia pulchra (Zingiberaceae) tested the generality of the findings. Variegation in Blastus combines five mechanisms: epidermal, air space, upper mesophyll, chloroplast and crystal, the latter two being new mechanisms. All mesophyll cells (vw, vg, ng) have functional chloroplasts with dense thylakoids. The vw areas are distinguished by flatter adaxial epidermal cells and central trichomes containing crystals, the presence of air spaces between the adaxial epidermis and a colorless spongy-like upper mesophyll containing smaller and fewer chloroplasts. The vw area is further distinguished by having the largest spongy-tissue chloroplasts and fewer stomata. Both leaf types have similar total chlorophyll content and similar  F v/F m (maximum quantum yield of PSII), but vg has significantly higher F v/F m than ng. Variegation in Sonerila and Kaempferia is also caused by combined mechanisms, including the crystal type in Kaempferia. This finding of combined mechanisms in three different species suggests that combined mechanisms may occur more commonly in nature than current understanding. The combined mechanisms in Blastus variegated leaves represent intricate structural modifications that may compensate for and minimize photosynthetic loss, and reflect changing plant needs.

  12. Multiple jejunal cancers resulting from combination of germline APC and MLH1 mutations.

    PubMed

    Lindor, Noralane M; Smyrk, Tom C; Buehler, Sheila; Gunawardena, Shanaka R; Thomas, Brittany C; Limburg, Paul; Kirmani, Salman; Thibodeau, Stephen N

    2012-12-01

    Double heterozygotes for mutations in APC and a DNA mismatch repair gene are extremely rare. We report on an individual who had truncating mutations in APC and MLH1 whose clinical presentation initially resembled Familial Adenomatous Polyposis but then emerged as a novel phenotype with multiple jejunal carcinomas. We have reviewed the relevant literature on double heterozygotes and based on what has been reported to date, this phenotype was not anticipated. It may be useful for clinicians to be aware of this observation as clinical screening guidelines are proposed for such individuals.

  13. Comparison of two methods of treatment for intraluminal thermal ablation using an ultrasound cylindrical phased array.

    PubMed

    Melodelima, David; Prat, Frédéric; Birer, Alain; Theillère, Yves; Cathignol, Dominique

    2004-04-01

    Intraluminal (within the alimentary tract) thermal surgery has been shown to be a useful therapeutic option when extracorporeal focused ultrasound applicators cannot be used since their beam may not reach the target site. If plane transducers are used for the treatment of alimentary tract tumours, the applicator must be rotated in order to generate a cylindrical volume of necrosis. However, rotating these applicators and controlling their shooting direction presents technical difficulties. If tubular transducers are used it is difficult to treat arbitrary angles with a large therapeutic length. To solve these difficulties, the feasibility of an ultrasound phased array applicator has been evaluated using a cylindrical prototype (outer diameter 10.6 mm), which is composed of 16 elementary transducers working at 4.55 MHz and arranged on a quarter of the cylinder. Using this applicator it is possible to generate plane or cylindrical waves. Plane waves were generated by exciting eight successive elements of the array with appropriate delay times. The exposure direction was changed by exciting a different set of eight elements. In this way, the ultrasound beam was electronically rotated through the tissues. Cylindrical waves were generated by exciting several transducers without delay times. Imaging was provided using a miniature echographic probe. Ex vivo experiments were carried out in pig liver to compare two approaches of treatment. The first consisted of generating successive plane waves separated from each other by a 6 degrees angle. The second one consisted of exciting all the 16 elements without delay times. In the two cases, the lesions were well-defined and occupied a quarter of cylinder. In both sets of experiments, the sonication time and the intensity were 20 s and 17 W/cm(2), respectively. In the first case, the depth was up to 17 mm compared to 6 mm in the second case.

  14. High-dose-rate intraluminal brachytherapy during preoperative chemoradiation for locally advanced rectal cancers

    PubMed Central

    Tunio, Mutahir Ali; Rafi, Mansoor; Hashmi, Altaf; Mohsin, Rehan; Qayyum, Abdul; Hasan, Mujahid; Sattar, Amjad; Mubarak, Muhammad

    2010-01-01

    AIM: To determine the feasibility and safety of high dose rate intraluminal brachytherapy (HDR-ILBT) boost during preoperative chemoradiation for rectal cancer. METHODS: Between 2008 and 2009, thirty-six patients with locally advanced rectal cancer (≥ T3 or N+), were treated initially with concurrent capecitabine (825 mg/m2 oral twice daily) and pelvic external beam radiotherapy (EBRT) (45 Gy in 25 fractions), then were randomized to group A; HDR-ILBT group (n = 17) to receive 5.5-7 Gy × 2 to gross tumor volume (GTV) and group B; EBRT group (n = 19) to receive 5.4 Gy × 3 fractions to GTV with EBRT. All patients underwent total mesorectal excision. RESULTS: Grade 3 acute toxicities were registered in 12 patients (70.6%) in group A and in 8 (42.1%) in group B. Complete pathologic response of T stage (ypT0) in group A was registered in 10 patients (58.8%) and in group B, 3 patients (15.8%) had ypT0 (P < 0.0001). Sphincter preservation was reported in 6/9 patients (66.7%) in group A and in 5/10 patients (50%) in group B (P < 0.01). Overall radiological response was 68.15% and 66.04% in Group A and B, respectively. During a median follow up of 18 mo, late grade 1 and 2 sequelae were registered in 3 patients (17.6%) and 4 patients (21.1%) in the groups A and B, respectively. CONCLUSION: HDR-ILBT was found to be effective dose escalation technique in preoperative chemoradiation for rectal cancers, with higher response rates, downstaging and with manageable acute toxicities. PMID:20845511

  15. 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

  16. MALS: an efficient strategy for multiple site-directed mutagenesis employing a combination of DNA amplification, ligation and suppression PCR

    PubMed Central

    Fushan, Alexey A; Drayna, Dennis T

    2009-01-01

    Background Multiple approaches for the site-directed mutagenesis (SDM) have been developed. However, only several of them are designed for simultaneous introduction of multiple nucleotide alterations, and these are time consuming. In addition, many of the existing multiple SDM methods have technical limitations associated with type and number of mutations that can be introduced, or are technically demanding and require special chemical reagents. Results In this study we developed a quick and efficient strategy for introduction of multiple complex mutations in a target DNA without intermediate subcloning by using a combination of connecting SDM and suppression PCR. The procedure consists of sequential rounds, with each individual round including PCR amplification of target DNA with two non-overlapping pairs of oligonucleotides. The desired mutation is incorporated at the 5' end of one or both internal oligonucleotides. DNA fragments obtained during amplification are mixed and ligated. The resulting DNA mixture is amplified with external oligonucleotides that act as suppression adapters. Suppression PCR limits amplification to DNA molecules representing full length target DNA, while amplification of other types of molecules formed during ligation is suppressed. To create additional mutations, an aliquot of the ligation mixture is then used directly for the next round of mutagenesis employing internal oligonucleotides specific for another region of target DNA. Conclusion A wide variety of complex multiple mutations can be generated in a short period of time. The procedure is rapid, highly efficient and does not require special chemical reagents. Thus, MALS represents a powerful alternative to the existing methods for multiple SDM. PMID:19778447

  17. 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.

  18. Y stenting assisted coiling using a new low profile visible intraluminal support device for wide necked basilar tip aneurysms: a technical report.

    PubMed

    Conrad, Marcelo D; Brasiliense, Leonardo B C; Richie, Alexa N; Hanel, Ricardo A

    2014-05-01

    Many endovascular techniques have been described in recent years for the management of wide necked aneurysms. The Y stent assisted technique has been generally used for coil embolization of wide necked bifurcation aneurysms. This technique was first described for the treatment of basilar tip aneurysms in combination with several different devices, demonstrating encouraging results. We report the results of the first two cases of wide necked basilar tip aneurysms treated with Y stent assisted coil embolization using a new low profile visible intraluminal stent (LVIS Jr; MicroVention, Tustin, California, USA) delivered through a 0.017 inch microcatheter. We also reviewed the literature comparing other endovascular techniques (coiling alone, stent assisted coiling, and Y stent assisted coiling) for wide necked aneurysms. The LVIS Jr device offers a new option for the treatment of these challenging lesions, with clear advantages over currently available intracranial stents. Larger series and long term results are needed to confirm the applicability and durability of this technique/technology.

  19. Synergistic Combinations of Multiple Chemotherapeutic Agents in High Capacity Poly(2-oxazoline) Micelles

    PubMed Central

    Han, Yingchao; He, Zhijian; Schulz, Anita; Bronich, Tatiana K.; Jordan, Rainer; Luxenhofer, Robert; Kabanov, Alexander V.

    2012-01-01

    Many effective drugs for cancer treatment are poorly water-soluble. In combination chemotherapy, needed excipients in additive formulations are often toxic and restrict their applications in clinical intervention. Here, we report on amphiphilic poly(2-oxazoline)s (POx) micelles as a promising high capacity delivery platform for multi-drug cancer chemotherapy. A variety of binary and ternary drugs combinations of paclitaxel (PTX), docetaxel (DTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), etoposide (ETO) and bortezomib (BTZ) were solubilized in defined polymeric micelles achieving unprecedented high total loading capacities of up to 50 wt.% drug per final formulation. Multi-drug loaded POx micelles showed enhanced stability in comparison to single-drug loaded micelles. Drug ratio dependent synergistic cytotoxicity of micellar ETO/17-AAG was observed in MCF-7 cancer cells and of micellar BTZ/17-AAG in MCF-7, PC3, MDA-MB-231 and HepG2 cells. PMID:22681126

  20. A new estimation approach for combining epidemiological data from multiple sources

    PubMed Central

    Huang, Hui; Ma, Xiaomei; Waagepetersen, Rasmus; Holford, Theodore R.; Wang, Rong; Risch, Harvey; Mueller, Lloyd

    2014-01-01

    We propose a novel two-step procedure to combine epidemiological data obtained from diverse sources with the aim to quantify risk factors affecting the probability that an individual develops certain disease such as cancer. In the first step we derive all possible unbiased estimating functions based on a group of cases and a group of controls each time. In the second step, we combine these estimating functions efficiently in order to make full use of the information contained in data. Our approach is computationally simple and flexible. We illustrate its efficacy through simulation and apply it to investigate pancreatic cancer risks based on data obtained from the Connecticut Tumor Registry, a population-based case-control study, and the Behavioral Risk Factor Surveillance System which is a state-based system of health surveys. PMID:24683281

  1. 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.

  2. 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

    2015-08-07

    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.

  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. 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.

  5. Identification of multiple faults in rotating machinery based on minimum entropy deconvolution combined with spectral kurtosis

    NASA Astrophysics Data System (ADS)

    He, Dan; Wang, Xiufeng; Li, Shancang; Lin, Jing; Zhao, Ming

    2016-12-01

    Due to the complexity of mechanical system, multiple faults may co-exist in a rotating machinery, where vibration is commonly used for diagnosis. The measured vibration signal could be considered as a result of convolution process of malfunction induced periodic impact signal and resonant response of the mechanical component, and deconvolution is an effective way to restore impulses. The minimum entropy deconvolution (MED) has been shown to be an effective deconvolution method and has been employed in rotating machinery fault diagnosis. Nevertheless, the simulation in this paper shows that the MED is unable to identify multi-faults of rotating machinery fully when different faults excite different resonance frequencies. To overcome this shortcoming, a new multi-faults detection method based on Spectral kurtosis (SK) and MED is proposed. The effectiveness of the proposed method is validated by simulation data and field signals from a vacuum pump.

  6. 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.

  7. 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

  8. [Research on the method of choosing optimum wavelengths combination by using multiple scattering correction technique].

    PubMed

    Lu, Yong-jun; Qu, Yan-ling; Feng, Zhi-qing; Song, Min

    2007-01-01

    Multiple scattering correction(MSC) algorithm can be used effectively to remove the effect of scattering due to the physical factors such as the density and humidity of sample granule, and as a result the ratio of signal to noise is improved greatly. Meantime correlation spectrum plays a important role in the choice of optimum wavelength set because it describes the linear correlationship between the absorbance and concentration of the sample's ingredient under analysis. However, the correlation spectrum obtained by unitary linear regression(ULR) at single wavelength channel can be easily affected by the scattering so as to cover up the characteristic linear information of the sample. In order to solve the problem in the present paper MSC was applied to obtain useful signal and suppress noise of correlation spectrum. Through the careful calibration experiment of ginseng sample this idea has proved to be correct, and satisfactory result was obtained.

  9. 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

  10. Phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma.

    PubMed

    Berdeja, Jesus G; Hart, Lowell L; Mace, Joseph R; Arrowsmith, Edward R; Essell, James H; Owera, Rami S; Hainsworth, John D; Flinn, Ian W

    2015-05-01

    The purpose of this study was to assess the safety and efficacy of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma. Patients with multiple myeloma who had relapsed after at least one prior treatment were eligible to participate. In the dose escalation part of the study a standard 3+3 design was used to determine the maximum tolerated dose of four planned dose levels of the combination of carfilzomib and panobinostat. Panobinostat was administered on days 1, 3, 5, 15, 17, and 19. Carfilzomib was administered on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Treatment was continued until progression or intolerable toxicity. Forty-four patients were accrued into the trial, 13 in the phase I part and 31 in the phase II part of the study. The median age of the patients was 66 years and the median number of prior therapies was five. The expansion dose was established as 30 mg panobinostat, 20/45 mg/m(2) carfilzomib. The overall response rate was 67% for all patients, 67% for patients refractory to prior proteasome inhibitor treatment and 75% for patients refractory to prior immune modulating drug treatment. At a median follow up of 17 months, median progression-free survival was 7.7 months, median time to progression was 7.7 months, and median overall survival had not been reached. The regimen was well tolerated, although there were several panobinostat dose reductions. In conclusion, the combination of panobinostat and carfilzomib is feasible and effective in patients with relapsed/refractory multiple myeloma. (Trial registered at ClinicalTrials.gov: NCT01496118).

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  12. Multiple Channel Laser Beam Combination and Phasing Using Stimulated Brillouin Scattering in Optical Fibers

    DTIC Science & Technology

    2005-12-01

    Mandel’shtam–Brillouin scattering,” JETP Lett ., 15, 109-112, 1972. 41 . Hellwarth, R. W., “Phase conjugation by stimulated backscattering,” ch. 7, Optical...wavefront-reversing mirrors,” Sov . Phys . JETP , 52, 847-851, 1980. 79. Valley, M., G. Lombardi, and R. Aprahamian, “Beam combination by stimulated...Thomas, and R. Byer, Monolithic, “Unidirectional single-mode Nd:YAG ring laser”, Opt. Lett ., 10, 65-67, 1985 . 56. Imai, M. and E. H. Hara

  13. Multiple Channel Laser Beam Combination and Phasing Using Stimulated Brillouin Scattering in Optical Fibers

    DTIC Science & Technology

    2005-12-22

    Mandel’shtam–Brillouin scattering,” JETP Lett ., 15, 109-112, 1972. 41 . Hellwarth, R. W., “Phase conjugation by stimulated backscattering,” ch. 7, Optical...wavefront-reversing mirrors,” Sov . Phys . JETP , 52, 847-851, 1980. 79. Valley, M., G. Lombardi, and R. Aprahamian, “Beam combination by stimulated...Thomas, and R. Byer, Monolithic, “Unidirectional single-mode Nd:YAG ring laser”, Opt. Lett ., 10, 65-67, 1985 . 56. Imai, M. and E. H. Hara

  14. 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.

  15. Design of temperature-independent arrayed waveguide gratings based on the combination of multiple types of waveguide.

    PubMed

    Huang, Huamao; Ho, Seng-Tiong; Huang, Dexiu; Tu, Yongming; Liu, Wen

    2010-06-01

    We develop a design theory for a temperature-independent arrayed waveguide grating (TI-AWG) based on the combination of multiple types of waveguide. Each type of waveguide has a path-length difference between adjacent arrayed waveguides, and the path-length difference ratio is introduced as tuning parameter. A TI-AWG with Si wire and slot waveguides is given as an example. The thermal spectra shift of the TI-AWG can be tuned from redshift to blueshift in an ultralarge range, and the modified interference order can be reduced or enhanced. The device size is about one-fifth that of the narrow-wide-wire design that uses a combination of narrow and wide Si wire waveguides. The results are verified by the simulation of prototype devices via a two-dimensional finite-difference time-domain program.

  16. 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

  17. Comparison of multichannel intraluminal impedance-pH monitoring and reflux scintigraphy in pediatric patients with suspected gastroesophageal reflux

    PubMed Central

    Uslu Kızılkan, Nuray; Bozkurt, Murat Fani; Saltık Temizel, Inci Nur; Demir, Hülya; Yüce, Aysel; Caner, Biray; Özen, Hasan

    2016-01-01

    AIM To evaluate the agreement of multichannel intraluminal impedance-pH monitoring (MII-pHM) and gastroesophageal reflux scintigraphy (GES) for the diagnosis of gastroesophageal reflux disease. METHODS Seventy-five consecutive patients with suspected gastroesophageal reflux disease (GERD) underwent 24-h combined MII-pHM recording and one hour radionuclide scintigraphy during the course of the MII-pHM study. Catheters with 6 impedance channels and 1 pH sensor were placed transnasally. Impedance and pH data analysis were performed automatically and manually. For impedance monitoring, reflux was defined as a retrograde 50% drop in impedance, starting distally and propagating retrogradely to at least the next two more proximal measuring channels. Reflux index (RI, percentage of the entire record that esophageal pH is < 4.0) greater than 4.2% for pHM and number of refluxes more than 50 for 24 h for MII were accepted as positive test results. At scintigraphy, 240 frames of 15 seconds duration were acquired in the supine position. Gastroesophageal reflux was defined as at least one reflux episode in the esophagus. After scintigraphic evaluation, impedance-pH recordings and scintigraphic images were evaluated together and agreement between tests were evaluated with Cohen’s kappa. RESULTS Sufficient data was obtained from 60 (80%) patients (34 male, 56.7%) with a mean age of 8.7 ± 3.7 years (range: 2.5-17.3 years; median: 8.5 years). Chronic cough, nausea, regurgitation and vomiting were the most frequent symptoms. The mean time for recording of MII-pHM was 22.8 ± 2.4 h (range: 16-30 h; median: 22.7 h). At least one test was positive in 57 (95%) patients. According to diagnostic criteria, GERD was diagnosed in 34 (57.7%), 44 (73.3%), 47 (78.3%) and 51 (85%) patients by means of pHM, MII, GES and MII-pHM, respectively. The observed percentage agreements/κ values for GES and pHM, GES and MII, GES and MII-pHM, and MII and pHM are 48.3%/-0.118; 61.7%/-0.042; 73

  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. Accessing the genomic information of unculturable oceanic picoeukaryotes by combining multiple single cells

    PubMed Central

    Mangot, Jean-François; Logares, Ramiro; Sánchez, Pablo; Latorre, Fran; Seeleuthner, Yoann; Mondy, Samuel; Sieracki, Michael E.; Jaillon, Olivier; Wincker, Patrick; Vargas, Colomban de; Massana, Ramon

    2017-01-01

    Pico-sized eukaryotes play key roles in the functioning of marine ecosystems, but we still have a limited knowledge on their ecology and evolution. The MAST-4 lineage is of particular interest, since it is widespread in surface oceans, presents ecotypic differentiation and has defied culturing efforts so far. Single cell genomics (SCG) are promising tools to retrieve genomic information from these uncultured organisms. However, SCG are based on whole genome amplification, which normally introduces amplification biases that limit the amount of genomic data retrieved from a single cell. Here, we increase the recovery of genomic information from two MAST-4 lineages by co-assembling short reads from multiple Single Amplified Genomes (SAGs) belonging to evolutionary closely related cells. We found that complementary genomic information is retrieved from different SAGs, generating co-assembly that features >74% of genome recovery, against about 20% when assembled individually. Even though this approach is not aimed at generating high-quality draft genomes, it allows accessing to the genomic information of microbes that would otherwise remain unreachable. Since most of the picoeukaryotes still remain uncultured, our work serves as a proof-of-concept that can be applied to other taxa in order to extract genomic data and address new ecological and evolutionary questions. PMID:28128359

  20. Discovery of multiple hidden allosteric sites by combining Markov state models and experiments.

    PubMed

    Bowman, Gregory R; Bolin, Eric R; Hart, Kathryn M; Maguire, Brendan C; Marqusee, Susan

    2015-03-03

    The discovery of drug-like molecules that bind pockets in proteins that are not present in crystallographic structures yet exert allosteric control over activity has generated great interest in designing pharmaceuticals that exploit allosteric effects. However, there have only been a small number of successes, so the therapeutic potential of these pockets--called hidden allosteric sites--remains unclear. One challenge for assessing their utility is that rational drug design approaches require foreknowledge of the target site, but most hidden allosteric sites are only discovered when a small molecule is found to stabilize them. We present a means of decoupling the identification of hidden allosteric sites from the discovery of drugs that bind them by drawing on new developments in Markov state modeling that provide unprecedented access to microsecond- to millisecond-timescale fluctuations of a protein's structure. Visualizing these fluctuations allows us to identify potential hidden allosteric sites, which we then test via thiol labeling experiments. Application of these methods reveals multiple hidden allosteric sites in an important antibiotic target--TEM-1 β-lactamase. This result supports the hypothesis that there are many as yet undiscovered hidden allosteric sites and suggests our methodology can identify such sites, providing a starting point for future drug design efforts. More generally, our results demonstrate the power of using Markov state models to guide experiments.

  1. Accessing the genomic information of unculturable oceanic picoeukaryotes by combining multiple single cells.

    PubMed

    Mangot, Jean-François; Logares, Ramiro; Sánchez, Pablo; Latorre, Fran; Seeleuthner, Yoann; Mondy, Samuel; Sieracki, Michael E; Jaillon, Olivier; Wincker, Patrick; Vargas, Colomban de; Massana, Ramon

    2017-01-27

    Pico-sized eukaryotes play key roles in the functioning of marine ecosystems, but we still have a limited knowledge on their ecology and evolution. The MAST-4 lineage is of particular interest, since it is widespread in surface oceans, presents ecotypic differentiation and has defied culturing efforts so far. Single cell genomics (SCG) are promising tools to retrieve genomic information from these uncultured organisms. However, SCG are based on whole genome amplification, which normally introduces amplification biases that limit the amount of genomic data retrieved from a single cell. Here, we increase the recovery of genomic information from two MAST-4 lineages by co-assembling short reads from multiple Single Amplified Genomes (SAGs) belonging to evolutionary closely related cells. We found that complementary genomic information is retrieved from different SAGs, generating co-assembly that features >74% of genome recovery, against about 20% when assembled individually. Even though this approach is not aimed at generating high-quality draft genomes, it allows accessing to the genomic information of microbes that would otherwise remain unreachable. Since most of the picoeukaryotes still remain uncultured, our work serves as a proof-of-concept that can be applied to other taxa in order to extract genomic data and address new ecological and evolutionary questions.

  2. The transient intraluminal filament middle cerebral artery occlusion model as a model of endovascular thrombectomy in stroke.

    PubMed

    Sutherland, Brad A; Neuhaus, Ain A; Couch, Yvonne; Balami, Joyce S; DeLuca, Gabriele C; Hadley, Gina; Harris, Scarlett L; Grey, Adam N; Buchan, Alastair M

    2016-02-01

    The clinical relevance of the transient intraluminal filament model of middle cerebral artery occlusion (tMCAO) has been questioned due to distinct cerebral blood flow profiles upon reperfusion between tMCAO (abrupt reperfusion) and alteplase treatment (gradual reperfusion), resulting in differing pathophysiologies. Positive results from recent endovascular thrombectomy trials, where the occluding clot is mechanically removed, could revolutionize stroke treatment. The rapid cerebral blood flow restoration in both tMCAO and endovascular thrombectomy provides clinical relevance for this pre-clinical model. Any future clinical trials of neuroprotective agents as adjuncts to endovascular thrombectomy should consider tMCAO as the model of choice to determine pre-clinical efficacy.

  3. [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.

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

    PubMed

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

    2012-01-01

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

  5. Validity of Laser Doppler Flowmetry in Predicting Outcome in Murine Intraluminal Middle Cerebral Artery Occlusion Stroke

    PubMed Central

    Hedna, Vishnumurthy Shushrutha; Ansari, Saeed; Shahjouei, Shima; Cai, Peter Y.; Ahmad, Abdullah Shafique; Mocco, J; Qureshi, Adnan I.

    2015-01-01

    Background Laser Doppler flowmetry (LDF) can reliably reflect brain perfusion in experimental stroke by monitoring both the degree and the duration of relative regional cerebral blood flow (rCBF). Variation in rCBF was continuously monitored in 68 mice undergoing middle cerebral artery occlusion (MCAO) and 25 mice undergoing sham-operation and documented as LDF (%). Transcranial LDF changes in the territory of right middle cerebral artery during MCAO procedure were correlated with corrected infarct volume (CIV) and neurological deficit score (NDS). Methods Ninety-three C57BL/6 mice (Harlan Laboratories, Indianapolis, IN) between 9 and 11 weeks old were randomly selected and assigned to either MCAO for 45 minutes (n = 68) or sham group (n = 25). Ischemia was induced using the transient intraluminal filament model of MCAO based on Koizumi’s method and transcranial LDF was used to measure CBF during the procedure. Neurological deficits were measured at 2 and 23 hours after MCA reperfusion with NDS and 2% triphenyltetrazolium chloride (TTC) staining of carefully dissected brains was performed at 23 hours after reperfusion to determine infarct area. Results After common carotid artery occlusion (CCAO), there was a negative association between LDF drop from base line and NDS at 2 hours (r = −0.43, P = 0.038) and 23 hours (r = −0.61, P = 0.003). Also, a negative correlation was noted between MCA reperfusion LDF and NDS at 23 hours (r = −0.53, P = 0.001). Moreover, post-MCA reperfusion LDF had a positive association with initial CCAO LDF (r = 0.761, P = 0.000) and MCA occlusion LDF (r = 0.31, P = 0.036) in predicting neurological outcome. NDS at 23 hours corresponded well with the infarct volume (r = 0.31, P = 0.005). Conclusions Greater augmentation of rCBF after MCA reperfusion was associated with improved neurological deficit scoring. Interestingly, greater reduction of regional cerebral blood flow after CCAO was also associated with improved neurological

  6. Isotropic 3D Black Blood MRI of Abdominal Aortic Aneurysm Wall and Intraluminal Thrombus

    PubMed Central

    Zhu, Chengcheng; Haraldsson, Henrik; Faraji, Farshid; Owens, Christopher; Gasper, Warren; Ahn, Sinyeob; Liu, Jing; Laub, Gerhard; Hope, Michael D.; Saloner, David

    2015-01-01

    Introduction The aortic wall and intraluminal thrombus (ILT) have been increasingly studied as potential markers of progressive disease with abdominal aortic aneurysms (AAAs). Our goal was to develop a high resolution, 3D black blood MR technique for AAA wall and ILT imaging within a clinically acceptable scan time. Methods Twenty two patients with AAAs (maximal diameter 4.3±1.0cm), along with five healthy volunteers, were imaged at 3T with a 3D T1-weighted fast-spin-echo sequence using variable flip angle trains (SPACE) with a preparation pulse (DANTE) for suppressing blood signal. Volunteers and ten patients were also scanned with SPACE alone for comparison purposes. The signal to noise ratio (SNR) and the aortic wall/ILT to lumen contrast to noise ratio (CNR) were measured. Qualitative image scores (1–4 scale) assessing the inner lumen and outer wall boundaries of AAA were performed by two blinded reviewers. In patients with ILT, the ratio of ILT signal intensity (ILTSI) over psoas muscle SI (MuscleSI) was calculated, and the signal heterogeneity of ILT was quantified as standard deviation (SD) over the mean. Results All subjects were imaged successfully with an average scan time of 7.8±0.7 minutes. The DANTE preparation pulse for blood suppression substantially reduced flow artifacts in SPACE with lower lumen SNR (8.8 vs. 21.4, p<0.001) and improved the wall/ILT to lumen CNR (9.9 vs. 6.3, p<0.001) in patients. Qualitative assessment showed improved visualization of lumen boundaries (73% higher scores on average, p=0.01) and comparable visualization of outer wall boundary (p>0.05). ILT was present in ten patients, with relatively high signal and a wide SD (average ILTSI/MuscleSI 1.42±0.48 (range 0.75–2.11) ) and with SD/mean of 27.7%±6.6% (range 19.6% – 39.4%). Conclusion High resolution, 3D black blood MRI of AAAs can be achieved in a clinical accepted scan time with reduction of flow artifacts using the DANTE preparation pulse. Signal characteristics

  7. 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.

  8. 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/.

  9. 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.

  10. Behavioral phenotypes in schizophrenic animal models with multiple combinations of genetic and environmental factors.

    PubMed

    Hida, Hirotake; Mouri, Akihiro; Noda, Yukihiro

    2013-01-01

    Schizophrenia is a multifactorial psychiatric disorder in which both genetic and environmental factors play a role. Genetic [e.g., Disrupted-in-schizophrenia 1 (DISC1), Neuregulin-1 (NRG1)] and environmental factors (e.g., maternal viral infection, obstetric complications, social stress) may act during the developmental period to increase the incidence of schizophrenia. In animal models, interactions between susceptibility genes and the environment can be controlled in ways not possible in humans; therefore, such models are useful for investigating interactions between or within factors in the pathogenesis and pathophysiology of schizophrenia. We provide an overview of schizophrenic animal models investigating interactions between or within factors. First, we reviewed gene-environment interaction animal models, in which schizophrenic candidate gene mutant mice were subjected to perinatal immune activation or adolescent stress. Next, environment-environment interaction animal models, in which mice were subjected to a combination of perinatal immune activation and adolescent administration of drugs, were described. These animal models showed interaction between or within factors; behavioral changes, which were obscured by each factor, were marked by interaction of factors and vice versa. Appropriate behavioral approaches with such models will be invaluable for translational research on novel compounds, and also for providing insight into the pathogenesis and pathophysiology of schizophrenia.

  11. A three monoclonal antibody combination potently neutralizes multiple botulinum neurotoxin serotype F subtypes

    PubMed Central

    Fan, Yongfeng; Garcia-Rodriguez, Consuelo; Lou, Jianlong; Wen, Weihua; Conrad, Fraser; Zhai, Wenwu; Smith, Theresa J.; Smith, Leonard A.

    2017-01-01

    Human botulism is primarily caused by botulinum neurotoxin (BoNT) serotypes A, B and E, with around 1% caused by serotype F (BoNT/F). BoNT/F comprises at least seven different subtypes with the amino acid sequence difference between subtypes as high as 36%. The sequence differences present a significant challenge for generating monoclonal antibodies (mAbs) that can bind, detect and neutralize all BoNT/F subtypes. We used repertoire cloning of immune mouse antibody variable (V) regions and yeast display to generate a panel of 33 lead single chain Fv (scFv) mAbs that bound one or more BoNT/F subtypes with a median equilibrium dissociation constant (KD) of 4.06 × 10−9 M. By diversifying the V-regions of the lead mAbs and selecting for cross reactivity we generated five mAbs that bound each of the seven subtypes. Three scFv binding non-overlapping epitopes were converted to IgG that had KD for the different BoNT/F subtypes ranging from 2.2×10−8 M to 1.47×10−12 pM. An equimolar combination of the mAbs was able to potently neutralize BoNT/F1, F2, F4 and F7 in the mouse neutralization assay. The mAbs have potential utility as diagnostics capable of recognizing the known BoNT/F subtypes and could be developed as antitoxins to prevent and treat type F botulism. PMID:28323873

  12. 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.

  13. A three monoclonal antibody combination potently neutralizes multiple botulinum neurotoxin serotype F subtypes.

    PubMed

    Fan, Yongfeng; Garcia-Rodriguez, Consuelo; Lou, Jianlong; Wen, Weihua; Conrad, Fraser; Zhai, Wenwu; Smith, Theresa J; Smith, Leonard A; Marks, James D

    2017-01-01

    Human botulism is primarily caused by botulinum neurotoxin (BoNT) serotypes A, B and E, with around 1% caused by serotype F (BoNT/F). BoNT/F comprises at least seven different subtypes with the amino acid sequence difference between subtypes as high as 36%. The sequence differences present a significant challenge for generating monoclonal antibodies (mAbs) that can bind, detect and neutralize all BoNT/F subtypes. We used repertoire cloning of immune mouse antibody variable (V) regions and yeast display to generate a panel of 33 lead single chain Fv (scFv) mAbs that bound one or more BoNT/F subtypes with a median equilibrium dissociation constant (KD) of 4.06 × 10-9 M. By diversifying the V-regions of the lead mAbs and selecting for cross reactivity we generated five mAbs that bound each of the seven subtypes. Three scFv binding non-overlapping epitopes were converted to IgG that had KD for the different BoNT/F subtypes ranging from 2.2×10-8 M to 1.47×10-12 pM. An equimolar combination of the mAbs was able to potently neutralize BoNT/F1, F2, F4 and F7 in the mouse neutralization assay. The mAbs have potential utility as diagnostics capable of recognizing the known BoNT/F subtypes and could be developed as antitoxins to prevent and treat type F botulism.

  14. 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.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22686430

  16. 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

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

  17. 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, 2010 CFR

    2010-01-01

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

  18. 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

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

  19. 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

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

  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, 2012 CFR

    2012-01-01

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

  1. Insulin combined with Chinese medicine improves glycemic outcome through multiple pathways in patients with type 2 diabetes mellitus

    PubMed Central

    Zhang, Xinxia; Liu, Ya; Xiong, Daqian; Xie, Chunguang

    2015-01-01

    Introduction/Aims Insufficient insulin secretion or inefficient insulin response are responsible for the clinical outcome of type 2 diabetes mellitus. Administration of insulin alone is prone to cause secondary effects, resulting in an unsatisfactory outcome. Shen-Qi-Formula (SQF), a well-known Chinese medicinal formula, has been used for diabetic treatment for a long time. The present study was designed to investigate whether SQF in combination with insulin improved the clinical outcome of type 2 diabetes mellitus, and what mechanisms were possibly involved in the treatment. Materials and Methods A total of 219 patients were included in the study. Of these, 110 patients were treated with insulin monotherapy, and 109 with the combination therapy of SQF and insulin. Before and after 12-week treatment, the fasting blood glucose, postprandial blood glucose, β-cell function, insulin resistance and blood lipids were measured. Results The 12 weeks of SQF treatment in combination with insulin significantly decreased the fasting and postprandial blood glucose levels. Insulin secretion was not increased after the treatment, but β-cell function and insulin resistance were obviously improved. Furthermore, 12 weeks of treatment with SQF and insulin improved the levels of glucagon-like peptide-1, oxidative stress, blood lipids, coagulation function and bodyweight. Conclusion The results from our study showed that the combination therapy of SQF and insulin significantly improved the clinical outcome of type 2 diabetes mellitus compared with insulin monotherapy. The mechanism of improvement was possibly involved in the multiple pathways. PMID:26543546

  2. Outage Performance and Average Symbol Error Rate of M-QAM for Maximum Ratio Combining with Multiple Interferers

    NASA Astrophysics Data System (ADS)

    Ahn, Kyung Seung

    In this paper, we investigate the performance of maximum ratio combining (MRC) in the presence of multiple cochannel interferences over a flat Rayleigh fading channel. Closed-form expressions of signal-to-interference-plus-noise ratio (SINK), outage probability, and average symbol error rate (SER) of quadrature amplitude modulation (QAM) with Mary signaling are obtained for unequal-power interference-to-noise ratio (INR). We also provide an upper-bound for the average SER using moment generating function (MGF) of the SINR. Moreover, we quantify the array gain loss between pure MRC (MRC system in the absence of CCI) and MRC system in the presence of CCI. Finally, we verify our analytical results by numerical simulations.

  3. 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.

  4. 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.

  5. Computational approaches for protein function prediction: a combined strategy from multiple sequence alignment to molecular docking-based virtual screening.

    PubMed

    Pierri, Ciro Leonardo; Parisi, Giovanni; Porcelli, Vito

    2010-09-01

    The functional characterization of proteins represents a daily challenge for biochemical, medical and computational sciences. Although finally proved on the bench, the function of a protein can be successfully predicted by computational approaches that drive the further experimental assays. Current methods for comparative modeling allow the construction of accurate 3D models for proteins of unknown structure, provided that a crystal structure of a homologous protein is available. Binding regions can be proposed by using binding site predictors, data inferred from homologous crystal structures, and data provided from a careful interpretation of the multiple sequence alignment of the investigated protein and its homologs. Once the location of a binding site has been proposed, chemical ligands that have a high likelihood of binding can be identified by using ligand docking and structure-based virtual screening of chemical libraries. Most docking algorithms allow building a list sorted by energy of the lowest energy docking configuration for each ligand of the library. In this review the state-of-the-art of computational approaches in 3D protein comparative modeling and in the study of protein-ligand interactions is provided. Furthermore a possible combined/concerted multistep strategy for protein function prediction, based on multiple sequence alignment, comparative modeling, binding region prediction, and structure-based virtual screening of chemical libraries, is described by using suitable examples. As practical examples, Abl-kinase molecular modeling studies, HPV-E6 protein multiple sequence alignment analysis, and some other model docking-based characterization reports are briefly described to highlight the importance of computational approaches in protein function prediction.

  6. 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.

  7. 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

  8. Combined genetic algorithm and multiple linear regression (GA-MLR) optimizer: Application to multi-exponential fluorescence decay surface.

    PubMed

    Fisz, Jacek J

    2006-12-07

    The optimization approach based on the genetic algorithm (GA) combined with multiple linear regression (MLR) method, is discussed. The GA-MLR optimizer is designed for the nonlinear least-squares problems in which the model functions are linear combinations of nonlinear functions. GA optimizes the nonlinear parameters, and the linear parameters are calculated from MLR. GA-MLR is an intuitive optimization approach and it exploits all advantages of the genetic algorithm technique. This optimization method results from an appropriate combination of two well-known optimization methods. The MLR method is embedded in the GA optimizer and linear and nonlinear model parameters are optimized in parallel. The MLR method is the only one strictly mathematical "tool" involved in GA-MLR. The GA-MLR approach simplifies and accelerates considerably the optimization process because the linear parameters are not the fitted ones. Its properties are exemplified by the analysis of the kinetic biexponential fluorescence decay surface corresponding to a two-excited-state interconversion process. A short discussion of the variable projection (VP) algorithm, designed for the same class of the optimization problems, is presented. VP is a very advanced mathematical formalism that involves the methods of nonlinear functionals, algebra of linear projectors, and the formalism of Fréchet derivatives and pseudo-inverses. Additional explanatory comments are added on the application of recently introduced the GA-NR optimizer to simultaneous recovery of linear and weakly nonlinear parameters occurring in the same optimization problem together with nonlinear parameters. The GA-NR optimizer combines the GA method with the NR method, in which the minimum-value condition for the quadratic approximation to chi(2), obtained from the Taylor series expansion of chi(2), is recovered by means of the Newton-Raphson algorithm. The application of the GA-NR optimizer to model functions which are multi

  9. Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma.

    PubMed

    Chauhan, Dharminder; Singh, Ajita V; Ciccarelli, Bryan; Richardson, Paul G; Palladino, Michael A; Anderson, Kenneth C

    2010-01-28

    Our recent study demonstrated that a novel proteasome inhibitor NPI-0052 is distinct from bortezomib (Velcade) and, importantly, triggers apoptosis in multiple myeloma (MM) cells resistant to bortezomib. Here we demonstrate that combining NPI-0052 and lenalidomide (Revlimid) induces synergistic anti-MM activity in vitro using MM-cell lines or patient MM cells. NPI-0052 plus lenalidomide-induced apoptosis is associated with (1) activation of caspase-8, caspase-9, caspase-12, caspase-3, and poly(ADP) ribose polymerase; (2) activation of BH-3 protein BIM; (3) translocation of BIM to endoplasmic reticulum; (4) inhibition of migration of MM cells and angiogenesis; and (5) suppression of chymotrypsin-like, caspase-like, and trypsin-like proteasome activities. Importantly, blockade of BIM using siRNA significantly abrogates NPI-0052 plus lenalidomide-induced apoptosis. Furthermore, studies using biochemical inhibitors of caspase-8 versus caspase-9 demonstrate that NPI-0052 plus lenalidomide-triggered apoptosis is primarily dependent on caspase-8 signaling. In animal tumor model studies, low-dose combination of NPI-0052 and lenalidomide is well tolerated, significantly inhibits tumor growth, and prolongs survival. Taken together, our study provides the preclinical rationale for clinical protocols evaluating lenalidomide together with NPI-0052 to improve patient outcome in MM.

  10. High Structural Stress and Presence of Intraluminal Thrombus Predict Abdominal Aortic Aneurysm 18F-FDG Uptake

    PubMed Central

    Huang, Yuan; Elkhawad, Maysoon; Tarkin, Jason M.; Joshi, Nikhil; Boyle, Jonathan R.; Buscombe, John R.; Fryer, Timothy D.; Zhang, Yongxue; Park, Ah Yeon; Wilkinson, Ian B.; Newby, David E.; Gillard, Jonathan H.

    2016-01-01

    Background— Abdominal aortic aneurysm (AAA) wall inflammation and mechanical structural stress may influence AAA expansion and lead to rupture. We hypothesized a positive correlation between structural stress and fluorine-18-labeled 2-deoxy-2-fluoro-d-glucose (18F-FDG) positron emission tomography–defined inflammation. We also explored the influence of computed tomography–derived aneurysm morphology and composition, including intraluminal thrombus, on both variables. Methods and Results— Twenty-one patients (19 males) with AAAs below surgical threshold (AAA size was 4.10±0.54 cm) underwent 18F-FDG positron emission tomography and contrast-enhanced computed tomography imaging. Structural stresses were calculated using finite element analysis. The relationship between maximum aneurysm 18F-FDG standardized uptake value within aortic wall and wall structural stress, patient clinical characteristics, aneurysm morphology, and compositions was explored using a hierarchical linear mixed-effects model. On univariate analysis, local aneurysm diameter, thrombus burden, extent of calcification, and structural stress were all associated with 18F-FDG uptake (P<0.05). AAA structural stress correlated with 18F-FDG maximum standardized uptake value (slope estimate, 0.552; P<0.0001). Multivariate linear mixed-effects analysis revealed an important interaction between structural stress and intraluminal thrombus in relation to maximum standardized uptake value (fixed effect coefficient, 1.68 [SE, 0.10]; P<0.0001). Compared with other factors, structural stress was the best predictor of inflammation (receiver-operating characteristic curve area under the curve =0.59), with higher accuracy seen in regions with high thrombus burden (area under the curve =0.80). Regions with both high thrombus burden and high structural stress had higher 18F-FDG maximum standardized uptake value compared with regions with high thrombus burdens but low stress (median [interquartile range], 1.93 [1

  11. Double Endoscopic Intraluminal Operation (DEILO) for Early Gastric Cancer: Outcome of Novel Procedure for Endoscopic Submucosal Dissection.

    PubMed

    Ogata, Kyoichi; Yanai, Mitsuhiro; Kuriyama, Kengo; Suzuki, Masaki; Yanoma, Toru; Kimura, Akiharu; Kogure, Norimichi; Toyomasu, Yoshitaka; Ohno, Tetsuro; Mochiki, Erito; Kuwano, Hiroyuki

    2017-01-01

    Endoscopic submucosal dissection (ESD) has been used to treat patients with early gastric cancer (EGC). Although several endoscopic devices have been developed to ensure easy and safe ESD, this technique still requires an experienced, highly skilled endoscopist, as it is performed through a single gastroscope, thus requiring one-handed surgical techniques. To overcome these limitations, many ESD procedures with counter-traction have been developed, such as the double scope, double channel scope, clip with line, magnetic anchor, percutaneous traction and external grasping forceps methods. We devised a double endoscopic intraluminal operation (DEILO). Two endoscopes were simultaneously inserted into the stomach. One endoscope was used to lift the lesion, and the other was used to excise the lesion. The DEILO procedure was performed on 122 cases of EGC. In this article, we report the efficacy and safety of DEILO in patients with EGC.

  12. 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.

  13. The effects of caerulein and a meal stimulus on gallbladder intraluminal pressure and bile flow in the pig.

    PubMed

    Mitchenere, P; Adrian, T E; Hobbs, K E; Bloom, S R

    1981-03-01

    The intraluminal gallbladder pressure has been measured in a conscious unsedated pig model by the use of a radiotelemetry pressure capsule. A loop fistula was incorporated to measure bile output simultaneously. Mean fasting intraluminal gallbladder pressure was found to be 15 +/- 4 mmHg above atmospheric pressure, and mean fasting bile output 7.5 +/- 0.8 ml/10 min. Following intravenous caerulein pressure peaked at 2 min with a mean rise of 17 +/- 3 mmHg above basal (P less than 0.005). Bile output was increased for 30 min following caerulein with a total mean increase for this period of 13.5 +/- 2.2 ml (P less than 0.005). Gallbladder pressure rose significantly 5 min after commencing a meal by 6.0 +/- 1.9 mmHg (P less than 0.025) reaching a peak pressure 65 min after the meal with a mean rise of 14.8 +/- 2.3 mmHg (P less than 0.005). Bile output was significantly increased for 50 min following the ingestion of food. The total increments above basal values for bile output being 15.9 +/- 2.7 ml (P less than 0.005) in the first 30 min post-prandially and 1.6 +/- 2.4 ml (P less than 0.005) in the 30--60 min period. This model re-emphasizes the rapidity of the hormonal response and may be valuable for further studies on the physiology of post-prandial gallbladder emptying.

  14. 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.

  15. Multiple Cross Displacement Amplification Combined with Gold Nanoparticle-Based Lateral Flow Biosensor for Detection of Vibrio parahaemolyticus

    PubMed Central

    Wang, Yi; Li, Hui; Li, Dongxun; Li, Kewei; Wang, Yan; Xu, Jianguo; Ye, Changyun

    2016-01-01

    Vibrio parahaemolyticus (V. parahaemolyticus) is a marine seafood-borne pathogen causing severe illnesses in humans and aquatic animals. In the present study, multiple cross displacement amplification was combined with a lateral flow biosensor (MCDA-LFB) to detect the toxR gene of V. parahaemolyticus in DNA extracts from pure cultures and spiked oyster homogenates. Amplification was carried out at a constant temperature (62°C) for only 30 min, and amplification products were directly applied to the biosensor. The entire process, including oyster homogenate processing (30 min), isothermal amplification (30 min) and results indicating (∼2 min), could be completed within 65 min. Amplification product was detectable from as little as 10 fg of pure V. parahaemolyticus DNA and from approximately 4.2 × 102 CFU in 1 mL of oyster homogenate. No cross-reaction with other Vibrio species and with non-Vibrio species was observed. Therefore, the MCDA-LFB method established in the current report is suitable for the rapid screening of V. parahaemolyticus in clinical, food, and environmental samples. PMID:28066368

  16. Multiple Cross Displacement Amplification Combined with Gold Nanoparticle-Based Lateral Flow Biosensor for Detection of Vibrio parahaemolyticus.

    PubMed

    Wang, Yi; Li, Hui; Li, Dongxun; Li, Kewei; Wang, Yan; Xu, Jianguo; Ye, Changyun

    2016-01-01

    Vibrio parahaemolyticus (V. parahaemolyticus) is a marine seafood-borne pathogen causing severe illnesses in humans and aquatic animals. In the present study, multiple cross displacement amplification was combined with a lateral flow biosensor (MCDA-LFB) to detect the toxR gene of V. parahaemolyticus in DNA extracts from pure cultures and spiked oyster homogenates. Amplification was carried out at a constant temperature (62°C) for only 30 min, and amplification products were directly applied to the biosensor. The entire process, including oyster homogenate processing (30 min), isothermal amplification (30 min) and results indicating (∼2 min), could be completed within 65 min. Amplification product was detectable from as little as 10 fg of pure V. parahaemolyticus DNA and from approximately 4.2 × 10(2) CFU in 1 mL of oyster homogenate. No cross-reaction with other Vibrio species and with non-Vibrio species was observed. Therefore, the MCDA-LFB method established in the current report is suitable for the rapid screening of V. parahaemolyticus in clinical, food, and environmental samples.

  17. 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.

  18. X-ray solution scattering combined with computation characterizing protein folds and multiple conformational states : computation and application.

    SciTech Connect

    Yang, S.; Park, S.; Makowski, L.; Roux, B.

    2009-02-01

    Small angle X-ray scattering (SAXS) is an increasingly powerful technique to characterize the structure of biomolecules in solution. We present a computational method for accurately and efficiently computing the solution scattering curve from a protein with dynamical fluctuations. The method is built upon a coarse-grained (CG) representation of the protein. This CG approach takes advantage of the low-resolution character of solution scattering. It allows rapid determination of the scattering pattern from conformations extracted from CG simulations to obtain scattering characterization of the protein conformational landscapes. Important elements incorporated in the method include an effective residue-based structure factor for each amino acid, an explicit treatment of the hydration layer at the surface of the protein, and an ensemble average of scattering from all accessible conformations to account for macromolecular flexibility. The CG model is calibrated and illustrated to accurately reproduce the experimental scattering curve of Hen egg white lysozyme. We then illustrate the computational method by calculating the solution scattering pattern of several representative protein folds and multiple conformational states. The results suggest that solution scattering data, when combined with a reliable computational method, have great potential for a better structural description of multi-domain complexes in different functional states, and for recognizing structural folds when sequence similarity to a protein of known structure is low. Possible applications of the method are discussed.

  19. 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.

  20. 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.

  1. Multiple nanoemulsion system for an oral combinational delivery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation

    PubMed Central

    Pangeni, Rudra; Choi, Sang Won; Jeon, Ok-Cheol; Byun, Youngro; Park, Jin Woo

    2016-01-01

    Oxaliplatin (OXA) is a third-generation cisplatin analog that has been approved as first-line chemotherapy in combination with 5-fluorouracil (5-FU) for the treatment of resectable and advanced colorectal cancer. However, the therapeutic efficacy of oral OXA and 5-FU is limited by their low bioavailability due to poor membrane permeability. The aim of the present study was to develop an oral delivery system for OXA and 5-FU. We constructed an ion-pairing complex of OXA with a deoxycholic acid derivative (Nα-deoxycholyl-l-lysyl-methylester, DCK) (OXA/DCK) as a permeation enhancer. Next, we prepared multiple water-in-oil-in-water nanoemulsions incorporating OXA/DCK and 5-FU to enhance their oral absorption. To evaluate their membrane permeability, we assessed in vitro permeabilities of OXA/DCK and 5-FU through an artificial intestinal membrane and Caco-2 cell monolayer. Finally, oral bioavailability in rats and tumor growth inhibition in the colorectal adenocarcinoma cell (CT26)-bearing mouse model were investigated after oral administration of nanoemulsion containing OXA/DCK and 5-FU. The droplet size of the optimized nanoemulsion was 20.3±0.22 nm with a zeta potential of −4.65±1.68 mV. In vitro permeabilities of OXA/DCK and 5-FU from the nanoemulsion through a Caco-2 cell monolayer were 4.80- and 4.30-fold greater than those of OXA and 5-FU, respectively. The oral absorption of OXA/DCK and 5-FU from the nanoemulsion also increased significantly, and the resulting oral bioavailability values of OXA/DCK and 5-FU in the nanoemulsive system were 9.19- and 1.39-fold higher than those of free OXA and 5-FU, respectively. Furthermore, tumor growth in CT26 tumor-bearing mice given the oral OXA/DCK- and 5-FU-loaded nanoemulsion was maximally inhibited by 73.9%, 48.5%, and 38.1%, compared with tumor volumes in the control group and the oral OXA and 5-FU groups, respectively. These findings demonstrate the therapeutic potential of a nanoemulsion incorporating OXA/DCK and

  2. 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

  3. Robust Grape Cluster Detection in a Vineyard by Combining the AdaBoost Framework and Multiple Color Components

    PubMed Central

    Luo, Lufeng; Tang, Yunchao; Zou, Xiangjun; Wang, Chenglin; Zhang, Po; Feng, Wenxian

    2016-01-01

    The automatic fruit detection and precision picking in unstructured environments was always a difficult and frontline problem in the harvesting robots field. To realize the accurate identification of grape clusters in a vineyard, an approach for the automatic detection of ripe grape by combining the AdaBoost framework and multiple color components was developed by using a simple vision sensor. This approach mainly included three steps: (1) the dataset of classifier training samples was obtained by capturing the images from grape planting scenes using a color digital camera, extracting the effective color components for grape clusters, and then constructing the corresponding linear classification models using the threshold method; (2) based on these linear models and the dataset, a strong classifier was constructed by using the AdaBoost framework; and (3) all the pixels of the captured images were classified by the strong classifier, the noise was eliminated by the region threshold method and morphological filtering, and the grape clusters were finally marked using the enclosing rectangle method. Nine hundred testing samples were used to verify the constructed strong classifier, and the classification accuracy reached up to 96.56%, higher than other linear classification models. Moreover, 200 images captured under three different illuminations in the vineyard were selected as the testing images on which the proposed approach was applied, and the average detection rate was as high as 93.74%. The experimental results show that the approach can partly restrain the influence of the complex background such as the weather condition, leaves and changing illumination. PMID:27973409

  4. Blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration for patients with multiple organ dysfunction syndrome

    PubMed Central

    Liu, Lu-yi; Zhu, Yong-jian; Li, Xiao-li; Liang, Ya-feng; Liang, Zuo-peng; Xia, Yong-hong

    2012-01-01

    BACKGROUND: Blood hemoperfusion with resin adsorption can clean larger molecules that exceed the molecular weight cutoff of combined continuous veno-venous hemofiltration (CVVH). Hence blood hemoperfusion with resin adsorption combined CVVH (HP+CVVH) has higher ability of mediator clearance, and can improve clinical outcomes in theory. This study aimed to investigate the effect of blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration (HP+CVVH) on plasm cytokines like TNF-α, IL-1β, IL-6, cellular immunity and prognosis in patients with multiple organ dysfunction syndrome (MODS). METHODS: This was a prospective, randomized clinical trial. A total of 30 patients who had been diagnosed with MODS were enrolled in this study. Patients were randomly allocated to routine treatment+HP+CVVH group (treatment group) and routine treatment+only CVVH group (control group). In the treatment group, patients received blood hemoperfusion with resin adsorption for 2 hours, and then received CVVH for 10 hours every day. In the control group, patients received CVVH for 12 hours only every day. The patients in the two groups received blood purification therapy for three days. The plasma of patients in the treatment group was obtained at 0, 2, 12, 24, 26, 36, 48, 50, 60 hours, 5th day, 7th day and 10th day, respectively. The plasma of patients in the control group was obtained at 0, 12, 24, 36, 48, 60 hours, 5th day, 7th day and 10th day, respectively. APACHE II score, T-lymphocytes subpopulations, blood lactate acid concentration, heart rate, breathing rate, and oxygenation index were observed. RESULTS: Plasma cytokines like TNF-α, IL-1β, IL-6 decreased markedly after HP (P<0.01); T-lymphocytes subpopulations CD3+, CD4+, CD8+, CD4+/CD8+ increased after HP+CVVH or only CVVH. The plasma concentrations of TNF-α, IL-1β and IL-6 in the two groups were not markedly different at 12, 36, and 50 hours. But on the 5th day, the plasma concentrations of TNF

  5. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma

    PubMed Central

    Ocio, Enrique M.; Vilanova, David; Atadja, Peter; Maiso, Patricia; Crusoe, Edvan; Fernández-Lázaro, Diego; Garayoa, Mercedes; San-Segundo, Laura; Hernández-Iglesias, Teresa; de Álava, Enrique; Shao, Wenlin; Yao, Yung-Mae; Pandiella, Atanasio; San-Miguel, Jesús F.

    2010-01-01

    Background Combinations of drug treatments based on bortezomib or lenalidomide plus steroids have resulted in very high response rates in multiple myeloma. However, most patients still relapse, indicating the need for novel combination partners to increase duration of response or to treat relapsed disease. We explored the antimyeloma activity of triple combinations of these well-established schemes with panobinostat, a novel deacetylase inhibitor with a multi-targeted profile. Design and Methods The activity of these combinations was explored in vitro in cell lines by using MTT and annex-in V, ex vivo by flow cytometry, and in vivo using two different murine models of human myeloma: one bearing a subcutaneous plasmacytoma and another with a disseminated myeloma. Moreover, gene expression profiling and immunohistochemical studies were performed. Results The addition of panobinostat (LBH589) to dexamethasone and either bortezomib or lenalidomide resulted in clear potentiation in multiple myeloma cell lines, freshly isolated plasma cells, and murine models of multiple myeloma. The quantification of the potency of these combinations by using the Chou-Talalay method showed synergistic combination indices for all of them. This effect derived from the deregulation of a cluster of genes that was completely different from the sum of genes affected by the single agents (895 and 1323 genes exclusively deregulated by panobinostat and dexamethasone plus bortezomib or lenalidomide, respectively). Functional experiments, such as annexin V staining, cell cycle analysis, and immunohistochemical studies also supported this potentiation. Anti-myeloma efficacy was confirmed in an extramedullary plasmacytoma model and a disseminated luciferized model, in which panobinostat also provided a marked benefit in bone disease. Conclusions The potent activity, together with the exclusive mechanistic profile, provides the rationale for the clinical evaluation of these drug combinations in

  6. 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

  7. Intimal hyperplasia following implantation of helical-centreline and straight-centreline stents in common carotid arteries in healthy pigs: influence of intraluminal flow†

    PubMed Central

    Caro, Colin Gerald; Seneviratne, Anusha; Heraty, Kevin B.; Monaco, Claudia; Burke, Martin G.; Krams, Rob; Chang, Carlos C.; Coppola, Gianfilippo; Gilson, Paul

    2013-01-01

    Intimal hyperplasia (IH) is a leading cause of obstruction of vascular interventions, including arterial stents, bypass grafts and arteriovenous grafts and fistulae. Proposals to account for arterial stent-associated IH include wall damage, low wall shear stress (WSS), disturbed flow and, although not widely recognized, wall hypoxia. The common non-planarity of arterial geometry and flow, led us to develop a bare-metal, nitinol, self-expanding stent with three-dimensional helical-centreline geometry. This was deployed in one common carotid artery of healthy pigs, with a straight-centreline, but otherwise identical (conventional) stent deployed contralaterally. Both stent types deformed the arteries, but the helical-centreline device additionally deformed them helically and caused swirling of intraluminal flow. At sacrifice, one month post stent deployment, histology revealed significantly less IH in the helical-centreline than straight-centreline stented vessels. Medial cross-sectional area was not significantly different in helical-centreline than straight-centreline stented vessels. By contrast, luminal cross-sectional area was significantly larger in helical-centreline than straight-centreline stented vessels. Mechanisms considered to account for those results include enhanced intraluminal WSS and enhanced intraluminal blood–vessel wall mass transport, including of oxygen, in the helical-centreline stented vessels. Consistent with the latter proposal, adventitial microvessel density was lower in the helical-centreline stented than straight-centreline stented vessels. PMID:24132200

  8. An integrated fluid-chemical model toward modeling the formation of intra-luminal thrombus in abdominal aortic aneurysms.

    PubMed

    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.

  9. 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.

  10. Suppression of large intraluminal bubble expansion in shock wave lithotripsy without compromising stone comminution: Refinement of reflector geometry

    NASA Astrophysics Data System (ADS)

    Zhou, Yufeng; Zhong, Pei

    2003-01-01

    Using the Hamilton model [Hamilton, J. Acoust. Soc. Am. 93, 1256-1266 (1993)], the effects of reflector geometry on the pulse profile and sequence of the shock waves produced by the original and upgraded reflector of an HM-3 lithotripter were evaluated qualitatively. Guided by this analysis, we have refined the geometry of the upgraded reflector to enhance its suppressive effect on intraluminal bubble expansion without compromising stone comminution in shock wave lithotripsy. Using the original HM-3 reflector at 20 kV, rupture of a standard vessel phantom made of cellulose hollow fiber (i.d.=0.2 mm), in which degassed water seeded with ultrasound contrast agents was circulated, was produced at the lithotripter focus after about 30 shocks. In contrast, using the upgraded reflector at 24 kV no rupture of the vessel phantom could be produced within a 20-mm diameter around the lithotripter focus even after 200 shocks. On the other hand, stone comminution was comparable between the two reflector configurations, although slightly larger fragments were produced by the upgraded reflector. After 2000 shocks, stone comminution efficiency produced by the original HM-3 reflector at 20 kV is 97.15+/-1.92% (mean+/-SD), compared to 90.35+/-1.96% produced by the upgraded reflector at 24 kV (p<0.02). All together, it was found that the upgraded reflector could significantly reduce the propensity for vessel rupture in shock wave lithotripsy while maintaining satisfactory stone comminution.

  11. Catheter-based high-frequency intraluminal ultrasound imaging is a powerful tool to study esophageal dysmotility patients.

    PubMed

    Santander, Cecilio; Perea, Elena; Caldas, María; Clave, Pere

    2017-01-31

    High-resolution manometry (HRM) is currently the most important diagnostic test for esophageal motility disorders, providing information on the contraction pattern of the circular muscle layer, which helps classify these esophageal motor diseases. However, with the increasing development of ultrasound, other techniques, such as high-frequency intraluminal ultrasound (HFIUS), have gained importance. This technique uses a flexible shaft with a central wire integrated into a standard endoscope, which facilitates real-time sonography. Its main utility is to provide anatomical information on the structure of the esophageal wall, including both the circular and longitudinal layers that constitute the esophageal muscularis propria. Increasing knowledge about these motility disorders has led to the hypothesis that, in addition to an abnormal contraction pattern of the circular muscle, an overall increased muscle thickness and an abnormal longitudinal muscle contraction could be added as pathophysiological factors. The increase in muscle thickness could be an important indicator of the severity of diseases, such as achalasia, distal esophageal spasm, or hypercontractile esophagus. More studies are required before definitive conclusions can be reached, but HFIUS employed simultaneously with HRM could provide a more complete and precise evaluation of these esophageal motor disorders.

  12. Intraluminal laser speckle rheology using an omni-directional viewing catheter

    PubMed Central

    Wang, Jing; Hosoda, Masaki; Tshikudi, Diane M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.

    2016-01-01

    A number of disease conditions in luminal organs are associated with alterations in tissue mechanical properties. Here, we report a new omni-directional viewing Laser Speckle Rheology (LSR) catheter for mapping the mechanical properties of luminal organs without the need for rotational motion. The LSR catheter incorporates multiple illumination fibers, an optical fiber bundle and a multi-faceted mirror to permit omni-directional viewing of the luminal wall. By retracting the catheter using a motor-drive assembly, cylindrical maps of tissue mechanical properties are reconstructed. Evaluation conducted in a test phantom with circumferentially-varying mechanical properties demonstrates the capability of the LSR catheter for the accurate mechanical assessment of luminal organs. PMID:28101407

  13. Acceleration of canonical molecular dynamics simulations using macroscopic expansion of the fast multipole method combined with the multiple timestep integrator algorithm

    NASA Astrophysics Data System (ADS)

    Kawata, Masaaki; Mikami, Masuhiro

    A canonical molecular dynamics (MD) simulation was accelerated by using an efficient implementation of the multiple timestep integrator algorithm combined with the periodic fast multiple method (MEFMM) for both Coulombic and van der Waals interactions. Although a significant reduction in computational cost has been obtained previously by using the integrated method, in which the MEFMM was used only to calculate Coulombic interactions (Kawata, M., and Mikami, M., 2000, J. Comput. Chem., in press), the extension of this method to include van der Waals interactions yielded further acceleration of the overall MD calculation by a factor of about two. Compared with conventional methods, such as the velocity-Verlet algorithm combined with the Ewald method (timestep of 0.25fs), the speedup by using the extended integrated method amounted to a factor of 500 for a 100 ps simulation. Therefore, the extended method reduces substantially the computational effort of large scale MD simulations.

  14. Complete sequence of human mitochondrial DNA obtained by combining multiple displacement amplification and next-generation sequencing on a single oocyte.

    PubMed

    Ancora, Massimo; Orsini, Massimiliano; Colosimo, Alessia; Marcacci, Maurilia; Russo, Valentina; De Santo, Maria; D'Aurora, Marco; Stuppia, Liborio; Barboni, Barbara; Cammà, Cesare; Gatta, Valentina

    2017-03-01

    Mitochondrial DNA (mtDNA) plays a key role in the development of a competent oocyte. In this study, the complete mtDNA sequence obtained for the first time by multiple displacement amplification approach in combination with next-generation sequencing from a single human oocyte is reported (GenBank accession no. KT364276). The analysis of oocyte mitochondrial mutations could provide a better understanding of the genetic variants correlated with the oocyte quality.

  15. 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…

  16. Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade.

    PubMed

    Phillipson, Mia; Heit, Bryan; Colarusso, Pina; Liu, Lixin; Ballantyne, Christie M; Kubes, Paul

    2006-11-27

    The prevailing view is that the beta2-integrins Mac-1 (alphaMbeta2, CD11b/CD18) and LFA-1 (alphaLbeta2, CD11a/CD18) serve similar biological functions, namely adhesion, in the leukocyte recruitment cascade. Using real-time and time-lapse intravital video-microscopy and confocal microscopy within inflamed microvessels, we systematically evaluated the function of Mac-1 and LFA-1 in the recruitment paradigm. The chemokine macrophage inflammatory protein-2 induced equivalent amounts of adhesion in wild-type and Mac-1-/- mice but very little adhesion in LFA-1-/- mice. Time-lapse video-microscopy within the postcapillary venules revealed that immediately upon adhesion, there is significant intraluminal crawling of all neutrophils to distant emigration sites in wild-type mice. In dramatic contrast, very few Mac-1-/- neutrophils crawled with a 10-fold decrease in displacement and a 95% reduction in velocity. Therefore, Mac-1-/- neutrophils initiated transmigration closer to the initial site of adhesion, which in turn led to delayed transmigration due to movement through nonoptimal emigration sites. Interestingly, the few LFA-1-/- cells that did adhere crawled similarly to wild-type neutrophils. Intercellular adhesion molecule-1 but not intercellular adhesion molecule-2 mediated the Mac-1-dependent crawling. These in vivo results clearly delineate two fundamentally different molecular mechanisms for LFA-1 and Mac-1 in vivo, i.e., LFA-1-dependent adhesion followed by Mac-1-dependent crawling, and both steps ultimately contribute to efficient emigration out of the vasculature.

  17. Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade

    PubMed Central

    Phillipson, Mia; Heit, Bryan; Colarusso, Pina; Liu, Lixin; Ballantyne, Christie M.; Kubes, Paul

    2006-01-01

    The prevailing view is that the β2-integrins Mac-1 (αMβ2, CD11b/CD18) and LFA-1 (αLβ2, CD11a/CD18) serve similar biological functions, namely adhesion, in the leukocyte recruitment cascade. Using real-time and time-lapse intravital video-microscopy and confocal microscopy within inflamed microvessels, we systematically evaluated the function of Mac-1 and LFA-1 in the recruitment paradigm. The chemokine macrophage inflammatory protein-2 induced equivalent amounts of adhesion in wild-type and Mac-1−/− mice but very little adhesion in LFA-1−/− mice. Time-lapse video-microscopy within the postcapillary venules revealed that immediately upon adhesion, there is significant intraluminal crawling of all neutrophils to distant emigration sites in wild-type mice. In dramatic contrast, very few Mac-1−/− neutrophils crawled with a 10-fold decrease in displacement and a 95% reduction in velocity. Therefore, Mac-1−/− neutrophils initiated transmigration closer to the initial site of adhesion, which in turn led to delayed transmigration due to movement through nonoptimal emigration sites. Interestingly, the few LFA-1−/− cells that did adhere crawled similarly to wild-type neutrophils. Intercellular adhesion molecule-1 but not intercellular adhesion molecule-2 mediated the Mac-1–dependent crawling. These in vivo results clearly delineate two fundamentally different molecular mechanisms for LFA-1 and Mac-1 in vivo, i.e., LFA-1–dependent adhesion followed by Mac-1–dependent crawling, and both steps ultimately contribute to efficient emigration out of the vasculature. PMID:17116736

  18. 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.

  19. Combination of multiple model population analysis and mid-infrared technology for the estimation of copper content in Tegillarca granosa

    NASA Astrophysics Data System (ADS)

    Hu, Meng-Han; Chen, Xiao-Jing; Ye, Peng-Chao; Chen, Xi; Shi, Yi-Jian; Zhai, Guang-Tao; Yang, Xiao-Kang

    2016-11-01

    The aim of this study was to use mid-infrared spectroscopy coupled with multiple model population analysis based on Monte Carlo-uninformative variable elimination for rapidly estimating the copper content of Tegillarca granosa. Copper-specific wavelengths were first extracted from the whole spectra, and subsequently, a least square-support vector machine was used to develop the prediction models. Compared with the prediction model based on full wavelengths, models that used 100 multiple MC-UVE selected wavelengths without and with bin operation showed comparable performances with Rp (root mean square error of Prediction) of 0.97 (14.60 mg/kg) and 0.94 (20.85 mg/kg) versus 0.96 (17.27 mg/kg), as well as ratio of percent deviation (number of wavelength) of 2.77 (407) and 1.84 (45) versus 2.32 (1762). The obtained results demonstrated that the mid-infrared technique could be used for estimating copper content in T. granosa. In addition, the proposed multiple model population analysis can eliminate uninformative, weakly informative and interfering wavelengths effectively, that substantially reduced the model complexity and computation time.

  20. 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.

  1. Effect of mefloquine administered orally at single, multiple, or combined with artemether, artesunate, or praziquantel in treatment of mice infected with Schistosoma japonicum.

    PubMed

    Xiao, Shu-hua; Mei, Jing-yan; Jiao, Pei-ying

    2011-02-01

    The purpose of the study is to explore the efficacy of mefloquine administered orally at single, multiple doses, or in combination with artesuante, artemether, or praziquantel in mouse--Schistosoma japonicum model. A total of 205 mice were divided into 4 batches and each batch of mice was infected percutaneously with 40 S. japonicum cercariae for 35 days. The infected mice were treated orally with mefloquine at single doses, multiple daily doses, or combined with artesunate, artemether, or praziquantel, while infected but untreated mice served as control. All treated animals were killed 4 weeks post-treatment for assessment of effect. When infected mice were treated orally with mefloquine at single or multiple daily doses under the same total dose levels, the tendency to decrease the efficacy was seen. Particularly, when a lower single dose of 100 mg/kg was divided equally into five daily doses of 20 mg/kg, the efficacy decreased statistically significant (P<0.05), i.e., the total worm and female worm reductions of 67.9% and 73.4% decreased to 31.3% and 30.3%, respectively. In infected mice treated with mefloquine or artesuante at a single dose of 100 mg/kg, a moderate effect against schistosomes was observed. No further significant reduction of total and female worm burdens was seen, when the two drugs combined together at the same dose level. On the other hand, administration of mefloquine combined with artesunate at single dose of 50 mg/kg, which exhibited no effect against schistosomes, resulted in significant reduction of total and female worm burdens in comparison with the groups treated with mefloquine and artesunate alone at the same dose level. Similar results were observed in treatment of infected mice with mefloquine in combination with artemether at the smaller dose of 50 mg/kg. The total worm burden was significantly lower than that of control and the female worm burden was also significant lower than that of groups treated with mefloquine and

  2. A modification of intraluminal middle cerebral artery occlusion/reperfusion model for ischemic stroke with laser Doppler flowmetry guidance in mice

    PubMed Central

    Cai, Qiang; Xu, Gang; Liu, Junhui; Wang, Long; Deng, Gang; Liu, Jun; Chen, Zhibiao

    2016-01-01

    Stroke is one of the common causes of death and disability in the world. The intraluminal middle cerebral artery occlusion/reperfusion (MCAO/R) model is a “gold standard” in surgical ischemic stroke models. Here, we optimized the procedure of this model by ligating on external carotid artery (ECA) stump and two ligatures prepared on internal carotid artery, which could improve the success and survival rate in mice. The results show that ECA approach was superior to common carotid artery approach. Meanwhile, we found that the exposure of pterygopalatine artery was not an essential step for MCAO/R model in mice. PMID:27843320

  3. [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.

  4. Combining Genes from Multiple Phages for Improved Cell Lysis and DNA Transfer from Escherichia coli to Bacillus subtilis

    PubMed Central

    Juhas, Mario; Wong, Christine; Ajioka, James W.

    2016-01-01

    The ability to efficiently and reliably transfer genetic circuits between the key synthetic biology chassis, such as Escherichia coli and Bacillus subtilis, constitutes one of the major hurdles of the rational genome engineering. Using lambda Red recombineering we integrated the thermosensitive lambda repressor and the lysis genes of several bacteriophages into the E. coli chromosome. The lysis of the engineered autolytic cells is inducible by a simple temperature shift. We improved the lysis efficiency by introducing different combinations of lysis genes from bacteriophages lambda, ΦX174 and MS2 under the control of the thermosensitive lambda repressor into the E. coli chromosome. We tested the engineered autolytic cells by transferring plasmid and bacterial artificial chromosome (BAC)-borne genetic circuits from E. coli to B. subtilis. Our engineered system combines benefits of the two main synthetic biology chassis, E. coli and B. subtilis, and allows reliable and efficient transfer of DNA edited in E. coli into B. subtilis. PMID:27798678

  5. Repeated dose liver micronucleus assay using adult mice with multiple genotoxicity assays concurrently performed as a combination test.

    PubMed

    Hagio, Soichiro; Furukawa, Satoshi; Abe, Masayoshi; Kuroda, Yusuke; Hayashi, Seigo; Ogawa, Izumi

    2014-06-01

    Recently, the liver micronucleus (MN) assay using young adult rats with repeated administrations has been investigated by employing a new method without partial hepatectomy or in situcollagenase perfusion as the repeated dose liver MN (RDLMN) assay by Narumi et al. (2012). In our study, in order to investigate the possibility of the RDLMN assay using young adult mice instead of rats and the feasibility of employing some genotoxicity assays along with the RDLMN assay as a combination test, two genotoxic carcinogens (N,N-diethylnitrosoamine (DEN) and cisplatin (CIS)) and a nongenotoxic carcinogen (phenobarbital sodium (PHE)) were administered to mice for 15 or 29 days. Then, the liver MN assay, peripheral blood (PB) MN assay and comet assay using the liver and kidney were concurrently performed as a combination test. DEN showed positive responses to all endpoints except MN induction in PB after 15 days of repeat administration. A cross-linking agent, CIS, showed MN induction in liver after 29 days of repeat administration, and in PB after 15 and 29 days of repeat administration, although the comet assay yielded negative responses for both organs at both sampling times. PHE yielded negative responses for all endpoints. In conclusion, it is suggested that the RDLMN assay using mice is a feasible method to be integrated into the general repeated toxicity test along with the combination assays, i.e., comet assay or PB MN assay, which would help in risk assessment for carcinogenicity by comparing the results of combination assays with each other.

  6. Gene-based multiple regression association testing for combined examination of common and low frequency variants in quantitative trait analysis.

    PubMed

    Yoo, Yun Joo; Sun, Lei; Bull, Shelley B

    2013-01-01

    Multi-marker methods for genetic association analysis can be performed for common and low frequency SNPs to improve power. Regression models are an intuitive way to formulate multi-marker tests. In previous studies we evaluated regression-based multi-marker tests for common SNPs, and through identification of bins consisting of correlated SNPs, developed a multi-bin linear combination (MLC) test that is a compromise between a 1 df linear combination test and a multi-df global test. Bins of SNPs in high linkage disequilibrium (LD) are identified, and a linear combination of individual SNP statistics is constructed within each bin. Then association with the phenotype is represented by an overall statistic with df as many or few as the number of bins. In this report we evaluate multi-marker tests for SNPs that occur at low frequencies. There are many linear and quadratic multi-marker tests that are suitable for common or low frequency variant analysis. We compared the performance of the MLC tests with various linear and quadratic statistics in joint or marginal regressions. For these comparisons, we performed a simulation study of genotypes and quantitative traits for 85 genes with many low frequency SNPs based on HapMap Phase III. We compared the tests using (1) set of all SNPs in a gene, (2) set of common SNPs in a gene (MAF ≥ 5%), (3) set of low frequency SNPs (1% ≤ MAF < 5%). For different trait models based on low frequency causal SNPs, we found that combined analysis using all SNPs including common and low frequency SNPs is a good and robust choice whereas using common SNPs alone or low frequency SNP alone can lose power. MLC tests performed well in combined analysis except where two low frequency causal SNPs with opposing effects are positively correlated. Overall, across different sets of analysis, the joint regression Wald test showed consistently good performance whereas other statistics including the ones based on marginal regression had lower power for

  7. 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).

  8. 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

  9. Combining Phylogeography with Distribution Modeling: Multiple Pleistocene Range Expansions in a Parthenogenetic Gecko from the Australian Arid Zone

    PubMed Central

    Strasburg, Jared L.; Kearney, Michael; Moritz, Craig; Templeton, Alan R.

    2007-01-01

    Phylogenetic and geographic evidence suggest that many parthenogenetic organisms have evolved recently and have spread rapidly. These patterns play a critical role in our understanding of the relative merits of sexual versus asexual reproductive modes, yet their interpretation is often hampered by a lack of detail. Here we present a detailed phylogeographic study of a vertebrate parthenogen, the Australian gecko Heteronotia binoei, in combination with statistical and biophysical modeling of its distribution during the last glacial maximum. Parthenogenetic H. binoei occur in the Australian arid zone and have the widest range of any known vertebrate parthenogen. They are broadly sympatric with their sexual counterparts, from which they arose via hybridization. We have applied nested clade phylogeographic, effective migration, and mismatch distribution analyses to mitochondrial DNA (mtDNA) sequences obtained for 319 individuals sampled throughout the known geographic ranges of two parthenogenetic mitochondrial lineages. These analyses provide strong evidence for past range expansion events from west to east across the arid zone, and for continuing eastward range expansion. Parthenogen formation and range expansion events date to the late Pleistocene, with one lineage expanding from the northwest of its present range around 240,000 years ago and the second lineage expanding from the far west around 70,000 years ago. Statistical and biophysical distribution models support these inferences of recent range expansion, with suitable climatic conditions during the last glacial maximum most likely limited to parts of the arid zone north and west of much of the current ranges of these lineages. Combination of phylogeographic analyses and distribution modeling allowed considerably stronger inferences of the history of this complex than either would in isolation, illustrating the power of combining complementary analytical approaches. PMID:17712408

  10. Immune-regulatory transcriptional responses in multiple organs of Atlantic salmon after tributyltin exposure, alone or in combination with forskolin.

    PubMed

    Pavlikova, Nela; Arukwe, Augustine

    2011-01-01

    Tributyltin (TBT) is a widespread marine pollutant that influences physiological conditions of fish and other aquatic organisms. In addition to effects on reproduction, the immune system has been proposed as a possible target for TBT effects. In the present study, the effects of TBT exposure were examined on the expression of genes involved in immune system compentence in liver and head kidney of Atlantic salmon, in the presence and absence of a second-messenger activator (forskolin). Juvenile salmon were force-fed a diet containing TBT (0-solvent control, 0.1, 1, or 10 mg/kg fish) for 72 h. Consequently, fish from the control group and 10-mg/kg TBT group were exposed to the adenylate cyclase (AC) activator forskolin (200 μg/L) for 2 or 4 h. Forskolin was selected for this study because it is known to exhibit potent immune system enhancement by activating macrophages and lymphocytes. After sacrifice, liver and head kidney were sampled and transcript changes for interleukin (IL)-1β, IL-10, transforming growth factor (TGF) β, interferon (INF) α, INFγ, tumor necrosis factor (TNF) α, Mx3, and insulin-like growth factor (IGF)-1 were determined in both tissues by quantitative polymerase chain reaction (qPCR) using gene-specific primers. TBT, when given alone and also in combination with forskolin, decreased IL-1β, TNFα, IFNγ, IFNα, Mx3, and IGF-1 gene expression. In contrast, IL-10 and TGFβ transcripts were increased after TBT exposure alone and also in combination with forskolin. Generally, these effects were largely dependent on TBT dose and time of exposure when given in combination with forskolin. Overall, our findings suggest a possible immunomodulatory effect of TBT, possibly involving cAMP activation.

  11. 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.

  12. An upper tropospheric and stratospheric water vapor data set produced by combining records from multiple satellite platforms

    NASA Astrophysics Data System (ADS)

    Rosenlof, K. H.; Davis, S. M.; Anderson, J.; Hurst, D. F.; Oltmans, S. J.

    2010-12-01

    Vertical profiles of humidity from the upper troposphere to stratosphere have been retrieved from several different limb sounding and solar occultation satellite instruments since the 1980’s. Instruments retrieving water vapor include the SAGE and POAM instruments, UARS MLS, UARS HALOE, and more recently, ACE-FTS and Aura MLS. Here, we present ongoing work aimed at combining these measurements into a geographically gridded data set that can be used for quantifying variability and long-term changes in water vapor, and also for assessing the radiative impact of changes in upper tropospheric and stratospheric humidity. At the present time, we have combined the newest V20 HALOE retrieval and the MLS version 2 retrieval and have compared tropical water with that inferred from the newest NCEP reanalysis, the Climate Forecast System Reanalysis. Results from that comparison, comparisons with the Boulder water vapor sonde data set, and discussion of the radiative and climate impact of trends and decadal variability in UTLS water vapor will be presented.

  13. 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.

  14. 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

  15. Combining Crowding Estimation in Objective and Decision Space With Multiple Selection and Search Strategies for Multi-Objective Evolutionary Optimization.

    PubMed

    Xia, Hu; Zhuang, Jian; Yu, Dehong

    2014-03-01

    Many multi-objective evolutionary algorithms (MOEAs) have been successful in approximating the Pareto Front. However, well-distributed solutions in the objective and decision spaces are still required in many real-life applications. In this paper, a novel MOEA is proposed to this problem. Distinct from other MOEAs, the proposed algorithm suggests a framework, which includes two crowding estimation methods, multiple selection methods for mating and search strategies for variation, to improve the MOEA' s searching ability, and the diversity of its solutions. The algorithm emphasizes the importance of using the decision space and the objective space diversities. The objective space crowding and decision space crowding distances are designed using different ideas. To produce new individuals, three different types of mating selections and their respective search strategies are constructed for the main population and the two sparse populations, with the help of the two crowding measurements. Finally, based on the experimental tests on 17 unconstrained multi-objective optimization problems, the proposed algorithm is demonstrated to have better results compared to several state-of-the-art MOEAs. A detailed analysis on the effectiveness and robustness of the framework is also presented.

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

    PubMed Central

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

    2013-01-01

    Purpose: Many approaches have been proposed to segment high uptake objects in 18F-fluoro-deoxy-glucose positron emission tomography images but none provides consistent performance across the large variety of imaging situations. This study investigates the use of two methods of combining individual segmentation methods to reduce the impact of inconsistent performance of the individual methods: simple majority voting and probabilistic estimation. Methods: The National Electrical Manufacturers Association image quality phantom containing five glass spheres with diameters 13–37 mm and two irregularly shaped volumes (16 and 32 cc) formed by deforming high-density polyethylene bottles in a hot water bath were filled with 18-fluoro-deoxyglucose and iodine contrast agent. Repeated 5-min positron emission tomography (PET) images were acquired at 4:1 and 8:1 object-to-background contrasts for spherical objects and 4.5:1 and 9:1 for irregular objects. Five individual methods were used to segment each object: 40% thresholding, adaptive thresholding, k-means clustering, seeded region-growing, and a gradient based method. Volumes were combined using a majority vote (MJV) or Simultaneous Truth And Performance Level Estimate (STAPLE) method. Accuracy of segmentations relative to CT ground truth volumes were assessed using the Dice similarity coefficient (DSC) and the symmetric mean absolute surface distances (SMASDs). Results: MJV had median DSC values of 0.886 and 0.875; and SMASD of 0.52 and 0.71 mm for spheres and irregular shapes, respectively. STAPLE provided similar results with median DSC of 0.886 and 0.871; and median SMASD of 0.50 and 0.72 mm for spheres and irregular shapes, respectively. STAPLE had significantly higher DSC and lower SMASD values than MJV for spheres (DSC, p < 0.0001; SMASD, p = 0.0101) but MJV had significantly higher DSC and lower SMASD values compared to STAPLE for irregular shapes (DSC, p < 0.0001; SMASD, p = 0.0027). DSC was not significantly

  17. Combined Orthodontic-surgical Treatment for Skeletal Class III Malocclusion with Multiple Impacted Permanent and Supernumerary Teeth: Case Report

    PubMed Central

    Xue, Dai Juan and Feng

    2014-01-01

    In this report we describe a combined orthodontic and surgical treatment for a 14-year-old boy with severe skeletal class III deformity and dental problem. His upper posterior primary teeth in the left side were over-retained and 6 maxillary teeth (bilateral central incisors and canines, left first and second premolars) were impacted, together with 5 supernumerary teeth in both arches. The treatment protocol involved extraction of all the supernumerary and deciduous teeth, surgical exposure and orthodontic traction of the impacted teeth, a bimaxillary orthognathic approach including Lefort I osteotomy. Bilateral sagittal split ramus osteotomy (BSSRO) and genioplasty was performed to correct skeletal problem. After treatment, all of the impacted teeth were brought to proper alignment in the maxillary arch. A satisfied profile and good posterior occlusion was achieved. Treatment mechanics and consideration during different stages are discussed. PMID:24893948

  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. PMID:27648171

  19. 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.

  20. Multiple methods of surgical treatment combined with primary IOL implantation on traumatic lens subluxation/dislocation in patients with secondary glaucoma

    PubMed Central

    Wang, Rui; Bi, Chun-Chao; Lei, Chun-Ling; Sun, Wen-Tao; Wang, Shan-Shan; Dong, Xiao-Juan

    2014-01-01

    AIM To describe clinical findings and complications from cases of traumatic lens subluxation/dislocation in patients with secondary glaucoma, and discuss the multiple treating methods of operation combined with primary intraocular lens (IOL) implantation. METHODS Non-comparative retrospective observational case series. Participants: 30 cases (30 eyes) of lens subluxation/dislocation in patients with secondary glaucoma were investigated which accepted the surgical treatment by author in the Ophthalmology of Xi'an No.4 Hospital from 2007 to 2011. According to the different situations of lens subluxation/dislocation, various surgical procedures were performed such as crystalline lens phacoemulsification, crystalline lens phacoemulsification combined anterior vitrectomy, intracapsular cataract extraction combined anterior vitrectomy, lensectomy combined anterior vitrectomy though peripheral transparent cornea incision, pars plana lensectomy combined pars plana vitrectomy, and intravitreal cavity crystalline lens phacofragmentation combined pars plana vitrectomy. And whether to implement trabeculectomy depended on the different situations of secondary glaucoma. The posterior chamber intraocular lenses (PC-IOLs) were implanted in the capsular-bag or trassclerally sutured in the sulus decided by whether the capsular were present. Main outcome measures: visual acuity, intraocular pressure, the situation of intraocular lens and complications after the operations. RESULTS The follow-up time was 11-36mo (21.4±7.13). Postoperative visual acuity of all eyes were improved; 28 cases maintained IOP below 21 mm Hg; 2 cases had slightly IOL subluxation, 4 cases had slightly tilted lens optical area; 1 case had postoperative choroidal detachment; 4 cases had postoperative corneal edema more than 1wk, but eventually recovered transparent; 2 cases had mild postoperative vitreous hemorrhage, and absorbed 4wk later. There was no postoperative retinal detachment, IOL dislocation, and

  1. Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma.

    PubMed

    Shah, Nina; Li, Li; McCarty, Jessica; Kaur, Indreshpal; Yvon, Eric; Shaim, Hila; Muftuoglu, Muharrem; Liu, Enli; Orlowski, Robert Z; Cooper, Laurence; Lee, Dean; Parmar, Simrit; Cao, Kai; Sobieiski, Catherine; Saliba, Rima; Hosing, Chitra; Ahmed, Sairah; Nieto, Yago; Bashir, Qaiser; Patel, Krina; Bollard, Catherine; Qazilbash, Muzaffar; Champlin, Richard; Rezvani, Katy; Shpall, Elizabeth J

    2017-03-14

    Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m(2) on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 10(6) , 1 × 10(7) , 5 × 10(7) and 1 × 10(8) CB-NK cells/kg. Ten patients had either high-risk chromosomal changes or a history of relapsed/progressed disease. There were no infusional toxicities and no graft-versus-host disease. One patient failed to engraft due to poor autologous graft quality and was rescued with a back-up autologous graft. Overall, 10 patients achieved at least a very good partial response as their best response, including eight with near complete response or better. With a median follow-up of 21 months, four patients have progressed or relapsed, two of whom have died. CB-NK cells were detected in vivo in six patients, with an activated phenotype (NKG2D(+) /NKp30(+) ). These data warrant further development of this novel cellular therapy.

  2. 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.

  3. 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.

  4. Ultrasensitive detection of bacteria by microchip electrophoresis based on multiple-concentration approaches combining chitosan sweeping, field-amplified sample stacking, and reversed-field stacking.

    PubMed

    Wang, Zhi-Fang; Cheng, Shuang; Ge, Shu-Li; Wang, Huan; Wang, Qing-Jiang; He, Pin-Gang; Fang, Yu-Zhi

    2012-02-07

    In this paper we describe an on-chip multiple-concentration method combining chitosan (CS) sweeping, reversed-field stacking, and field-amplified sample stacking for highly efficient detection of bacteria. Escherichia coli was selected as a model bacterium to investigate the efficiency of this multiple-concentration method. CS was the most suitable sweeping agent for microchip electrophoresis, replacing the usually used cetyltrimethylammonium bromide for capillary electrophoresis. The additive taurine had a synergistic effect by enhancing the interaction between CS and the surface of the bacteria, thus improving the analysis sensitivity. All steps of the concentration method and related mechanisms are described and discussed in detail. A concentration enhancement factor of approximately 6000 was obtained using this concentration method under optimal conditions as compared to using no concentration step, and the detection limit of E. coli was 145 CFU/mL. The multiple-concentration methodology was also applied for the quantification of bacteria in surface water, and satisfactory results were achieved. The application of this methodology showed that the concentration enhancement of bacteria clearly conferred advantageous sensitivity, speed, and sample volume compared to established methods.

  5. Predicting siRNA efficacy based on multiple selective siRNA representations and their combination at score level

    NASA Astrophysics Data System (ADS)

    He, Fei; Han, Ye; Gong, Jianting; Song, Jiazhi; Wang, Han; Li, Yanwen

    2017-03-01

    Small interfering RNAs (siRNAs) may induce to targeted gene knockdown, and the gene silencing effectiveness relies on the efficacy of the siRNA. Therefore, the task of this paper is to construct an effective siRNA prediction method. In our work, we try to describe siRNA from both quantitative and qualitative aspects. For quantitative analyses, we form four groups of effective features, including nucleotide frequencies, thermodynamic stability profile, thermodynamic of siRNA-mRNA interaction, and mRNA related features, as a new mixed representation, in which thermodynamic of siRNA-mRNA interaction is introduced to siRNA efficacy prediction for the first time to our best knowledge. And then an F-score based feature selection is employed to investigate the contribution of each feature and remove the weak relevant features. Meanwhile, we encode the siRNA sequence and existed empirical design rules as a qualitative siRNA representation. These two kinds of siRNA representations are combined to predict siRNA efficacy by supported Vector Regression (SVR) at score level. The experimental results indicate that our method may select the features with powerful discriminative ability and make the two kinds of siRNA representations work at full capacity. The prediction results also demonstrate that our method can outperform other popular siRNA efficacy prediction algorithms.

  6. Hybrid approach combining multiple characterization techniques and simulations for microstructural analysis of proton exchange membrane fuel cell electrodes

    NASA Astrophysics Data System (ADS)

    Cetinbas, Firat C.; Ahluwalia, Rajesh K.; Kariuki, Nancy; De Andrade, Vincent; Fongalland, Dash; Smith, Linda; Sharman, Jonathan; Ferreira, Paulo; Rasouli, Somaye; Myers, Deborah J.

    2017-03-01

    The cost and performance of proton exchange membrane fuel cells strongly depend on the cathode electrode due to usage of expensive platinum (Pt) group metal catalyst and sluggish reaction kinetics. Development of low Pt content high performance cathodes requires comprehensive understanding of the electrode microstructure. In this study, a new approach is presented to characterize the detailed cathode electrode microstructure from nm to μm length scales by combining information from different experimental techniques. In this context, nano-scale X-ray computed tomography (nano-CT) is performed to extract the secondary pore space of the electrode. Transmission electron microscopy (TEM) is employed to determine primary C particle and Pt particle size distributions. X-ray scattering, with its ability to provide size distributions of orders of magnitude more particles than TEM, is used to confirm the TEM-determined size distributions. The number of primary pores that cannot be resolved by nano-CT is approximated using mercury intrusion porosimetry. An algorithm is developed to incorporate all these experimental data in one geometric representation. Upon validation of pore size distribution against gas adsorption and mercury intrusion porosimetry data, reconstructed ionomer size distribution is reported. In addition, transport related characteristics and effective properties are computed by performing simulations on the hybrid microstructure.

  7. Combining Multiple Hypothesis Testing with Machine Learning Increases the Statistical Power of Genome-wide Association Studies

    PubMed Central

    Mieth, Bettina; Kloft, Marius; Rodríguez, Juan Antonio; Sonnenburg, Sören; Vobruba, Robin; Morcillo-Suárez, Carlos; Farré, Xavier; Marigorta, Urko M.; Fehr, Ernst; Dickhaus, Thorsten; Blanchard, Gilles; Schunk, Daniel; Navarro, Arcadi; Müller, Klaus-Robert

    2016-01-01

    The standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008–2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0. PMID:27892471

  8. Flood fatality hazard and flood damage hazard: combining multiple hazard characteristics into meaningful maps for spatial planning

    NASA Astrophysics Data System (ADS)

    de Bruijn, K. M.; Klijn, F.; van de Pas, B.; Slager, C. T. J.

    2015-06-01

    For comprehensive flood risk management, accurate information on flood hazards is crucial. While in the past an estimate of potential flood consequences in large areas was often sufficient to make decisions on flood protection, there is currently an increasing demand to have detailed hazard maps available to be able to consider other risk-reducing measures as well. Hazard maps are a prerequisite for spatial planning, but can also support emergency management, the design of flood mitigation measures, and the setting of insurance policies. The increase in flood risks due to population growth and economic development in hazardous areas in the past shows that sensible spatial planning is crucial to prevent risks increasing further. Assigning the least hazardous locations for development or adapting developments to the actual hazard requires comprehensive flood hazard maps. Since flood hazard is a multi-dimensional phenomenon, many different maps could be relevant. Having large numbers of maps to take into account does not, however, make planning easier. To support flood risk management planning we therefore introduce a new approach in which all relevant flood hazard parameters can be combined into two comprehensive maps of flood damage hazard and flood fatality hazard.

  9. Flood fatality hazard and flood damage hazard: combining multiple hazard characteristics into meaningful maps for spatial planning

    NASA Astrophysics Data System (ADS)

    de Bruijn, K. M.; Klijn, F.; van de Pas, B.; Slager, C. T. J.

    2015-01-01

    For comprehensive flood risk management, accurate information on flood hazards is crucial. While in the past an estimate of potential flood consequences in large areas was often sufficient to make decisions on flood protection, there currently is an increasing demand to have detailed hazard maps available to be able to consider other risk reducing measures as well. Hazard maps are a prerequisite for spatial planning, but can also support emergency management, the design of flood mitigation measures, and the setting of insurance policies. The increase in flood risks due to population growth and economic development in hazardous areas in the past shows that sensible spatial planning is crucial to prevent risks increasing further. Assigning the least hazardous locations for development or adapting developments to the actual hazard requires comprehensive flood hazard maps. Since flood hazard is a multi-dimensional phenomenon, many different maps could be relevant. Having large numbers of maps to take into account does, however, not make planning easier. To support flood risk management planning we therefore introduce a new approach in which all relevant flood hazard parameters can be combined into two comprehensive maps of flood damage hazard respectively flood fatality hazard.

  10. Predicting siRNA efficacy based on multiple selective siRNA representations and their combination at score level

    PubMed Central

    He, Fei; Han, Ye; Gong, Jianting; Song, Jiazhi; Wang, Han; Li, Yanwen

    2017-01-01

    Small interfering RNAs (siRNAs) may induce to targeted gene knockdown, and the gene silencing effectiveness relies on the efficacy of the siRNA. Therefore, the task of this paper is to construct an effective siRNA prediction method. In our work, we try to describe siRNA from both quantitative and qualitative aspects. For quantitative analyses, we form four groups of effective features, including nucleotide frequencies, thermodynamic stability profile, thermodynamic of siRNA-mRNA interaction, and mRNA related features, as a new mixed representation, in which thermodynamic of siRNA-mRNA interaction is introduced to siRNA efficacy prediction for the first time to our best knowledge. And then an F-score based feature selection is employed to investigate the contribution of each feature and remove the weak relevant features. Meanwhile, we encode the siRNA sequence and existed empirical design rules as a qualitative siRNA representation. These two kinds of siRNA representations are combined to predict siRNA efficacy by supported Vector Regression (SVR) at score level. The experimental results indicate that our method may select the features with powerful discriminative ability and make the two kinds of siRNA representations work at full capacity. The prediction results also demonstrate that our method can outperform other popular siRNA efficacy prediction algorithms. PMID:28317874

  11. Combining Multiple Hypothesis Testing with Machine Learning Increases the Statistical Power of Genome-wide Association Studies

    NASA Astrophysics Data System (ADS)

    Mieth, Bettina; Kloft, Marius; Rodríguez, Juan Antonio; Sonnenburg, Sören; Vobruba, Robin; Morcillo-Suárez, Carlos; Farré, Xavier; Marigorta, Urko M.; Fehr, Ernst; Dickhaus, Thorsten; Blanchard, Gilles; Schunk, Daniel; Navarro, Arcadi; Müller, Klaus-Robert

    2016-11-01

    The standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008–2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0.

  12. 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.

  13. 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

  14. Automatic hippocampus segmentation of 7.0 Tesla MR images by combining multiple atlases and auto-context models

    PubMed Central

    Kim, Minjeong; Wu, Guorong; Li, Wei; Wang, Li; Son, Young-Don; Cho, Zang-Hee; Shen, Dinggang

    2014-01-01

    In many neuroscience and clinical studies, accurate measurement of hippocampus is very important to reveal the inter-subject anatomical differences or the subtle intra-subject longitudinal changes due to aging or dementia. Although many automatic segmentation methods have been developed, their performances are still challenged by the poor image contrast of hippocampus in the MR images acquired especially from 1.5 or 3.0 Tesla (T) scanners. With the recent advance of imaging technology, 7.0 T scanner provides much higher image contrast and resolution for hippocampus study. However, the previous methods developed for segmentation of hippocampus from 1.5 T or 3.0 T images do not work for the 7.0 T images, due to different levels of imaging contrast and texture information. In this paper, we present a learning-based algorithm for automatic segmentation of hippocampi from 7.0 T images, by taking advantages of the state-of-the-art multi-atlas framework and also the auto-context model (ACM). Specifically, ACM is performed in each atlas domain to iteratively construct sequences of location-adaptive classifiers by integrating both image appearance and local context features. Due to the plenty texture information in 7.0 T images, more advanced texture features are also extracted and incorporated into the ACM during the training stage. Then, under the multi-atlas segmentation framework, multiple sequences of ACM-based classifiers are trained for all atlases to incorporate the anatomical variability. In the application stage, for a new image, its hippocampus segmentation can be achieved by fusing the labeling results from all atlases, each of which is obtained by applying the atlas-specific ACM-based classifiers. Experimental results on twenty 7.0 T images with the voxel size of 0.35 × 0.35 × 0.35 mm3 show very promising hippocampus segmentations (in terms of Dice overlap ratio 89.1 ± 0.020), indicating high applicability for the future clinical and neuroscience studies

  15. Combined gene expression and proteomic analysis of EGF induced apoptosis in A431 cells suggests multiple pathways trigger apoptosis.

    PubMed

    Alanazi, Ibrahim; Ebrahimie, Esmaeil; Hoffmann, Peter; Adelson, David L

    2013-11-01

    A431 cells, derived from epidermoid carcinoma, overexpress the epidermal growth factor receptor (EGFR) and when treated with a high dose of EGF will undergo apoptosis. We exploited microarray and proteomics techniques and network prediction to study the regulatory mechanisms of EGF-induced apoptosis in A431 cells. We observed significant changes in gene expression in 162 genes, approximately evenly split between pro-apoptotic and anti-apoptotic genes and identified 30 proteins from the proteomic data that had either pro or anti-apoptotic annotation. Our correlation analysis of gene expression and proteome modeled a number of distinct sub-networks that are associated with the onset of apoptosis, allowing us to identify specific pathways and components. These include components of the interferon signalling pathway, and down stream components, including cytokines and suppressors of cytokine signalling. A central component of almost all gene expression sub-networks identified was TP53, which is mutated in A431 cells, and was down regulated. This down regulation of TP53 appeared to be correlated with proteomic sub-networks of cytoskeletal or cell adhesion components that might induce apoptosis by triggering cytochrome C release. Of the only three genes also differentially expressed as proteins, only serpinb1 had a known association with apoptosis. We confirmed that up regulation and cleavage of serpinb1 into L-DNAaseII was correlated with the induction of apoptosis. It is unlikely that a single pathway, but more likely a combination of pathways is needed to trigger EGF induced apoptosis in A431cells.

  16. Thiocyanate complexes of uranium in multiple oxidation states: a combined structural, magnetic, spectroscopic, spectroelectrochemical, and theoretical study.

    PubMed

    Hashem, Emtithal; Platts, James A; Hartl, František; Lorusso, Giulia; Evangelisti, Marco; Schulzke, Carola; Baker, Robert J

    2014-08-18

    A comprehensive study of the complexes A4[U(NCS)8] (A = Cs, Et4N, (n)Bu4N) and A3[UO2(NCS)5] (A = Cs, Et4N) is described, with the crystal structures of [(n)Bu4N]4[U(NCS)8]·2MeCN and Cs3[UO2(NCS)5]·O0.5 reported. The magnetic properties of square antiprismatic Cs4[U(NCS)8] and cubic [Et4N]4[U(NCS)8] have been probed by SQUID magnetometry. The geometry has an important impact on the low-temperature magnetic moments: at 2 K, μeff = 1.21 μB and 0.53 μB, respectively. Electronic absorption and photoluminescence spectra of the uranium(IV) compounds have been measured. The redox chemistry of [Et4N]4[U(NCS)8] has been explored using IR and UV-vis spectroelectrochemical methods. Reversible 1-electron oxidation of one of the coordinated thiocyanate ligands occurs at +0.22 V vs Fc/Fc(+), followed by an irreversible oxidation to form dithiocyanogen (NCS)2 which upon back reduction regenerates thiocyanate anions coordinating to UO2(2+). NBO calculations agree with the experimental spectra, suggesting that the initial electron loss of [U(NCS)8](4-) is delocalized over all NCS(-) ligands. Reduction of the uranyl(VI) complex [Et4N]3[UO2(NCS)5] to uranyl(V) is accompanied by immediate disproportionation and has only been studied by DFT methods. The bonding in [An(NCS)8](4-) (An = Th, U) and [UO2(NCS)5](3-) has been explored by a combination of DFT and QTAIM analysis, and the U-N bonds are predominantly ionic, with the uranyl(V) species more ionic that the uranyl(VI) ion. Additionally, the U(IV)-NCS ion is more ionic than what was found for U(IV)-Cl complexes.

  17. 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

  18. Effect of Combination Exercise Therapy on Walking Distance, Postural Balance, Fatigue and Quality of Life in Multiple Sclerosis Patients: A Clinical Trial Study

    PubMed Central

    Sangelaji, Bahram; Nabavi, Seyed Massood; Estebsari, Fatemeh; Banshi, Mohammad Reza; Rashidian, Hamideh; Jamshidi, Ensiyeh; Dastoorpour, Maryam

    2014-01-01

    Background: Multiple Sclerosis (MS) is a demyelinating disease of the nervous system which has numerous disabling effects on patients. Objectives: This study aimed at investigating the short- and long-term effects of a period of combination exercise therapy on walking distance, balance, fatigue and quality of life in multiple sclerosis patients referred to the physiotherapy clinic of Iran's Multiple Sclerosis Society in 2013. Patients and Methods: This study was a randomized controlled clinical trial on 59 patients divided into the intervention (n = 39) and control groups (n = 20). The intervention group received 10 weeks of combination therapy including aerobic, strengthening, balancing and stretching exercises. A week before, a week later and a year after the beginning of the exercises, both groups of patients received BBSS, six minute walking, Family Support Services (FSS), Expanded Disability Status Scale (EDSS) and quality of life tests. The scores of two groups were then compared using statistical tests such as repeated measures ANOVA test. Results: The results indicated significant changes in the intervention group in comparison to the control group in the second phase of the study comparing to the first one for all tests except EDSS (Mean difference scores of EDSS: -0.13), P-value = 0.60; FSS: -6.9, P-value = 0.02, Mental Quality of Life (QOL): 16.36, P-value = 0.001; Physical QOL: 12.17, P-value = 0.001, six minute walking: 137.2, P-value < 0.0001; and Berg: 3.34, P-value < 0.0001. These changes were not significant in the second phase of the study comparing to the third one; however, they were again significant in the third phase comparing to the first phase of the study (P < 0.05). Conclusions: Exercise has significant effect on improving symptoms of multiple sclerosis, and cessation of exercise may cause recurrence of symptoms in the intervention group with a slope similar to that of the control group. Therefore, continuous rather than short period

  19. Intraluminal Blockade of Cell-Surface CD74 and Glucose Regulated Protein 78 Prevents Substance P-Induced Bladder Inflammatory Changes in the Rat

    PubMed Central

    Vera, Pedro L.; Wang, Xihai; Bucala, Richard J.; Meyer-Siegler, Katherine L.

    2009-01-01

    Background Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine constitutively expressed by urothelial cells. During inflammatory stimuli, MIF is released into the lumen complexed to other proteins and these complexes can bind to urothelial cell-surface receptors to activate signaling pathways. Since MIF is complexed to α1-inhibitor III (A1-I3; a member of the α2-macroglubulin family) and glucose regulated protein 78 (GRP78) is a receptor for A1-I3 the goals of this study were to determine if substance P elicits urothelial cell-surface expression of GRP78 and to assess the functional role of CD74 (receptor for MIF) or GRP78 in substance P-induced bladder inflammatory changes. Methodology/Principal Findings Anesthetized male Sprague-Dawley rats received either saline or substance P (s.c.), bladders were collected 1 hour after treatment and processed for histology or protein/mRNA. The expression of GRP78 at urothelial cell-surface was determined by performing in vivo biotinylation of urothelial cell-surface proteins. Finally, in order to determine the effects of receptor blockade on substance P-induced MIF release and inflammatory changes, rats received either intraluminal antibodies to CD74, GRP78, both, or non-specific IgG (as a control). GRP78 and MIF immunostaining was simultaneously visualized in umbrella cells only after substance P treatment. Immunoprecipitation studies showed GRP78-MIF complexes increased after substance P while in vivo biotinylation confirmed substance P-induced GRP78 cell-surface expression in urothelial cells. Intraluminal blockade of CD74 and/or GRP78 prevented substance P-induced changes, including bladder edema, intraluminal MIF release by urothelial cells and production of inflammatory cytokines by urothelial cells. Conclusions/Significance GRP78 is expressed on the surface of urothelial cells after substance P treatment where it can bind MIF complexes. Blocking CD74 (receptor for MIF) and/or GRP78 prevented

  20. 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

  1. 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

  2. Phase 1/2 study of lenalidomide combined with low-dose cyclophosphamide and prednisone in lenalidomide-refractory multiple myeloma.

    PubMed

    Nijhof, Inger S; Franssen, Laurens E; Levin, Mark-David; Bos, Gerard M J; Broijl, Annemiek; Klein, Saskia K; Koene, Harry R; Bloem, Andries C; Beeker, Aart; Faber, Laura M; van der Spek, Ellen; Ypma, Paula F; Raymakers, Reinier; van Spronsen, Dick-Johan; Westerweel, Peter E; Oostvogels, Rimke; van Velzen, Jeroen; van Kessel, Berris; Mutis, Tuna; Sonneveld, Pieter; Zweegman, Sonja; Lokhorst, Henk M; van de Donk, Niels W C J

    2016-09-19

    The prognosis of multiple myeloma (MM) patients who become refractory to lenalidomide and bortezomib is very poor, indicating the need for new therapeutic strategies for these patients. Next to the development of new drugs, the strategy of combining agents with synergistic activity may also result in clinical benefit for patients with advanced myeloma. We have previously shown in a retrospective analysis that lenalidomide combined with continuous low-dose cyclophosphamide and prednisone (REP) had remarkable activity in heavily pretreated, lenalidomide-refractory MM patients. To evaluate this combination prospectively, we initiated a phase 1/2 study to determine the optimal dose and to assess its efficacy and safety in lenalidomide-refractory MM patients. The maximum tolerated dose (MTD) was defined as 25 mg lenalidomide (days 1-21/28 days), combined with continuous cyclophosphamide (50 mg/day) and prednisone (20 mg/day). At the MTD (n=67 patients), the overall response rate was 67%, and at least minimal response was achieved in 83% of the patients. Median PFS and OS were 12.1 and 29.0 months, respectively. Similar results were achieved in the subset of patients with lenalidomide- and bortezomib-refractory disease as well as in patients with high-risk cytogenetic abnormalities, defined as t(4;14), t(14;16), del(17p), and/or ampl(1q) as assessed by FISH. Neutropenia (22%) and thrombocytopenia (22%) were the most common grade 3-4 hematologic adverse events. Infections (21%) were the most common grade 3-5 non-hematologic adverse events. In conclusion, the addition of continuous low-dose oral cyclophosphamide to lenalidomide and prednisone offers a new therapeutic perspective for multidrug refractory MM patients. This trial was registered at www.clinicaltrials.gov as #NCT01352338.

  3. 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).

  4. 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.; ...

    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

  5. 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.

  6. 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 Tc cuprates

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

    Some of the most exotic material properties derive from electronic states with short correlation length (~10-500 {\\AA}), suggesting that the local structural symmetry may play a relevant role in their behavior. Here 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 La$_{1.875}$Ba$_{0.125}$CuO$_4$, in which the response of electronic order to pressure can only be understood by probing the structure at the relevant length scales.

  7. 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

  8. Six-band terahertz metamaterial absorber based on the combination of multiple-order responses of metallic patches in a dual-layer stacked resonance structure

    PubMed Central

    Wang, Ben-Xin; Wang, Gui-Zhen; Sang, Tian; Wang, Ling-Ling

    2017-01-01

    This paper reports on a numerical study of the six-band metamaterial absorber composed of two alternating stack of metallic-dielectric layers on top of a continuous metallic plane. Six obvious resonance peaks with high absorption performance (average larger than 99.37%) are realized. The first, third, fifth, and the second, fourth, sixth resonance absorption bands are attributed to the multiple-order responses (i.e., the 1-, 3- and 5-order responses) of the bottom- and top-layer of the structure, respectively, and thus the absorption mechanism of six-band absorber is due to the combination of two sets of the multiple-order resonances of these two layers. Besides, the size changes of the metallic layers have the ability to tune the frequencies of the six-band absorber. Employing the results, we also present a six-band polarization tunable absorber through varying the sizes of the structure in two orthogonal polarization directions. Moreover, nine-band terahertz absorber can be achieved by using a three-layer stacked structure. Simulation results indicate that the absorber possesses nine distinct resonance bands, and average absorptivities of them are larger than 94.03%. The six-band or nine-band absorbers obtained here have potential applications in many optoelectronic and engineering technology areas. PMID:28120897

  9. The Complex Surgical Management of the First Case of Severe Combined Immunodeficiency and Multiple Intestinal Atresias Surviving after the Fourth Year of Life

    PubMed Central

    Garofano, Salvatore; Teruzzi, Elisabetta; Vinardi, Simona; Carbonaro, Giulia; Cerrina, Alessia; Morra, Isabella; Montin, Davide; Mussa, Alessandro; Schleef, Jürgen

    2014-01-01

    Severe combined immunodeficiency (SCID) is a life-threatening syndrome of recurrent infections and gastrointestinal alterations due to severe compromise of T cells and B cells. Clinically, most patients present symptoms before the age of 3 months and without intervention SCID usually results in severe infections and death by the age of 2 years. Its association with intestinal anomalies as multiple intestinal atresias (MIA) is rare and worsens the prognosis, resulting lethal. We describe the case of a four year-old boy with SCID-MIA. He presented at birth with meconium peritonitis, multiple ileal atresias and underwent several intestinal resections. A targeted Sanger sequencing revealed a homozygous 4-bp deletion (c.313ΔTATC; p.Y105fs) in tetratricopeptide repeat domain 7A (TTC7A). He experienced surgical procedures including resection and stricturoplasty. Despite parenteral nutrition-associated liver disease, the patient is surviving at the time of writing the report. Precocious immune system assessment, scrutiny of TTC7A mutations and prompt surgical procedures are crucial in the management. PMID:25587526

  10. Bortezomib combined with lenalidomide as the first-line treatment for the rare synchronous occurrence of multiple myeloma and pulmonary adenocarcinoma

    PubMed Central

    Zuo, Wenli; Zhu, Xinghu; Yang, Jingke; Mei, Zhenyang; Deng, Mei; Lin, Quande; Song, Yongping; Yin, Qingsong

    2017-01-01

    Abstract Background: Simultaneous multiple myeloma (MM) and pulmonary adenocarcinoma is a rare occurrence, and thus, treatment is a challenge. This study reports on 1 such case of MM with concurrent lung cancer, where an accurate diagnosis was made and the patient underwent treatment for both cancers. Case summary: A 68-year-old man presented with 2 months of progressive lower back pain. Visualization with magnetic resonance imaging (MRI) revealed multiple collapsed vertebrae from T12 to S3, as well as an altered signal intensity at the T3 vertebra. The patient was diagnosed with MM upon examination. A chest computed tomography (CT) scan revealed a round mass in the left lower lobe of the lungs, and a CT-guided needle biopsy uncovered a moderately differentiated adenocarcinoma. There were no additional notable findings in the left lung using positron emission tomography computed tomography (PET-CT). Therefore, a diagnosis of MM with pulmonary adenocarcinoma was made. Surgery was performed to excise the lung cancer. Bortezomib was used as first-line induction therapy against both tumors and lenalidomide was used for maintenance. The patient went into complete remission. Using this combined chemotherapy, the patient has survived for over 3 years since a diagnosis was made despite relapsing twice after the first year. Conclusion: This report clearly delineates the diagnosis and treatment of a rare case of synchronous MM and pulmonary adenocarcinoma, as well as depicts a potentially positive outcome for the patient. It also overviews some diagnostic and therapeutic implications for clinicians. PMID:28072730

  11. ACM-based automatic liver segmentation from 3-D CT images by combining multiple atlases and improved mean-shift techniques.

    PubMed

    Ji, Hongwei; He, Jiangping; Yang, Xin; Deklerck, Rudi; Cornelis, Jan

    2013-05-01

    In this paper, we present an autocontext model(ACM)-based automatic liver segmentation algorithm, which combines ACM, multiatlases, and mean-shift techniques to segment liver from 3-D CT images. Our algorithm is a learning-based method and can be divided into two stages. At the first stage, i.e., the training stage, ACM is performed to learn a sequence of classifiers in each atlas space (based on each atlas and other aligned atlases). With the use of multiple atlases, multiple sequences of ACM-based classifiers are obtained. At the second stage, i.e., the segmentation stage, the test image will be segmented in each atlas space by applying each sequence of ACM-based classifiers. The final segmentation result will be obtained by fusing segmentation results from all atlas spaces via a multiclassifier fusion technique. Specially, in order to speed up segmentation, given a test image, we first use an improved mean-shift algorithm to perform over-segmentation and then implement the region-based image labeling instead of the original inefficient pixel-based image labeling. The proposed method is evaluated on the datasets of MICCAI 2007 liver segmentation challenge. The experimental results show that the average volume overlap error and the average surface distance achieved by our method are 8.3% and 1.5 m, respectively, which are comparable to the results reported in the existing state-of-the-art work on liver segmentation.

  12. Six-band terahertz metamaterial absorber based on the combination of multiple-order responses of metallic patches in a dual-layer stacked resonance structure

    NASA Astrophysics Data System (ADS)

    Wang, Ben-Xin; Wang, Gui-Zhen; Sang, Tian; Wang, Ling-Ling

    2017-01-01

    This paper reports on a numerical study of the six-band metamaterial absorber composed of two alternating stack of metallic-dielectric layers on top of a continuous metallic plane. Six obvious resonance peaks with high absorption performance (average larger than 99.37%) are realized. The first, third, fifth, and the second, fourth, sixth resonance absorption bands are attributed to the multiple-order responses (i.e., the 1-, 3- and 5-order responses) of the bottom- and top-layer of the structure, respectively, and thus the absorption mechanism of six-band absorber is due to the combination of two sets of the multiple-order resonances of these two layers. Besides, the size changes of the metallic layers have the ability to tune the frequencies of the six-band absorber. Employing the results, we also present a six-band polarization tunable absorber through varying the sizes of the structure in two orthogonal polarization directions. Moreover, nine-band terahertz absorber can be achieved by using a three-layer stacked structure. Simulation results indicate that the absorber possesses nine distinct resonance bands, and average absorptivities of them are larger than 94.03%. The six-band or nine-band absorbers obtained here have potential applications in many optoelectronic and engineering technology areas.

  13. Intraluminal pressure, transmucosal potential difference, and pH studies in the oesophagus of patients before and after Collis repair of a hiatal hernia

    PubMed Central

    Habibulla, K. S.; Collis, J. Leigh

    1973-01-01

    Intraluminal pressure, transmucosal potential difference, and endo-oesophageal pH measurements were studied in patients with hiatal hernia—before and after a hiatal repair. The operation employed is the Collis (1968) repair for uncomplicated hiatal hernia and does not refer to gastroplasty as recommended for peptic stricture (Collis, 1961). Postoperative studies show that the repair approximates the inferior oesophageal sphincter to the hiatus with the production of a single band of raised pressure at the lower end of the oesophagus. This band is similar to that seen in normal subjects and its appearance was associated with cure of the symptoms, abolition of the gastro-oesophageal reflux, and improvement in the function of the inferior oesophageal sphincter and the musculature of the body of the oesophagus. Certain physiological implications of this study are discussed. Images PMID:4724501

  14. Pomalidomide in combination with dexamethasone results in synergistic anti-tumour responses in pre-clinical models of lenalidomide-resistant multiple myeloma.

    PubMed

    Rychak, Emily; Mendy, Derek; Shi, Tao; Ning, Yuhong; Leisten, Jim; Lu, Ling; Miller, Karen; Narla, Rama K; Orlowski, Robert Z; Raymon, Heather K; Bjorklund, Chad C; Thakurta, Anjan; Gandhi, Anita K; Cathers, Brian E; Chopra, Rajesh; Daniel, Thomas O; Lopez-Girona, Antonia

    2016-03-01

    Pomalidomide is an IMiD(®) immunomodulatory agent, which has shown clinically significant benefits in relapsed and/or refractory multiple myeloma (rrMM) patients when combined with dexamethasone, regardless of refractory status to lenalidomide or bortezomib. (Schey et al, ; San Miguel et al, 2013; Richardson et al, 2014; Scott, ) In this work, we present preclinical data showing that the combination of pomalidomide with dexamethasone (PomDex) demonstrates potent anti-proliferative and pro-apoptotic activity in both lenalidomide-sensitive and lenalidomide-resistant MM cell lines. PomDex also synergistically inhibited tumour growth compared with single-agent treatment in xenografts of lenalidomide-resistant H929 R10-1 cells. Typical hallmarks of IMiD compound activity, including IKZF3 (Aiolos) degradation, and the downregulation of interferon regulatory factor (IRF) 4 and MYC, seen in lenalidomide-sensitive H929 MM cell lines, were also observed in PomDex-treated lenalidomide-resistant H929 MM cells. Remarkably, this resulted in strong, synergistic effects on the induction of apoptosis in both lenalidomide-sensitive and resistant MM cells. Furthermore, gene expression profiling revealed a unique differential gene expression pattern in PomDex-treated samples, highlighted by the modulation of pro-apoptotic pathways in lenalidomide-resistant cells. These results provide key insights into molecular mechanisms of PomDex in the lenalidomide-resistant setting.

  15. 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

  16. 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.

  17. 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.

  18. Direct analysis in real time mass spectrometry combined with single-drop liquid-liquid-liquid microextraction for the rapid analysis of multiple phytohormones in fruit juice.

    PubMed

    Bai, Yu; Zhang, Jialing; Bai, Yu; Liu, Huwei

    2012-06-01

    A rapid, simple, and efficient method for the fast determination of multiple phytohormones was developed in this work, based on single-drop liquid-liquid-liquid microextraction (SD-LLLME) combined with direct analysis in real-time mass spectrometry (DART-MS). Six phytohormones--indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and gibberellin A(3) (GA(3))--were analyzed simultaneously using this method, and the conditions employed for DART-MS and SD-LLLME were optimized systematically. Satisfactory results were obtained in terms of linearity (R (2) values for all phytohormones were 0.991-0.996), sensitivity (limits of detection were 0.65-72 ng/mL), and repeatability (RSD values were 6.9-14%). In addition, the proposed method was applied to determine the endogenous phytohormones in three kinds of fruit juice. Different concentrations of phytohormones were detected with satisfactory recoveries, and the whole analytical procedure took no more than 30 min. Therefore, this combination of SD-LLLME and DART-MS was shown to be a suitable and effective approach for the fast analysis of targets present at trace level concentrations in complex matrices.

  19. Regulation of Epithelial Differentiation in Rat Intestine by Intraluminal Delivery of an Adenoviral Vector or Silencing RNA Coding for Schlafen 3

    PubMed Central

    Kovalenko, Pavlo L.; Yuan, Lisi; Sun, Kelian; Kunovska, Lyudmyla; Seregin, Sergey; Amalfitano, Andrea; Basson, Marc D.

    2013-01-01

    Although we stimulate enterocytic proliferation to ameliorate short gut syndrome or mucosal atrophy, less effort has been directed at enterocytic differentiation. Schlafen 3 (Slfn3) is a poorly understood protein induced during IEC-6 enterocytic differentiation. We hypothesized that exogenous manipulation of Slfn3 would regulate enterocytic differentiation in vivo. Adenoviral vector coding for Slfn3 cDNA (Ad-GFP-Slfn3) or silencing RNA for Slfn3 (siSlfn3) was introduced intraluminally into rat intestine. We assessed Slfn3, villin, sucrase-isomaltase (SI), Dpp4, and Glut2 by qRT-PCR, Western blot, and immunohistochemistry. We also studied Slfn3 and these differentiation markers in atrophic defunctionalized jejunal mucosa and the crypt-villus axis of normal jejunum. Ad-GFP-Slfn3 but not Ad-GFP increased Slfn3, villin and Dpp4 expression in human Caco-2 intestinal epithelial cells. Injecting Ad-GFP-Slfn3 into rat jejunum in vivo increased mucosal Slfn3 mRNA three days later vs. intraluminal Ad-GFP. This Slfn3 overexpression was associated with increases in all four differentiation markers. Injecting siSlfn3 into rat jejunum in vivo substantially reduced Slfn3 and all four intestinal mucosal differentiation markers three days later, as well as Dpp4 specific activity. Endogenous Slfn3 was reduced in atrophic mucosa from a blind-end Roux-en-Y anastomosis in parallel with differentiation marker expression together with AKT and p38 signaling. Slfn3 was more highly expressed in the villi than the crypts, paralleling Glut2, SI and Dpp4. Slfn3 is a key intracellular regulator of rat enterocytic differentiation. Understanding how Slfn3 works may identify targets to promote enterocytic differentiation and maintain mucosal function in vivo, facilitating enteral nutrition and improving survival in patients with mucosal atrophy or short gut syndrome. PMID:24244554

  20. A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens.

    PubMed

    Sanchez, Larysa; Vesole, David H; Richter, Joshua R; Biran, Noa; Bilotti, Elizabeth; McBride, Laura; Anand, Palka; Ivanovski, Kristin; Siegel, David S

    2017-02-01

    Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open-label, single-institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide-refractory patients. Patients were considered lenalidomide-refractory if they had no clinical response (combination with lenalidomide and dexamethasone was active in lenalidomide-refractory patients.

  1. 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

  2. A phase 2 safety study of accelerated elotuzumab infusion, over less than 1 hour, in combination with lenalidomide and dexamethasone, in patients with multiple myeloma.

    PubMed

    Berenson, James; Manges, Robert; Badarinath, Suprith; Cartmell, Alan; McIntyre, Kristi; Lyons, Roger; Harb, Wael; Mohamed, Hesham; Nourbakhsh, Ali; Rifkin, Robert

    2017-02-18

    Elotuzumab, an immunostimulatory SLAMF7-targeting monoclonal antibody, induces myeloma cell death with minimal effects on normal tissue. In a previous phase 3 study in patients with relapsed/refractory multiple myeloma (RRMM), elotuzumab (10 mg/kg, ∼3-hour infusion), combined with lenalidomide and dexamethasone, demonstrated durable efficacy and acceptable safety; 10% (33/321) of patients had infusion reactions (IRs; Grade 1/2: 29; Grade 3: 4). This phase 2 study (NCT02159365) investigated an accelerated infusion schedule in 70 patients with newly diagnosed multiple myeloma or RRMM. The primary endpoint was cumulative incidence of Grade 3/4 IRs by completion of treatment Cycle 2. Dosing comprised elotuzumab 10 mg/kg intravenously (weekly, Cycles 1-2; biweekly, Cycles 3+), lenalidomide 25 mg (daily, Days 1-21) and dexamethasone (28 mg orally and 8 mg intravenously, weekly, Cycles 1-2; 40 mg orally, weekly, Cycles 3+), in 28-day cycles. Premedication with diphenhydramine, acetaminophen, and ranitidine (or their equivalents) was given as in previous studies. If no IRs occurred, infusion rate was increased in Cycle 1 from 0.5 to 2 mL/min during dose 1 (∼2 hours 50 min duration) to 5 mL/min for the entire infusion by dose 3 and also during all subsequent infusions (∼1-hour duration). Median number of treatment cycles was six. No Grade 3/4 IRs occurred; only one Grade 1 and one Grade 2 IR occurred, both during the first infusion. These data support the safety of a faster infusion of elotuzumab administered over ∼1 hour by the third dose, providing a more convenient alternative dosing option for patients. This article is protected by copyright. All rights reserved.

  3. 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

  4. 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

  5. Inhibitory effect of epirubicin-loaded lipid microbubbles with conjugated anti-ABCG2 antibody combined with therapeutic ultrasound on multiple myeloma cancer stem cells.

    PubMed

    Shi, Fangfang; Yang, Fang; He, Xiangfeng; Zhang, Ying; Wu, Songyan; Li, Miao; Zhang, Yunxia; Di, Wu; Dou, Jun; Gu, Ning

    2016-01-01

    Ultrasound-targeted microbubble destruction (UTMD) technique is thought to improve the chemotherapeutic agent delivery from microbubbles (MBs) in tumor tissues and reduce the side effects in non-tumor tissues. Multiple myeloma (MM) is a bone marrow cancer and remains to be an incurable disease. In this study, we used the UTMD technique to investigate the inhibitory effect of our developed novel reagent on MM cancer stem cells (CD138(-)CD34(-)MM CSCs) that are MM cells with CD138(-)CD34(-) phenotypes, responsible for MM-initiating potential, drug resistance and eventual relapse. The preparatory steps of novel reagent was first epirubicin (EPI)-loaded in the lipid MBs that was consisted of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]-biotin, dipalmitoyl-phosphatidylglycerol and 25-NBD-cholesterol, then anti-ABCG2 monoclonal antibody (mAb) was conjugated onto the MB surface to form EPI-MBs+mAb. CD138(-)CD34(-)MM CSCs were isolated from human MM RPMI 8226 cell line by the magnetic associated cell sorting method. The results showed that the attenuated proliferation, migration and invasion ability, and increased apoptosis were observed when MM CSCs were incubated with a various agents. EPI-MBs+mAb combined with therapeutic ultrasound significantly promoted the MM CSC apoptosis compared with EPI, EPI-MBs alone or EPI-MBs+mAb without ultrasound exposure. These results suggest that the developed EPI-MBs+mAb combined with therapeutic ultrasound remarkably induced MM CSC apoptosis in vitro.

  6. 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.

  7. 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.

  8. XPO1 inhibitor combination therapy with bortezomib or carfilzomib induces nuclear localization of IκBα and overcomes acquired proteasome inhibitor resistance in human multiple myeloma.

    PubMed

    Turner, Joel G; Kashyap, Trinayan; Dawson, Jana L; Gomez, Juan; Bauer, Alexis A; Grant, Steven; Dai, Yun; Shain, Kenneth H; Meads, Mark; Landesman, Yosef; Sullivan, Daniel M

    2016-11-29

    Acquired proteasome-inhibitor (PI) resistance is a major obstacle in the treatment of multiple myeloma (MM). We investigated whether the clinical XPO1-inhibitor selinexor, when combined with bortezomib or carfilzomib, could overcome acquired resistance in MM. PI-resistant myeloma cell lines both in vitro and in vivo and refractory myeloma patient biopsies were treated with selinexor/bortezomib or carfilzomib and assayed for apoptosis. Mechanistic studies included NFκB pathway protein expression assays, immunofluorescence microscopy, ImageStream flow-cytometry, and proximity-ligation assays. IκBα knockdown and NFκB activity were measured in selinexor/bortezomib-treated MM cells. We found that selinexor restored sensitivity of PI-resistant MM to bortezomib and carfilzomib. Selinexor/bortezomib treatment inhibited PI-resistant MM tumor growth and increased survival in mice. Myeloma cells from PI-refractory MM patients were sensitized by selinexor to bortezomib and carfilzomib without affecting non-myeloma cells. Immunofluorescence microscopy, Western blot, and ImageStream analyses of MM cells showed increases in total and nuclear IκBα by selinexor/bortezomib. Proximity ligation found increased IκBα-NFκB complexes in treated MM cells. IκBα knockdown abrogated selinexor/bortezomib-induced cytotoxicity in MM cells. Selinexor/bortezomib treatment decreased NFκB transcriptional activity. Selinexor, when used with bortezomib or carfilzomib, has the potential to overcome PI drug resistance in MM. Sensitization may be due to inactivation of the NFκB pathway by IκBα.

  9. Observation of multiple vibrational modes in ultrahigh vacuum tip-enhanced Raman spectroscopy combined with molecular-resolution scanning tunneling microscopy.

    PubMed

    Jiang, N; Foley, E T; Klingsporn, J M; Sonntag, M D; Valley, N A; Dieringer, J A; Seideman, T; Schatz, G C; Hersam, M C; Van Duyne, R P

    2012-10-10

    Multiple vibrational modes have been observed for copper phthalocyanine (CuPc) adlayers on Ag(111) using ultrahigh vacuum (UHV) tip-enhanced Raman spectroscopy (TERS). Several important new experimental features are introduced in this work that significantly advance the state-of-the-art in UHV-TERS. These include (1) concurrent sub-nm molecular resolution STM imaging using Ag tips with laser illumination of the tip-sample junction, (2) laser focusing and Raman collection optics that are external to the UHV-STM that has two cryoshrouds for future low temperature experiments, and (3) all sample preparation steps are carried out in UHV to minimize contamination and maximize spatial resolution. Using this apparatus we have been able to demonstrate a TERS enhancement factor of 7.1 × 10(5). Further, density-functional theory calculations have been carried out that allow quantitative identification of eight different vibrational modes in the TER spectra. The combination of molecular-resolution UHV-STM imaging with the detailed chemical information content of UHV-TERS allows the interactions between large polyatomic molecular adsorbates and specific binding sites on solid surfaces to be probed with unprecedented spatial and spectroscopic resolution.

  10. Effect of Multiple-Jets Exits on the Base Pressure of a Simple Wing-Body Combination at Mach Numbers of 0.6 to 1.27

    NASA Technical Reports Server (NTRS)

    Cubbage, James M., Jr.

    1959-01-01

    An investigation has been conducted at Mach numbers of 0.6 to 1.27 to determine the effect of multiple-jet exits on the base pressure of a simple wing-body combination. The design Mach number of the nozzles ranged from 1 to 3 at jet exit diameters equal to 36.4 to 75 percent of the model thickness. Jet total-pressure to free-stream static-pressure ratios ranged from 1 (no flow) to 34.2. The results show that the variation of base pressure coefficient with jet pressure ratio for the model tested was similar to that obtained for single nozzles in bodies of revolution in other investigations. As in the case for single jets the base pressure coefficient for the present model became less negative as the jet exit diameter increased. For a constant throat diameter and an assumed schedule of jet pressure ratio over the speed range of these tests, nozzle Mach number had only a small effect on base pressure coefficient.

  11. 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.

  12. 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.

  13. Reduction of multiplicity of infections but no change in msp2 genetic diversity in Plasmodium falciparum isolates from Congolese children after introduction of artemisinin-combination therapy

    PubMed Central

    2012-01-01

    Background In this first study conducted after the introduction of artemisinin-combination therapy (ACT), the major objective was to evaluate Plasmodium falciparum genetic diversity and multiplicity of infection in isolates from Congolese children between one and nine years of age enrolled and followed up for one year. The secondary objective was to characterize the msp2 profiles of P. falciparum isolates collected from successive malaria episodes in ten children who had four or more clinical episodes during the follow up. Methods Three-hundred and thirteen children residing in southern part of Brazzaville participated in this study. Blood samples were obtained from all children at enrollment and checked for P. falciparum infection. Based on the one year follow-up data, two clinical groups were considered according to the number of malaria episodes presented over the follow up period: “protected”(children who did not experience any episode) and “unprotected” (those who experienced more that two episodes). Therefore, the msp2 genetic diversity of P. falciparum isolates collected at enrollment in the two groups was characterized by allele-specific nested PCR and compared. The msp2 profiles of P. falciparum isolates collected from successive malaria episodes was also characterized by allele-specific nested PCR. Results Forty-three percent of FC27 and fifty-seven percent of 3D7 in protected vs fifty-six percent of FC27 and forty-four percent of 3D7 in isolates from unprotected children were detected. Seven and two alleles belonging to the FC27, and six and three alleles belonging to 3D7 families were distinguished in isolates from protected and unprotected children respectively. The mean multiplicity of infection (MOI) values at inclusion for the msp2 locus was 1.29 and 1.43 for protected and unprotected children respectively. 43 isolates were obtained from the ten children who had four or more clinical episodes during the follow up. A total of 63 alleles or

  14. 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

  15. 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.

  16. 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.

  17. Demyelination during multiple sclerosis is associated with combined activation of microglia/macrophages by IFN-γ and alpha B-crystallin.

    PubMed

    Bsibsi, Malika; Peferoen, Laura A N; Holtman, Inge R; Nacken, Peter J; Gerritsen, Wouter H; Witte, Maarten E; van Horssen, Jack; Eggen, Bart J L; van der Valk, Paul; Amor, Sandra; van Noort, Johannes M

    2014-08-01

    Activated microglia and macrophages play a key role in driving demyelination during multiple sclerosis (MS), but the factors responsible for their activation remain poorly understood. Here, we present evidence for a dual-trigger role of IFN-γ and alpha B-crystallin (HSPB5) in this context. In MS-affected brain tissue, accumulation of the molecular chaperone HSPB5 by stressed oligodendrocytes is a frequent event. We have shown before that this triggers a TLR2-mediated protective response in surrounding microglia, the molecular signature of which is widespread in normal-appearing brain tissue during MS. Here, we show that IFN-γ, which can be released by infiltrated T cells, changes the protective response of microglia and macrophages to HSPB5 into a robust pro-inflammatory classical response. Exposure of cultured microglia and macrophages to IFN-γ abrogated subsequent IL-10 induction by HSPB5, and strongly promoted HSPB5-triggered release of TNF-α, IL-6, IL-12, IL-1β and reactive oxygen and nitrogen species. In addition, high levels of CXCL9, CXCL10, CXL11, several guanylate-binding proteins and the ubiquitin-like protein FAT10 were induced by combined activation with IFN-γ and HSPB5. As immunohistochemical markers for microglia and macrophages exposed to both IFN-γ and HSPB5, these latter factors were found to be selectively expressed in inflammatory infiltrates in areas of demyelination during MS. In contrast, they were absent from activated microglia in normal-appearing brain tissue. Together, our data suggest that inflammatory demyelination during MS is selectively associated with IFN-γ-induced re-programming of an otherwise protective response of microglia and macrophages to the endogenous TLR2 agonist HSPB5.

  18. XPO1 inhibitor combination therapy with bortezomib or carfilzomib induces nuclear localization of IκBα and overcomes acquired proteasome inhibitor resistance in human multiple myeloma

    PubMed Central

    Turner, Joel G.; Kashyap, Trinayan; Dawson, Jana L.; Gomez, Juan; Bauer, Alexis A.; Grant, Steven; Dai, Yun; Shain, Kenneth H.; Meads, Mark; Landesman, Yosef; Sullivan, Daniel M.

    2016-01-01

    Acquired proteasome-inhibitor (PI) resistance is a major obstacle in the treatment of multiple myeloma (MM). We investigated whether the clinical XPO1-inhibitor selinexor, when combined with bortezomib or carfilzomib, could overcome acquired resistance in MM. PI-resistant myeloma cell lines both in vitro and in vivo and refractory myeloma patient biopsies were treated with selinexor/bortezomib or carfilzomib and assayed for apoptosis. Mechanistic studies included NFκB pathway protein expression assays, immunofluorescence microscopy, ImageStream flow-cytometry, and proximity-ligation assays. IκBα knockdown and NFκB activity were measured in selinexor/bortezomib-treated MM cells. We found that selinexor restored sensitivity of PI-resistant MM to bortezomib and carfilzomib. Selinexor/bortezomib treatment inhibited PI-resistant MM tumor growth and increased survival in mice. Myeloma cells from PI-refractory MM patients were sensitized by selinexor to bortezomib and carfilzomib without affecting non-myeloma cells. Immunofluorescence microscopy, Western blot, and ImageStream analyses of MM cells showed increases in total and nuclear IκBα by selinexor/bortezomib. Proximity ligation found increased IκBα-NFκB complexes in treated MM cells. IκBα knockdown abrogated selinexor/bortezomib-induced cytotoxicity in MM cells. Selinexor/bortezomib treatment decreased NFκB transcriptional activity. Selinexor, when used with bortezomib or carfilzomib, has the potential to overcome PI drug resistance in MM. Sensitization may be due to inactivation of the NFκB pathway by IκBα. PMID:27806331

  19. 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

  20. 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…

  1. 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,…

  2. Analgesic combinations

    PubMed Central

    Raffa, Robert B.; Pergolizzi, Joseph V.; Tallarida, Ronald J.

    2010-01-01

    When the pathophysiology of a medical condition is multi-modal, i.e., related to multiple physiological causes or mediated by multiple pathways, the optimal strategy can be to use a drug or a combination of drugs that contribute multiple mechanisms to the therapeutic endpoint. In such situations, a rational multi-modal approach can also result in the fewest adverse effects. We discuss the quantitative analysis of multi-modal action using the treatment of pain as a practical example and give examples of its application to some widely used analgesic drugs. PMID:20338825

  3. Further stratification of patients with multiple myeloma by International Staging System in combination with ratio of serum free κ to λ light chains.

    PubMed

    Xu, Yan; Sui, Weiwei; Deng, Shuhui; An, Gang; Wang, Yafei; Xie, Zhenqing; Yao, Hongjing; Zhu, Guoqing; Zou, Dehui; Qi, Junyuan; Hao, Mu; Zhao, Yaozhong; Wang, Jianxiang; Chen, Tao; Qiu, Lugui

    2013-01-01

    The serum free light chain (sFlc) levels were measured for 122 Chinese patients with newly diagnosed symptomatic multiple myeloma (NDSMM), and κ/λ ratios (rFlc) were calculated. The data were analyzed for the roles of sFlc and rFlc in the diagnosis and prognosis of MM. Abnormal sFlc and/or rFlc were detected in 99.2% of patients, demonstrating that the FLC assay is much more sensitive than the commonly used methods. Baseline sFlc and rFlc successfully predicted the overall survival (OS). The median OS was not reached (NR) versus 23 months for the low sFLC group (sFLC-κ < 180 mg/L or sFLC-λ < 592.5 mg/L) and high sFLC group (sFLC-κ ≥ 180 mg/L or sFLC-λ ≥ 592.5 mg/L) (p = 0.001), and NR versus 21 months for the low rFLC group (0.04 ≤ rFLC ≤ 25) and high rFLC group (p < 0.001), respectively. Interestingly, the significant differences in OS between the low and high rFLC groups were not changed by bortezomib chemotherapy. In addition, patients were further stratified by three novel poor-prognosis factors (β(2)-microglobulin [β2-MG] > 3.5 mg/L, albumin [ALB] < 35 g/L, rFLC > 25 or rFLC < 0.04) that were developed from combination of the rFlc with the International Staging System (ISS): the low risk group (no factor), the low-intermediate risk group (one factor), the high-intermediate risk group (two factors) and the high risk group (three factors). The median OS for those groups was NR, NR, 24 months and 13 months, respectively (p < 0.05). In conclusion, the sFLC assay was highly sensitive in the diagnosis of MM in Chinese patients. The prognostic potential of the ISS may be improved with the addition of rFLC.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. Effects of Intraluminal Thrombus on Patient-Specific Abdominal Aortic Aneurysm Hemodynamics via Stereoscopic Particle Image Velocity and Computational Fluid Dynamics Modeling

    PubMed Central

    Chen, Chia-Yuan; Antón, Raúl; Hung, Ming-yang; Menon, Prahlad; Finol, Ender A.; Pekkan, Kerem

    2014-01-01

    The pathology of the human abdominal aortic aneurysm (AAA) and its relationship to the later complication of intraluminal thrombus (ILT) formation remains unclear. The hemodynamics in the diseased abdominal aorta are hypothesized to be a key contributor to the formation and growth of ILT. The objective of this investigation is to establish a reliable 3D flow visualization method with corresponding validation tests with high confidence in order to provide insight into the basic hemodynamic features for a better understanding of hemodynamics in AAA pathology and seek potential treatment for AAA diseases. A stereoscopic particle image velocity (PIV) experiment was conducted using transparent patient-specific experimental AAA models (with and without ILT) at three axial planes. Results show that before ILT formation, a 3D vortex was generated in the AAA phantom. This geometry-related vortex was not observed after the formation of ILT, indicating its possible role in the subsequent appearance of ILT in this patient. It may indicate that a longer residence time of recirculated blood flow in the aortic lumen due to this vortex caused sufficient shear-induced platelet activation to develop ILT and maintain uniform flow conditions. Additionally, two computational fluid dynamics (CFD) modeling codes (Fluent and an in-house cardiovascular CFD code) were compared with the two-dimensional, three-component velocity stereoscopic PIV data. Results showed that correlation coefficients of the out-of-plane velocity data between PIV and both CFD methods are greater than 0.85, demonstrating good quantitative agreement. The stereoscopic PIV study can be utilized as test case templates for ongoing efforts in cardiovascular CFD solver development. Likewise, it is envisaged that the patient-specific data may provide a benchmark for further studying hemodynamics of actual AAA, ILT, and their convolution effects under physiological conditions for clinical applications. PMID:24316984

  9. 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…

  10. High-dose-rate intraluminal brachytherapy prior to external radiochemotherapy in locally advanced esophageal cancer: preliminary results

    PubMed Central

    Safaei, Afsaneh Maddah; Ghalehtaki, Reza; Khanjani, Nezhat; Farazmand, Borna; Babaei, Mohammad

    2017-01-01

    Purpose Dysphagia is a common initial presentation in locally advanced esophageal cancer and negatively impacts patient quality of life and treatment compliance. To induce fast relief of dysphagia in patients with potentially operable esophageal cancer high-dose-rate (HDR) brachytherapy was applied prior to definitive radiochemotherapy. Material and methods In this single arm phase II clinical trial between 2013 to 2014 twenty patients with locally advanced esophageal cancer (17 squamous cell and 3 adenocarcinoma) were treated with upfront 10 Gy HDR brachytherapy, followed by 50.4 Gy external beam radiotherapy (EBRT) and concurrent chemotherapy with cisplatin/5-fluorouracil. Results Tumor response, as measured by endoscopy and/or computed tomography scan, revealed complete remission in 16 and partial response in 4 patients (overall response rate 100%). Improvement of dysphagia was induced by brachytherapy within a few days and maintained up to the end of treatment in 80% of patients. No differences in either response rate or dysphagia resolution were found between squamous cell and adenocarcinoma histology. The grade 2 and 3 acute pancytopenia or bicytopenia reported in 4 patients, while sub-acute adverse effects with painful ulceration was seen in five patients, occurring after a median of 2 months. A perforation developed in one patient during the procedure of brachytherapy that resolved successfully with immediate surgery. Conclusions Brachytherapy before EBRT was a safe and effective procedure to induce rapid and durable relief from dysphagia, especially when combined with EBRT. PMID:28344601

  11. Colonic perforation with intraluminal stents and bevacizumab in advanced colorectal cancer: retrospective case series and literature review

    PubMed Central

    Imbulgoda, Amal; MacLean, Anthony; Heine, John; Drolet, Sebastien; Vickers, Michael M.

    2015-01-01

    Background Self-expanding metal stents (SEMS) are increasingly used in the treatment of malignant large bowel obstruction in the setting of inoperable colorectal cancer. Perforation is a well-known complication associated with these devices. The addition of the vascular endothelial growth factor inhibitor bevacizumab is suspected to increase the rate, but the extent of the increase is not known. Methods We retrospectively reviewed the records of patients receiving SEMS in tertiary hospitals in Calgary, Alta., between October 2001 and January 2012. Results We reviewed the records of 87 patients with inoperable colorectal cancer who received SEMS during our study period. Nine perforations occurred in total: 4 of 30 (13%) patients who received no chemotherapy, 3 of 47 (6%) who received chemotherapy but no bevacizumab, and 2 of 10 (20%) who received chemotherapy and bevacizumab. These two patients received bevacizumab with FOLFIRI after SEMS placement, and they had peritoneal disease. Conclusion Our case series and other studies suggest that bevacizumab may increase the risk of colonic perforation in the setting of SEMS. Caution should be used when combining these therapies. PMID:25799132

  12. Hereditary multiple intestinal atresia (HMIA) with severe combined immunodeficiency (SCID): a case report of two siblings and review of the literature on MIA, HMIA and HMIA with immunodeficiency over the last 50 years

    PubMed Central

    Ali, Yasser Ali Hussein; Rahman, Sajjad; Bhat, Venkatraman; Thani, Sheikha Al; Ismail, Adel; Bassiouny, Ibrahim

    2011-01-01

    Hereditary multiple intestinal atresia (HMIA), a presumed autosomal recessive disorder, is an unusual and rare form of recurrent intestinal atresia which can be associated with severe combined immunodeficiency (SCID). The combination of HMIA and SCID is invariably lethal. The authors describe this fatal association in two siblings. The parents are consanguineous and have three other normal healthy children. Both index cases had abnormal antenatal ultrasounds and were symptomatic after birth. The final diagnosis of HMIA with SCID was confirmed in both siblings. They were never able to receive enteral feeds, remained totally dependent on parenteral nutrition, had repeated episodes of sepsis and died after a very difficult neonatal intensive care course. In this article we have reviewed the clinical course and outcome of both cases. The existing literature on multiple intestinal atresia, HMIA and HMIA with immunodeficiency is also reviewed. PMID:22715199

  13. 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.

  14. Multiple neural tube defects: a rare combination of limited dorsal myeloschisis, diplomyelia with dorsal bony spur, sacral meningocoele, syringohydromyelia, and tethered cord.

    PubMed

    Shashank R, Ramdurg; Shubhi, Dubey; Vishal, Kadeli

    2017-04-01

    Multiple neural tube defects are relatively rare. They account for less than 1% reported neural tube defects. Cases of limited dorsal myeloschisis (LDM) and diplomyelia (two cords in single sac without intervening bony or fibrous septae) with dorsal bony spur are also a rare event. Here, the authors report a rare case of neonate with thoracic LDM, diplomyelia with dorsal bony spur, sacral meningocoele with syringohydromyelia, and low-lying tethered cord. The child also had a ventricular septal defect (VSD) and bilateral rocker bottom feet. Various environmental factors and genetic mutations in transmembrane proteins have been studied in animal models explaining the origin of neural tube defects. To the best of author's knowledge, this is the first case of varied multiple neural tube defects with diplomyelia reported in world literature.

  15. Multiple-pressure-tapped core holder combined with X-ray computed tomography scanning for gas-water permeability measurements of methane-hydrate-bearing sediments.

    PubMed

    Konno, Yoshihiro; Jin, Yusuke; Uchiumi, Takashi; Nagao, Jiro

    2013-06-01

    We present a novel setup for measuring the effective gas-water permeability of methane-hydrate-bearing sediments. We developed a core holder with multiple pressure taps for measuring the pressure gradient of the gas and water phases. The gas-water flooding process was simultaneously detected using an X-ray computed tomography scanner. We successfully measured the effective gas-water permeability of an artificial sandy core with methane hydrate during the gas-water flooding test.

  16. 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.

  17. Anti-angiogenic and anti-multiple myeloma effects of oprozomib (OPZ) alone and in combination with pomalidomide (Pom) and/or dexamethasone (Dex).

    PubMed

    Sanchez, Eric; Li, Mingjie; Wang, Cathy S; Tang, George; Gillespie, Abigail; Chen, Haiming; Berenson, James R

    2017-03-06

    Oprozomib (OPZ or ONYX 0912) is an irreversible, orally administered proteasome inhibitor (PI) and an analog of carfilzomib. We set out to determine the anti-angiogenic effect of OPZ using the choriollantoic membrane/feather bud (CAM/FB) model and its anti-MM effects using MM xenograft models (LAGκ-1A, LAGλ-1). OPZ significantly reduced blood vessel formation, endothelial gene and protein expression using the CAM/FB assay. In vivo, we determined the anti-MM effects of OPZ, dexamethasone (Dex) and pomalidomide (Pom) and showed that the combinations of two drugs (OPZ+Dex or OPZ+Pom) showed marked anti-MM effects when compared to monotherapy. Pom+Dex and the triplicate combination (OPZ+Pom+Dex) showed more anti-MM effects when compared to the doublets of either OPZ+Dex or OPZ+Pom; continued treatment with all three drugs (OPZ+Pom+Dex) was superior when compared to Pom+Dex, in both MM xenograft models tested. These studies show that OPZ has anti-angiogenic effects, and that the combination of OPZ, Dex and Pom produces greater anti-MM effects in vivo when compared to any of the doublet combinations. These studies provide further support for clinical trials evaluating OPZ in combination with Pom and Dex.

  18. Regorafenib with a fluoropyrimidine for metastatic colorectal cancer after progression on multiple 5-FU-containing combination therapies and regorafenib monotherapy

    PubMed Central

    Marks, Eric I.; Tan, Carlyn; Zhang, Jun; Zhou, Lanlan; Yang, Zhaohai; Scicchitano, Angelique; El-Deiry, Wafik S.

    2015-01-01

    We present 2 patients with metastatic colorectal cancer who had progressed despite treatment with first-line FOLFOX and second-line FOLFIRI combination chemotherapy regimens. After failing these fluoropyrimidine-based regimens, both patients received additional cytotoxic and targeted therapies with eventual disease progression. These therapies included capecitabine plus dabrafenib and trametinib, regorafenib monotherapy, and regorafenib with panitumumab. After exhausting available options, both patients were offered regorafenib with either 5-fluorouracil (5-FU) or capecitabine. These therapies are individually approved for the treatment of colorectal cancer but have not yet been studied in combination. This regimen produced stable disease in both patients with acceptable toxicity. One patient continued therapy for 17 months. Although these patients previously progressed during treatment with regorafenib, capecitabine or 5-FU, the combination had some activity in both cases of refractory metastatic colorectal cancer and may be considered in the palliative setting. In bedside-to-bench cell culture experiments performed after the clinical observations, we observed sensitivity of human colorectal cancer cell lines (N = 4) to single agent regorafenib or 5-FU and evidence of synergy with the combination therapy. Synergistic effects were noted in colorectal cancer cells with KRAS mutation, BRAF mutation, and p53 mutation, as well as mismatch repair deficient cells. Regorafenib suppressed Mcl-1 and Bcl-XL in treated cancer cells that may have contributed to the anticancer efficacy including in combination with 5-FU. The safety and efficacy of regorafenib with 5-FU or capecitabine in combination should be further investigated as a therapy for patients with refractory metastatic colorectal cancer, including individuals who had progressed on regorafenib monotherapy. PMID:26561209

  19. 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...

  20. Instrumental intelligent test of food sensory quality as mimic of human panel test combining multiple cross-perception sensors and data fusion.

    PubMed

    Ouyang, Qin; Zhao, Jiewen; Chen, Quansheng

    2014-09-02

    Instrumental test of food quality using perception sensors instead of human panel test is attracting massive attention recently. A novel cross-perception multi-sensors data fusion imitating multiple mammal perception was proposed for the instrumental test in this work. First, three mimic sensors of electronic eye, electronic nose and electronic tongue were used in sequence for data acquisition of rice wine samples. Then all data from the three different sensors were preprocessed and merged. Next, three cross-perception variables i.e., color, aroma and taste, were constructed using principal components analysis (PCA) and multiple linear regression (MLR) which were used as the input of models. MLR, back-propagation artificial neural network (BPANN) and support vector machine (SVM) were comparatively used for modeling, and the instrumental test was achieved for the comprehensive quality of samples. Results showed the proposed cross-perception multi-sensors data fusion presented obvious superiority to the traditional data fusion methodologies, also achieved a high correlation coefficient (>90%) with the human panel test results. This work demonstrated that the instrumental test based on the cross-perception multi-sensors data fusion can actually mimic the human test behavior, therefore is of great significance to ensure the quality of products and decrease the loss of the manufacturers.

  1. 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

  2. Predictive thermal inactivation model for the combined effect of temperature, cinnamaldehyde and carvacrol on starvation-stressed multiple Salmonella serotypes in ground chicken.

    PubMed

    Juneja, Vijay K; Gonzales-Barron, Ursula; Butler, Francis; Yadav, Ajit S; Friedman, Mendel

    2013-07-15

    We investigated the combined effect of three internal temperatures (60, 65 and 71.1 °C) 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 (3×4×4) was used to assess the effects and interactions of heating temperature and the two antimicrobials, carvacrol and cinnamaldehyde. The 48 variable combinations were replicated to provide a total of 96 survivor curves from the experimental data. Mathematical models were then developed to quantify the combined effect of these parameters on heat resistance of starved Salmonella cells. The theoretical analysis shows that the addition of plant-derived antimicrobials overcomes the heat resistance of starvation-stressed Salmonella in ground chicken meat. The influence of the antimicrobials allows reduced heat treatments, thus reducing heat-induced damage to the nutritional quality of ground-chicken products. Although the reported omnibus log-linear model with tail and the omnibus sigmoid model could represent the experimental survivor curves, their discrepancy only became apparent in the present study when lethality times (D-values and t7.0) from each of the models were calculated. Given the concave nature of the inactivation curves, the log-linear model with tail greatly underestimates the times needed to obtain 7.0 log lethality. Thus, a polynomial secondary model, based on the sigmoid model, was developed to accurately predict the 7.0-log reduction times. The three-factor predictive model can be used to estimate the processing times and temperatures required to achieve specific log reductions, including the regulatory recommendation of 7.0-log reduction of Salmonella in ground chicken.

  3. 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

    2015-12-04

    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

  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. 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

  6. 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

  7. 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.

  8. Exploring pyrazolo[3,4-d]pyrimidine phosphodiesterase 1 (PDE1) inhibitors: a predictive approach combining comparative validated multiple molecular modelling techniques.

    PubMed

    Amin, Sk Abdul; Bhargava, Sonam; Adhikari, Nilanjan; Gayen, Shovanlal; Jha, Tarun

    2017-02-13

    Phosphodiesterase 1 (PDE1) is a potential target for a number of neurodegenerative disorders such as Schizophrenia, Parkinson's and Alzheimer's diseases. A number of pyrazolo[3,4-d]pyrimidine PDE1 inhibitors were subjected to different molecular modelling techniques [such as regression-based quantitative structure-activity relationship (QSAR): multiple linear regression, support vector machine and artificial neural network; classification-based QSAR: Bayesian modelling and Recursive partitioning; Monte Carlo based QSAR; Open3DQSAR; pharmacophore mapping and molecular docking analyses] to get a detailed knowledge about the physicochemical and structural requirements for higher inhibitory activity. The planarity of the pyrimidinone ring plays an important role for PDE1 inhibition. The N-methylated function at the 5th position of the pyrazolo[3,4-d]pyrimidine core is required for interacting with the PDE1 enzyme. The cyclopentyl ring fused with the parent scaffold is necessary for PDE1 binding potency. The phenylamino substitution at 3rd position is crucial for PDE1 inhibition. The N2-substitution at the pyrazole moiety is important for PDE1 inhibition compared to the N1-substituted analogues. Moreover, the p-substituted benzyl side chain at N2-position helps to enhance the PDE1 inhibitory profile. Depending on these observations, some new molecules are predicted that may possess better PDE1 inhibition.

  9. Cellular VPS4 Is Required for Efficient Entry and Egress of Budded Virions of Autographa californica Multiple Nucleopolyhedrovirus

    PubMed Central

    Li, Zhaofei

    2012-01-01

    Membrane budding is essential for the egress of many enveloped viruses, and this process shares similarities with the biogenesis of multivesicular bodies (MVBs). In eukaryotic cells, the budding of intraluminal vesicles (IVLs) is mediated by the endosomal sorting complex required for transport (ESCRT) machinery and some viruses require ESCRT machinery components or functions to bud from host cells. Baculoviruses, such as Autographa californica multiple nucleopolyhedrovirus (AcMNPV), enter host cells by clathrin-mediated endocytosis. Viral DNA replication and nucleocapsid assembly occur within the nucleus. Some progeny nucleocapsids are subsequently trafficked to, and bud from, the plasma membrane, forming budded virions (BV). To determine whether the host ESCRT machinery is important or necessary for AcMNPV replication, we cloned a cDNA of Spodoptera frugiperda VPS4, a key regulator for disassembly and recycling of ESCRT III. We then examined viral infection and budding in the presence of wild-type (WT) or dominant negative (DN) forms of VPS4. First, we used a viral complementation system, in combination with fluorescent tags, to examine the effects of transiently expressed WT or DN VPS4 on viral entry. We found that dominant negative VPS4 substantially inhibited virus entry. Entering virus was observed within aberrant compartments containing the DN VPS4 protein. We next used recombinant bacmids expressing WT or DN VPS4 proteins to examine virus egress. We found that production of infectious AcMNPV BV was substantially reduced by expression of DN VPS4 but not by WT VPS4. Together, these results indicate that a functional VPS4 is necessary for efficient AcMNPV BV entry into, and egress from, insect cells. PMID:22072775

  10. Combined chemical (fluoranthene) and drought effects on Lumbricus rubellus demonstrate the applicability of the independent action model for multiple stressor assessment.

    PubMed

    Long, Sara M; Reichenberg, Fredrik; Lister, Lindsay J; Hankard, Peter K; Townsend, Joanna; Mayer, Philipp; Wright, Julian; Holmstrup, Martin; Svendsen, Claus; Spurgeon, David J

    2009-03-01

    The combined effect of a chemical (fluoranthene) and a nonchemical stress (reduced soil moisture content) to the widely distributed earthworm Lumbricus rubellus were investigated in a laboratory study. Neither fluoranthene (up to 500 microg/g) nor low soil moisture (15% below optimal) had a significant effect on the survival of the exposed worms, but a significant effect on reproduction (cocoon production rate) was found for both stressors (p < 0.001 in both cases). The response of cocoon production to each stressor could be well described by a logistic model; this suggested that the joint effects may be applicable to description using the independent action (IA) model that is widely used in pharmacology and chemical mixture risk assessment. Fitting of the IA model provided a good description of the combined stressor data (accounting for 53.7% of total variation) and was the most parsimonious model describing joint effect (i.e., the description of the data was not improved by addition of further parameters accounting for synergism or antagonism). Thus, the independent action of the two responses was further supported by measurement of internal fluoranthene exposure. The chemical activity of fluoranthene in worm tissue was correlated only with soil fluoranthene concentration and not with soil moisture content. Taken together these results suggest that the IA model can help interpret the joint effects of chemical and nonchemical stressors. Such analyses should, however, be done with caution since the literature data set suggests that there may be cases where interactions between stressors result in joint effects that differ significantly from IA predictions.

  11. 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

  12. 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

  13. Identification of multiple constituents in Chinese medicinal prescription Shensong Yangxin capsule by ultra-fast liquid chromatography combined with quadrupole time-of-flight mass spectrometry.

    PubMed

    Liu, Minyan; Zhao, Shaohua; Wang, Yufeng; Liu, Ting; Li, Song; Wang, Hongtao; Tu, Pengfei

    2015-02-01

    A practical method using ultra-fast liquid chromatography in tandem with quadrupole time-of-flight mass spectrometry combined with dynamic background subtraction technology was developed for the rapid separation and identification of the complicated constituents in the Shensong Yangxin capsule (SSYX). The chromatographic separation was performed on a C18 column (2.1 × 100 mm, 2.6 μm) with a gradient elution program using methanol and 0.1% formic acid aqueous solution as the mobile phase at a flow rate of 0.4 mL min(-1). Accurate mass measurements of the molecular ions in the full scan and the characteristic fragment ions triggered by information-dependent acquisition provided reliable identification criteria. Thus, 99 compounds, including saponins, phenolic acids, tanshinones, lignans, terpenoids, alkaloids and flavonoids, were unambiguously or tentatively identified in 40 min by comparing their retention times and accurate mass measurements for each molecular ion and its subsequent fragment ions with those of authentic standards or literature data. Simultaneously, all the compounds were further assigned to the individual raw materials. In conclusion, these results will provide a basis for quality control and further study of SSYX, and the proposed technique based on high-resolution mass spectrometry would be expected to be adaptable to the analysis of complicated constituents in various complex matrices.

  14. High-throughput screening to estimate single or multiple enzymes involved in drug metabolism: microtitre plate assay using a combination of recombinant CYP2D6 and human liver microsomes.

    PubMed

    Yamamoto, T; Suzuki, A; Kohno, Y

    2003-08-01

    1. The purpose of this study was to estimate readily involvement of single or multiple enzymes in the metabolism of a drug through inhibitory assessment. Inhibitory effects of various compounds on CYP2D6 activity assayed by formation of fluorescent metabolite from 3-[2-(N,N-diethyl-N-methyl-ammonium)ethyl]-7-methoxy-4-methyl-coumarin (AMMC) were assessed using microtitre plate (MTP) assays with a combination of recombinant CYP2D6 and human liver microsomes (HLM). 2. Among various compounds studied, antipsychotic drugs extensively inhibited recombinant CYP2D6 activity and the IC50 values were generally lower than those of antidepressants and antiarrhythmic drugs. 3. After pre-incubation, the IC50 values of mianserin, chlorpromadine, risperidone, thioridazine, alprenolol, propafenone and dextromethorphan increased but the values of timolol, S-metoprolol and propranolol substantially decreased compared with those in case of co-incubation. 4. The IC50 values of typical substrates of CYP2D6 (bufuralol and dextromethorphan at lower substrate concentration) in inhibition studies using HLM, were similar to those in the case of recombinant CYP2D6, but the values of the compounds that are metabolized by multiple CYP forms (perphenazine and chlorpromazine) in HLM were much larger. 5. If the ratio (HLM/rCYP ratio) of IC50 values between HLM and recombinant CYP2D6 exceeds approximately 2, it suggests that other CYP forms in addition to CYP2D6 might be involved in the metabolism of the test compounds. From the advantage such as speed, high throughput and ease of the technique, the MTP assay using a combination of the recombinant CYP2D6 and HLM is useful to estimate the involvement of single or multiple enzymes in the metabolism of drugs at the stage of drug discovery.

  15. Polygenic Control of Carotid Atherosclerosis in a BALB/cJ × SM/J Intercross and a Combined Cross Involving Multiple Mouse Strains

    PubMed Central

    Grainger, Andrew T.; Jones, Michael B.; Chen, Mei-Hua; Shi, Weibin

    2016-01-01

    Atherosclerosis in the carotid arteries is a major cause of ischemic stroke, which accounts for 85% of all stroke cases. Genetic factors contributing to carotid atherosclerosis remain poorly understood. The aim of this study was to identify chromosomal regions harboring genes contributing to carotid atherosclerosis in mice. From an intercross between BALB/cJ (BALB) and SM/J (SM) apolipoprotein E-deficient (Apoe−/−) mice, 228 female F2 mice were generated and fed a “Western” diet for 12 wk. Atherosclerotic lesion sizes in the left carotid artery were quantified. Across the entire genome, 149 genetic markers were genotyped. Quantitative trait locus (QTL) analysis revealed eight loci for carotid lesion sizes, located on chromosomes 1, 5, 12, 13, 15, 16, and 18. Combined cross-linkage analysis using data from this cross, and two previous F2 crosses derived from BALB, C57BL/6J and C3H/HeJ strains, identified five significant QTL on chromosomes 5, 9, 12, and 13, and nine suggestive QTL for carotid atherosclerosis. Of them, the QTL on chromosome 12 had a high LOD score of 9.95. Bioinformatic analysis prioritized Arhgap5, Akap6, Mipol1, Clec14a, Fancm, Nin, Dact1, Rtn1, and Slc38a6 as probable candidate genes for this QTL. Atherosclerotic lesion sizes were significantly correlated with non-HDL cholesterol levels (r = 0.254; p = 0.00016) but inversely correlated with HDL cholesterol levels (r = −0.134; p = 0.049) in the current cross. Thus, we demonstrated the polygenic control of carotid atherosclerosis in mice. The correlations of carotid lesion sizes with non-HDL and HDL suggest that genetic factors exert effects on carotid atherosclerosis partially through modulation of lipoprotein homeostasis. PMID:28040783

  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).

  17. 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

  18. 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

    SciTech Connect

    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 only be understood by probing the structure at the relevant length scales.

  19. 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

  20. 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

    2016-01-05

    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.

  1. Multiple Sclerosis

    MedlinePlus

    Multiple sclerosis Overview By Mayo Clinic Staff Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord (central nervous system). In MS, the immune system attacks the protective ...

  2. 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 ...

  3. 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 ...

  4. Rapid detection and identification of N-acetyl-L-cysteine thioethers using constant neutral loss and theoretical multiple reaction monitoring combined with enhanced product-ion scans on a linear ion trap mass spectrometer.

    PubMed

    Scholz, Karoline; Dekant, Wolfgang; Völkel, Wolfgang; Pähler, Axel

    2005-12-01

    A sensitive and specific liquid chromatography-mass spectrometry (LC-MS) method based on the combination of constant neutral loss scans (CNL) with product ion scans was developed on a linear ion trap. The method is applicable for the detection and identification of analytes with identical chemical substructures (such as conjugates of xenobiotics formed in biological systems) which give common CNLs. A specific CNL was observed for thioethers of N-acetyl-L-cysteine (mercapturic acids, MA) by LC-MS/MS. MS and HPLC parameters were optimized with 16 MAs available as reference compounds. All of these provided a CNL of 129 Da in the negative-ion mode. To assess sensitivity, a multiple reaction monitoring (MRM) mode with 251 theoretical transitions using the CNL of 129 Da combined with a product ion scan (IDA thMRM) was compared with CNL combined with a product ion scan (IDA CNL). An information-dependent acquisition (IDA) uses a survey scan such as MRM (multiple reaction monitoring) to generate "informations" and starting a second acquisition experiment such as a product ion scan using these "informations." Th-MRM means calculated transitions and not transitions generated from an available standard in the tuning mode. The product ion spectra provide additional information on the chemical structure of the unknown analytes. All MA standards were spiked in low concentrations to rat urines and were detected with both methods with LODs ranging from 60 pmol/mL to 1.63 nmol/mL with IDA thMRM. The expected product ion spectra were observed in urine. Application of this screening method to biological samples indicated the presence of a number of MAs in urine of unexposed rats, and resulted in the identification of 1,4-dihydroxynonene mercapturic acid as one of these MAs by negative and positive product ion spectra. These results show that the developed methods have a high potential to serve as both a prescreen to detect unknown MAs and to identify these analytes in complex matrix.

  5. 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.

  6. 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.

  7. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study

    PubMed Central

    O'Sullivan, Amy; Kennedy, Ryan C.; Abbas, Mohammad; Dai, Lijun; Pregja, Silvana Lalo; Burt, Steve; Boyiadzis, Michael; Roodman, G. David; Mapara, Markus Y.; Agha, Mounzer; Waas, John; Shuai, Yongli; Normolle, Daniel; Zonder, Jeffrey A.

    2012-01-01

    This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 evaluable patients were enrolled. Median age was 63 years (range, 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m2 (days 1 and 2), lenalidomide 10 mg (days 1-21), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. This study is registered at www.clinicaltrials.gov as #NCT01042704. PMID:22451423

  8. 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.

  9. A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2.

    PubMed

    Lavik, Andrew R; Zhong, Fei; Chang, Ming-Jin; Greenberg, Edward; Choudhary, Yuvraj; Smith, Mitchell R; McColl, Karen S; Pink, John; Reu, Frederic J; Matsuyama, Shigemi; Distelhorst, Clark W

    2015-09-29

    Bcl-2 inhibits apoptosis by two distinct mechanisms but only one is targeted to treat Bcl-2-positive malignancies. In this mechanism, the BH1-3 domains of Bcl-2 form a hydrophobic pocket, binding and inhibiting pro-apoptotic proteins, including Bim. In the other mechanism, the BH4 domain mediates interaction of Bcl-2 with inositol 1,4, 5-trisphosphate receptors (IP3Rs), inhibiting pro-apoptotic Ca2+ signals. The current anti-Bcl-2 agents, ABT-263 (Navitoclax) and ABT-199 (Venetoclax), induce apoptosis by displacing pro-apoptotic proteins from the hydrophobic pocket, but do not inhibit Bcl-2-IP3R interaction. Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP3 Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP3R interaction and thus inducing Ca2+-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton's tyrosine kinase inhibitor Ibrutinib. Moreover, combining BIRD-2 with ABT-263 or ABT-199 enhances apoptosis induction compared to single agent treatment. Overall, these findings provide strong rationale for developing novel therapeutic agents that mimic the action of BIRD-2 in targeting the BH4 domain of Bcl-2 and disrupting Bcl-2-IP3R interaction.

  10. The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females.

    PubMed

    Paradela, Eduardo R; Alves-Leon, Soniza V; Figueiredo, André L S; Pereira, Valéria C S R; Malfetano, Fabíola; Mansur, Letícia F; Scherpenhuijzen, Simone; Agostinho, Luciana A; Rocha, Catielly F; Rueda-Lopes, Fernanda; Gasparetto, Emerson; Paiva, Carmen L A

    2015-04-01

    The objective of this study was to investigate the association between the HLA alleles at the DQA1, DQB1 and DRB1 loci, the CIITA genetic polymorphisms -168A/G and +1614G/C, and susceptibility to multiple sclerosis (MS) in a sample from Rio de Janeiro State, Brazil. Furthermore, we wished to determine whether any of these associations might be more significant in women compared with men. DNA samples from 52 relapsing-remitting MS (RRMS) patients and 126 healthy controls matched for sex and age were analyzed. We identified a significant HLA-DRB1*15:01-MS association that was female-specific (Odds Ratio (OR) = 4.78; p = 0.001). Furthermore, we observed that the +1614G/C mutation in combination with the HLA-DRB1*15:01 allele increased susceptibility to MS in females (OR = 4.55; p = 0.01). Together, these findings highlight the polygenic nature of MS.

  11. Multiple myeloma.

    PubMed

    Peller, Patrick J

    2015-04-01

    This article presents a review of multiple myeloma, precursor states, and related plasma cell disorders. The clinical roles of fluorodeoxyglucose PET/computed tomography (CT) and the potential to improve the management of patients with multiple myeloma are discussed. The clinical and research data supporting the utility of PET/CT use in evaluating myeloma and other plasma cell dyscrasias continues to grow.

  12. 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

  13. A study on the effects of inhibition of prostaglandin biosynthesis with flunixin meglumine and later administration of prostaglandin F2 alpha on the intraluminal pressure variations in the isthmus of the oviduct in unrestrained gilts.

    PubMed

    Pettersson, A; Einarsson, S; Kindahl, H

    1993-01-01

    Three gilts were each equipped with 2 ultra-miniature pressure sensors, placed at 2 different points along the same isthmus of the oviduct. Following base recordings of isthmic intraluminal pressure, the gilts were treated with 2.2 mg flunixin meglumine (FM) per kg body weight. After FM treatment, the peripheral plasma levels of 15-ketodihydro-PGF2 alpha, the major metabolite of prostaglandin F2 alpha (PGF2 alpha), decreased within 30 min. The frequency of the phasic pressure fluctuations in the isthmus of the oviduct decreased after FM treatment. Exogenous administration of PGF2 alpha increased the peripheral plasma levels of 15-ketodihydro-PGF2 alpha. When administered at a dose of 0.1 mg, PGF2 alpha produced an increase in the frequency of the phasic pressure fluctuations in the oviductal isthmus. When the PGF2 alpha dose was increased to 0.5 mg, a marked increase in the base and total pressures was seen in addition to the increase in the frequency of the phasic pressure fluctuations.

  14. Multiple frame cluster tracking

    NASA Astrophysics Data System (ADS)

    Gadaleta, Sabino; Klusman, Mike; Poore, Aubrey; Slocumb, Benjamin J.

    2002-08-01

    Tracking large number of closely spaced objects is a challenging problem for any tracking system. In missile defense systems, countermeasures in the form of debris, chaff, spent fuel, and balloons can overwhelm tracking systems that track only individual objects. Thus, tracking these groups or clusters of objects followed by transitions to individual object tracking (if and when individual objects separate from the groups) is a necessary capability for a robust and real-time tracking system. The objectives of this paper are to describe the group tracking problem in the context of multiple frame target tracking and to formulate a general assignment problem for the multiple frame cluster/group tracking problem. The proposed approach forms multiple clustering hypotheses on each frame of data and base individual frame clustering decisions on the information from multiple frames of data in much the same way that MFA or MHT work for individual object tracking. The formulation of the assignment problem for resolved object tracking and candidate clustering methods for use in multiple frame cluster tracking are briefly reviewed. Then, three different formulations are presented for the combination of multiple clustering hypotheses on each frame of data and the multiple frame assignments of clusters between frames.

  15. Parenting Multiples

    MedlinePlus

    ... parents. It's important for caretakers to spend time speaking directly to each child, as well as reading to them and encouraging language. Social skills can come earlier for multiples, simply because they' ...

  16. [Multiple meningiomas].

    PubMed

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs.

  17. 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

  18. Combination therapeutics in complex diseases.

    PubMed

    He, Bing; Lu, Cheng; Zheng, Guang; He, Xiaojuan; Wang, Maolin; Chen, Gao; Zhang, Ge; Lu, Aiping

    2016-12-01

    The biological redundancies in molecular networks of complex diseases limit the efficacy of many single drug therapies. Combination therapeutics, as a common therapeutic method, involve pharmacological intervention using several drugs that interact with multiple targets in the molecular networks of diseases and may achieve better efficacy and/or less toxicity than monotherapy in practice. The development of combination therapeutics is complicated by several critical issues, including identifying multiple targets, targeting strategies and the drug combination. This review summarizes the current achievements in combination therapeutics, with a particular emphasis on the efforts to develop combination therapeutics for complex diseases.

  19. The pharmacokinetic screening of multiple components of the Nao Mai Tong formula in rat plasma by liquid chromatography tandem mass spectrometry combined with pattern recognition method and its application to comparative pharmacokinetics.

    PubMed

    Wu, Chunwei; Zhao, Lu; Rong, Yueying; Zhu, Guoxue; Liang, Shengwang; Wang, Shumei

    2016-11-30

    The Nao Mai Tong formula (NMT) is composed of Rhubarb, Ginseng, Ligusticum wallichii and Pueraria in a ratio of 3:3:2:2 (w/w) and is a well-known traditional Chinese prescription that has been clinically employed for treating ischemia cerebrovascular disease. The goal of this study was to investigate the pharmacokinetics of multiple components (chryohol-8-O-β-D-glucoyroide, physcion-8-O-β-D-glucopyranoside, aloe-emodin, rhein, emodin, chrysophanol, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rc, senkyunolide I, ligustilide puerarin, daidzein, 3'-methoxy puerarin) after the oral administration of the NMT formula in rats. A rapid and sensitive UHPLC-Quadrupole-Orbitrap-MS with a sequential positive and negative ionization mode was developed to determine the 15 absorbed ingredients. After extraction from blood, the analytes and internal standards were subjected to ultra-high performance liquid chromatography with Agela Venusil MPC18 (2.1mm×100mm, 3μm, Agela, USA). The mobile phase consisted of methanol and ammonium acetate (3mmolL(-1)) under gradient elution conditions. This validated method was successfully applied to a comparative pharmacokinetic study of fifteen components in rat plasma after oral administration of the NMT formula or single herb extracts to normal and stroke-afflicted rats. A principal component analysis (PCA) was utilized to evaluate the differences in the pharmacokinetic behavior (time-course) of the absorbed components of NMT, and the absorbed components were assigned to 3 separate clusters. A comparison of the body dynamics of each group indicated that cluster B (ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rc) might be the most important constituents controlling the pharmacological effects of NMT. The comparative pharmacokinetic study showed that the different groups had different pharmacokinetic characteristics. The pharmacokinetics-based UHPLC Quadrupole-Orbitrap-MS using a full-scan mode combined

  20. Comparison of diagnostic and therapeutic value of transesophageal echocardiography, intravascular ultrasonic imaging, and intraluminal phased-array imaging in aortic dissection with tear in the descending thoracic aorta (type B).

    PubMed

    Bartel, Thomas; Eggebrecht, Holger; Müller, Silvana; Gutersohn, Achim; Bonatti, Johannes; Pachinger, Otmar; Erbel, Raimund

    2007-01-15

    Transesophageal echocardiography (TEE) and conventional intravascular ultrasound (IVUS) have limited capabilities in type B aortic dissection. To evaluate its diagnostic value, intraluminal phased-array imaging (IPAI) was compared with IVUS and TEE. In 23 patients with type B aortic dissection, IPAI was tested with respect to its ability to depict true lumen (TL) and false lumen (FL), to localize which abdominal arteries originate from the TL and FL, and to identify all entries and reentries. After the completion of TEE, 2 additional examiners performed angiography and positioned an AcuNav catheter inside the TL. An IVUS catheter was then introduced into the TL by a fourth examiner. All examiners were blinded to one another. Four additional patients with type B aortic dissection developed peripheral malperfusion due to TL collapse. Transvenous IPAI was used to guide emergency fenestration of the intimal flap. TL and FL could be equally well identified by all diagnostic methods. IPAI detected more entries than IVUS (3.0 +/- 1.2 vs 0.8 +/- 0.5, p <0.001), and thoracic IPAI depicted more entries than TEE (1.8 +/- 1.0 vs 1.2 +/- 0.5, p <0.001). IPAI and IVUS showed >90% of the abdominal side branches. In all patients with peripheral malperfusion, successful emergency intimal flap fenestration was safely guided by IPAI. In conclusion, in the detailed diagnostic evaluation of type B aortic dissection, IPAI is superior to IVUS and TEE in detecting communications between the TL and FL. IPAI is also highly useful as a guiding tool for emergency intimal flap fenestration.

  1. Finger Multiplication

    ERIC Educational Resources Information Center

    Holmes, Bill

    2010-01-01

    The author has been prompted to write this article about finger multiplication for a number of reasons. Firstly there are a number of related articles in past issues of "Mathematics Teaching" ("MT") which have connections to this algorithm. Secondly, very few of his primary teaching students and professional colleagues appear to be aware of the…

  2. 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…

  3. Multiple Intelligences.

    ERIC Educational Resources Information Center

    Laughlin, Janet

    1999-01-01

    Details the characteristics of Howard Gardner's seven multiple intelligences (MI): linguistic, logical-mathematical, bodily-kinesthetic, spatial, musical, interpersonal, and intrapersonal. Discusses the implications of MI for instruction. Explores how students can study using their preferred learning style - visual, auditory, and physical study…

  4. 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.

  5. 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.

  6. Multiple sclerosis.

    PubMed

    Files, Daniel Kane; Jausurawong, Tani; Katrajian, Ruba; Danoff, Robert

    2015-06-01

    Multiple sclerosis (MS) is a chronic, debilitating disease that can have devastating effects. Presentation varies widely in symptoms, pace, and progression. In addition to a thorough history and physical examination, diagnostic tools required to diagnose MS and exclude other diagnoses include MRI, evoked potential testing, and cerebrospinal fluid analysis. Although the disease is not curable presently, quality of life can be improved by minimizing the frequency and severity of disease burden. Disease modification, symptom management, preservation of function, and treatment of psychosocial issues are paramount to enhance the quality of life for the patient affected with MS.

  7. 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

  8. Multiple Inflation

    NASA Astrophysics Data System (ADS)

    Murphy, Philip Joseph

    1987-09-01

    The Theory of Inflation, namely, that at some point the entropy content of the universe was greatly increased, has much promise. It may solve the puzzles of homogeneity and the creation of structure. However, no particle physics model has yet been found that can successfully drive inflation. The difficulty in satisfying the constraint that the isotropy of the microwave background places on the effective potential of prospective models is immense. In this work we have codified the requirements of such models in a most general form. We have carefully calculated the amounts of inflation the various problems of the Standard Model need for their solution. We have derived a completely model independent upper bound on the inflationary Hubble parameter. We have developed a general notation with which to probe the possibilities of Multiple Inflation. We have shown that only in very unlikely circumstances will any evidence of an earlier inflation, survive the de Sitter period of its successor. In particular, it is demonstrated that it is most unlikely that two bouts of inflation will yield high amplitudes of density perturbations on small scales and low amplitudes on large. We conclude that, while multiple inflation will be of great theoretical interest, it is unlikely to have any observational impact.

  9. Multiple protein structure alignment.

    PubMed Central

    Taylor, W. R.; Flores, T. P.; Orengo, C. A.

    1994-01-01

    A method was developed to compare protein structures and to combine them into a multiple structure consensus. Previous methods of multiple structure comparison have only concatenated pairwise alignments or produced a consensus structure by averaging coordinate sets. The current method is a fusion of the fast structure comparison program SSAP and the multiple sequence alignment program MULTAL. As in MULTAL, structures are progressively combined, producing intermediate consensus structures that are compared directly to each other and all remaining single structures. This leads to a hierarchic "condensation," continually evaluated in the light of the emerging conserved core regions. Following the SSAP approach, all interatomic vectors were retained with well-conserved regions distinguished by coherent vector bundles (the structural equivalent of a conserved sequence position). Each bundle of vectors is summarized by a resultant, whereas vector coherence is captured in an error term, which is the only distinction between conserved and variable positions. Resultant vectors are used directly in the comparison, which is weighted by their error values, giving greater importance to the matching of conserved positions. The resultant vectors and their errors can also be used directly in molecular modeling. Applications of the method were assessed by the quality of the resulting sequence alignments, phylogenetic tree construction, and databank scanning with the consensus. Visual assessment of the structural superpositions and consensus structure for various well-characterized families confirmed that the consensus had identified a reasonable core. PMID:7849601

  10. [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.

  11. Robotic Male Vas Deferens Intraluminal Injection System

    DTIC Science & Technology

    2001-10-25

    controls an electro-mechanical device which assists the medical personnel’s hand holding the injection syringe to approach the biological structure... contraception . The system may be adapted for injection into blood vessels. Key Words: Injection; multimodal imaging; feedback electro-mechanical...based piston drive does not give the necessary "feel" required for correct injection. The force involved in free hand drive of the syringe piston

  12. Power combiner

    DOEpatents

    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.

  13. Multiple osteochondromas

    PubMed Central

    Bovée, Judith VMG

    2008-01-01

    Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1). Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are pedunculated or sessile (broad base) and can vary widely in size. The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15–18. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected. Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal. The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5–5%. MO is an autosomal dominant disorder and is genetically heterogeneous. In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found. The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization. The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas. If the exact mutation is known antenatal diagnosis is technically possible. MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints. Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma. Patients should be well instructed and regular follow-up for early detection

  14. Combination strategies for pain management.

    PubMed

    Raffa, Robert B; Clark-Vetri, Rachel; Tallarida, Ronald J; Wertheimer, Albert I

    2003-10-01

    At least two factors relating to pain management using oral analgesics suggest that combination strategies merit consideration: many pains arise from more than one physiological cause and current analgesics have adverse effect profiles that might be reduced by combination with another agent in smaller doses or with less frequent dosing. In addition to increased convenience, combinations sometimes also result in the unexpected benefit of synergy. But not all pains, clinical settings or combinations merit the extra expense or other potential negative features of fixed-ratio products. This review examines the multiple basic science, clinical and pharmacoeconomic issues relating to analgesic combinations and the methodologies available for assessing these issues.

  15. Detection of multiple steroidal compounds in synthetic urine using comprehensive gas chromatography-mass spectrometry (GC×GC-MS) combined with a molecularly imprinted polymer clean-up protocol.

    PubMed

    Zulfiqar, Adnan; Morgan, Geraint; Turner, Nicholas W

    2014-10-07

    A method capable of screening for multiple steroids in urine has been developed, using a series of twelve structurally similar, and commercially relevant compounds as target analytes. A molecularly imprinted solid phase extraction clean-up step was used to make the sample suitable for injection onto a GC×GC-MS setup. Significant improvements compared to a commercially available C-18 material were observed. Each individual steroid was able to be separated and identified, using both the retention profile and diagnostic fragmentation ion monitoring abilities of the comprehensive chromatographic-mass spectrometry method. Effective LODs of between 11.7 and 27.0 pg were calculated for individual steroids, effectively equivalent to concentration levels of between 0.234 and 0.540 ng mL(-1) in urine, while the application of multiple screen was demonstrated using a 10 ng mL(-1) mixed sample. The nature of this study also removes the need for sample derivitisation which speeds up the screening process.

  16. [Combination chemotherapy composed of mFOLFOX 6, FOLFIRI 2 and surgery and radiation therapy for locoregional recurrences and multiple lung metastases from rectal cancer--a case report].

    PubMed

    Kubo, Hidefumi; Kitahara, Masahiro; Kanekiyo, Shinsuke; Tada, Kosuke; Katayama, Setsu

    2008-07-01

    A 61-year-old man underwent amputation of the rectum for advanced lower rectal cancer in April 2005. UFT-E granules were administered orally daily at 400 mg/body/day following surgery. He developed perineal pain and perineal discharges following an increase the CEA level in April 2006. PET revealed a tumor in the perineum and multiple lung metastases. Chemotherapy with mFOLFOX 6 for 8 courses and FOLFIRI 2 for 4 courses were administered since July in 2006. Although CT revealed a the reduction in multiple lung metastases, CEA was increased to over a maximum 109, high fever continued and the pinealtumor was enlarged in December 2006. The patient underwent resection of the perinealmass, but he developed perinealsevere pain and perinealdischarge. So radiotherapy of the pelvic region was given at a total dose of 40 Gy(given 2 Gy each fragment)followed by administration of FOLFIRI 2 for 12 courses. After chemoradiotherapy, the CEA level was remarkably decreased. PET could not detect any mass in lung fields and revealed a little accumulation in the pelvic region. Chemotherapy with FOLFIRI 2 is administered monthly now, and the CEA level has been within the normal range since July of 2007. The pineal pain and pineal discharge disappeared, so the quality of life has improved dramatically.

  17. 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.

  18. 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 ...

  19. 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.

  20. 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…

  1. 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.

  2. Congenital solitary kidney with multiple renal arteries: case report using MDCT angiography.

    PubMed

    Matusz, Petru; Miclăuş, Graţian Dragoslav; Banciu, Christian Dragoş; Sas, Ioan; Joseph, Shamfa C; Pirtea, Laurenţiu Cornel; Tubbs, R Shane; Loukas, Marios

    2015-01-01

    A congenital solitary kidney with multiple renal arteries is a rare congenital abnormality that can occur in the presence of multiple other anomalies. We describe an atypical case of a right congenital solitary kidney with three renal arteries (RA) one main RA and two additional renal arteries in a 75-year-old woman with uterine didelphys. The main RA had an intraluminal diameter larger than the diameter of the additional renal arteries (AdRAs) at the origin (0.53 cm for the main RA; 0.49 cm and 0.32 cm for the two AdRAs). Both the AdRAs had a greater length than the main RA (3.51 cm for the main RA; 3.70 cm and 4.77 cm for the two AdRAs). The calculated volume of the kidney was 283 cm³, while the volume of the renal parenchyma was 258 cm³. Knowledge of this variant is extremely important in clinical practice as it has been found to be associated with proteinuria, hypertension and renal insufficiency.

  3. 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.

  4. Efficacy of Zofenopril vs. Irbesartan in Combination with a Thiazide Diuretic in Hypertensive Patients with Multiple Risk Factors not Controlled by a Previous Monotherapy: A Review of the Double-Blind, Randomized "Z" Studies.

    PubMed

    Omboni, Stefano; Malacco, Ettore; Napoli, Claudio; Modesti, Pietro Amedeo; Manolis, Athanasios; Parati, Gianfranco; Agabiti-Rosei, Enrico; Borghi, Claudio

    2017-04-01

    Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) are among the recommended treatments for hypertensive patients uncontrolled by monotherapy. Four randomized, double-blind, parallel group studies with a similar design, including 1469 hypertensive patients uncontrolled by a previous monotherapy and with ≥1 cardiovascular risk factor, compared the efficacy of a combination of a sulfhydryl ACE inhibitor (zofenopril at 30 or 60 mg) or an ARB (irbesartan at 150 or 300 mg) plus HCTZ 12.5 mg. The extent of blood pressure (BP)-lowering was assessed in the office and over 24 h. Pleiotropic features of the treatments were evaluated by studying their effect on systemic inflammation, organ damage, arterial stiffness, and metabolic biochemical parameters. Both treatments similarly reduced office and ambulatory BPs after 18-24 weeks. In the ZODIAC study a larger reduction in high sensitivity C reactive protein (hs-CRP) was observed under zofenopril (-0.52 vs. +0.97 mg/dL under irbesartan, p = 0.001), suggesting a potential protective effect against the development of atherosclerosis. In the ZENITH study the rate of carotid plaque regression was significantly larger under zofenopril (32% vs. 16%; p = 0.047). In the diabetic patients of the ZAMES study, no adverse effects of treatments on blood glucose and lipids as well as an improvement of renal function were observed. In patients with isolated systolic hypertension of the ZEUS study, a slight and similar improvement in renal function and small reductions in pulse wave velocity (PWV), augmentation index (AI), and central systolic BP were documented with both treatments. Thus, the fixed combination of zofenopril and HCTZ may have a relevant place in the treatment of high-risk or monotherapy-treated uncontrolled hypertensive patients requiring a more prompt, intensive, and sustained BP reduction, in line with the

  5. Combination Immunotherapy after ASCT for Multiple Myeloma Using MAGE-A3/Poly-ICLC Immunizations Followed by Adoptive Transfer of Vaccine-Primed and Costimulated Autologous T Cells

    PubMed Central

    Rapoport, Aaron P.; Aqui, Nicole A.; Stadtmauer, Edward A; Vogl, Dan T.; Xu, Yin Yan; Kalos, Michael; Cai, Ling; Fang, Hong-Bin; Weiss, Brendan M.; Badros, Ashraf; Yanovich, Saul; Akpek, Gorgun; Tsao, Patricia; Cross, Alan; Mann, Dean; Philip, Sunita; Kerr, Naseem; Brennan, Andrea; Zheng, Zhaohui; Ruehle, Kathleen; Milliron, Todd; Strome, Scott E.; Salazar, Andres M.; Levine, Bruce L.; June, Carl H.

    2015-01-01

    Purpose Myeloma-directed cellular immune responses after autologous stem cell transplantation (ASCT) may reduce relapse rates. We studied whether coinjecting the TLR-3 agonist and vaccine adjuvant Poly-ICLC with a MAGE-A3 peptide vaccine was safe and would elicit a high frequency of vaccine-directed immune responses when combined with vaccine-primed and costimulated autologous T cells. Experimental Design In a phase II clinical trial (NCT01245673), we evaluated the safety and activity of ex vivo expanded autologous T cells primed in vivo using a MAGE-A3 multipeptide vaccine (compound GL-0817) combined with Poly-ICLC (Hiltonol), granulocyte macrophage colony-stimulating factor (GM-CSF) ± montanide. Twenty-seven patients with active and/or high-risk myeloma received autografts followed by anti-CD3/anti-CD28–costimulated autologous T cells, accompanied by MAGE-A3 peptide immunizations before T-cell collection and five times after ASCT. Immune responses to the vaccine were evaluated by cytokine production (all patients), dextramer binding to CD8+ T cells, and ELISA performed serially after transplant. Results T-cell infusions were well tolerated, whereas vaccine injection site reactions occurred in >90% of patients. Two of nine patients who received montanide developed sterile abscesses; however, this did not occur in the 18 patients who did not receive montanide. Dextramer staining demonstrated MAGE-A3–specific CD8 T cells in 7 of 8 evaluable HLA-A2+ patients (88%), whereas vaccine-specific cytokine-producing T cells were generated in 19 of 25 patients (76%). Antibody responses developed in 7 of 9 patients (78%) who received montanide and only weakly in 2 of 18 patients (11%) who did not. The 2-year overall survival was 74% [95% confidence interval (CI), 54%–100%] and 2-year event-free survival was 56% (95% CI, 37%–85%). Conclusions A high frequency of vaccine-specific T-cell responses were generated after transplant by combining costimulated autologous T

  6. 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

    2015-01-09

    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.

  7. 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

  8. Sarcoidosis presenting with multiple tattoo granulomata

    PubMed Central

    Iveson, J. M. I.; Cotterill, J. A.; Wright, V.

    1975-01-01

    A patient with sarcoidosis, multiple tattoo granulomata and arthritis is described. A combination of tattoo granulomata unrelated to any one colour in the tattoo and granulomatous inflammation elsewhere is indicative of sarcoidosis. ImagesFig. 1Fig. 2 PMID:1197172

  9. 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.

  10. Multiple acousto-optic q-switch

    DOEpatents

    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.

  11. Multiple acousto-optic q-switch

    DOEpatents

    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.

  12. Combined linkage and linkage disequilibrium QTL mapping in multiple families of maize (Zea mays L.) line crosses highlights complementarities between models based on parental haplotype and single locus polymorphism.

    PubMed

    Bardol, N; Ventelon, M; Mangin, B; Jasson, S; Loywick, V; Couton, F; Derue, C; Blanchard, P; Charcosset, A; Moreau, Laurence

    2013-11-01

    Advancements in genotyping are rapidly decreasing marker costs and increasing marker density. This opens new possibilities for mapping quantitative trait loci (QTL), in particular by combining linkage disequilibrium information and linkage analysis (LDLA). In this study, we compared different approaches to detect QTL for four traits of agronomical importance in two large multi-parental datasets of maize (Zea mays L.) of 895 and 928 testcross progenies composed of 7 and 21 biparental families, respectively, and genotyped with 491 markers. We compared to traditional linkage-based methods two LDLA models relying on the dense genotyping of parental lines with 17,728 SNP: one based on a clustering approach of parental line segments into ancestral alleles and one based on single marker information. The two LDLA models generally identified more QTL (60 and 52 QTL in total) than classical linkage models (49 and 44 QTL in total). However, they performed inconsistently over datasets and traits suggesting that a compromise must be found between the reduction of allele number for increasing statistical power and the adequacy of the model to potentially complex allelic variation. For some QTL, the model exclusively based on linkage analysis, which assumed that each parental line carried a different QTL allele, was able to capture remaining variation not explained by LDLA models. These complementarities between models clearly suggest that the different QTL mapping approaches must be considered to capture the different levels of allelic variation at QTL involved in complex traits.

  13. 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.

  14. 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…

  15. 20 CFR 220.104 - Multiple impairments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Multiple impairments. 220.104 Section 220.104... DISABILITY Evaluation of Disability § 220.104 Multiple impairments. To determine whether the claimant's... impairments could be the basis of eligiblity under the law, the combined effect of all of the...

  16. 20 CFR 416.923 - Multiple impairments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Multiple impairments. 416.923 Section 416.923... DISABLED Determining Disability and Blindness Evaluation of Disability § 416.923 Multiple impairments. In... the combined effect of all of your impairments without regard to whether any such impairment,...

  17. Multiple roads lead to Rome: combined high-intensity aerobic and strength training vs. gross motor activities leads to equivalent improvement in executive functions in a cohort of healthy older adults.

    PubMed

    Berryman, Nicolas; Bherer, Louis; Nadeau, Sylvie; Lauzière, Séléna; Lehr, Lora; Bobeuf, Florian; Lussier, Maxime; Kergoat, Marie Jeanne; Vu, Thien Tuong Minh; Bosquet, Laurent

    2014-01-01

    cognition in healthy older adults. Such results call for further investigation of the multiple physiological pathways by which physical exercise can impact cognition in older adults.

  18. Multiple Sparse Representations Classification

    PubMed Central

    Plenge, Esben; Klein, Stefan S.; Niessen, Wiro J.; Meijering, Erik

    2015-01-01

    Sparse representations classification (SRC) is a powerful technique for pixelwise classification of images and it is increasingly being used for a wide variety of image analysis tasks. The method uses sparse representation and learned redundant dictionaries to classify image pixels. In this empirical study we propose to further leverage the redundancy of the learned dictionaries to achieve a more accurate classifier. In conventional SRC, each image pixel is associated with a small patch surrounding it. Using these patches, a dictionary is trained for each class in a supervised fashion. Commonly, redundant/overcomplete dictionaries are trained and image patches are sparsely represented by a linear combination of only a few of the dictionary elements. Given a set of trained dictionaries, a new patch is sparse coded using each of them, and subsequently assigned to the class whose dictionary yields the minimum residual energy. We propose a generalization of this scheme. The method, which we call multiple sparse representations classification (mSRC), is based on the observation that an overcomplete, class specific dictionary is capable of generating multiple accurate and independent estimates of a patch belonging to the class. So instead of finding a single sparse representation of a patch for each dictionary, we find multiple, and the corresponding residual energies provides an enhanced statistic which is used to improve classification. We demonstrate the efficacy of mSRC for three example applications: pixelwise classification of texture images, lumen segmentation in carotid artery magnetic resonance imaging (MRI), and bifurcation point detection in carotid artery MRI. We compare our method with conventional SRC, K-nearest neighbor, and support vector machine classifiers. The results show that mSRC outperforms SRC and the other reference methods. In addition, we present an extensive evaluation of the effect of the main mSRC parameters: patch size, dictionary size, and

  19. Management of multiple sclerosis.

    PubMed

    Perrin Ross, Amy

    2013-11-01

    Patients with multiple sclerosis (MS), a disease of the central nervous system that disrupts signals within the brain and also the signals between the brain and body, will likely experience symptoms that may negatively impact their quality of life (QOL). Due to the complexity of MS and its disease burden, multidisciplinary management that combines pharmacologic and nonpharmacologic strategies with patient education is necessary. Diagnosing relapses of MS in clinical practice can be difficult due to the multiple subtypes of MS, variations of symptomatology, and pseudo-relapses. Managing relapses also presents its own set of challenges, for example, evaluating if treatment is appropriate and determining which agent would be most effective for a patient if treatment is recommended. Patient education is essential for achieving optimal outcomes for patients with MS and improving patient QOL, and should increase awareness of: (1) the disease itself and its progression; (2) the signs and symptoms of MS; (3) current treatment strategies and plan of care; (4) the recognition and management of relapses; (5) the value of treatment adherence and impact of nonadherence; and (6) hope for the future. The management of active MS may be further complicated by the complex variety of pharmacotherapeutic options, and in some instances, by having to switch between agents and drug classes. Newer agents in development (eg, alemtuzumab, ocrelizumab, laquinimod) offer the opportunity to expand the therapeutic armamentarium, although further long-term data are required to evaluate any safety concerns associated with newer agents.

  20. 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

  1. Multiple Disabilities. NICHCY Disability Fact Sheet #10

    ERIC Educational Resources Information Center

    National Dissemination Center for Children with Disabilities, 2013

    2013-01-01

    The term "multiple disabilities" is general and broad. From the term, you cannot tell how many disabilities a child has; which disabilities are involved; or how severe each disability is. Many combinations of disabilities are possible. The different disabilities will also have a combined impact. That is why it is also important to ask:…

  2. Resistant multiple sparse canonical correlation.

    PubMed

    Coleman, Jacob; Replogle, Joseph; Chandler, Gabriel; Hardin, Johanna

    2016-04-01

    Canonical correlation analysis (CCA) is a multivariate technique that takes two datasets and forms the most highly correlated possible pairs of linear combinations between them. Each subsequent pair of linear combinations is orthogonal to the preceding pair, meaning that new information is gleaned from each pair. By looking at the magnitude of coefficient values, we can find out which variables can be grouped together, thus better understanding multiple interactions that are otherwise difficult to compute or grasp intuitively. CCA appears to have quite powerful applications to high-throughput data, as we can use it to discover, for example, relationships between gene expression and gene copy number variation. One of the biggest problems of CCA is that the number of variables (often upwards of 10,000) makes biological interpretation of linear combinations nearly impossible. To limit variable output, we have employed a method known as sparse canonical correlation analysis (SCCA), while adding estimation which is resistant to extreme observations or other types of deviant data. In this paper, we have demonstrated the success of resistant estimation in variable selection using SCCA. Additionally, we have used SCCA to find multiple canonical pairs for extended knowledge about the datasets at hand. Again, using resistant estimators provided more accurate estimates than standard estimators in the multiple canonical correlation setting. R code is available and documented at https://github.com/hardin47/rmscca.

  3. 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.

  4. 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…

  5. Combining Multiple Knowledge Sources for Continuous Speech Recognition

    DTIC Science & Technology

    1989-08-01

    another input. The dictionary is the lexical knowledge source, in which phonological rules of English are used to represent each lexical item in...grammatical constraints. Such models allow all word possibilities but with different piobabilities such that the urplexity of the grammar is substantially...lower than the size of the vocabulary. The recognition search process then uses the word phonetic models and the statistical grammar to find the most

  6. 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.

  7. 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.

  8. Multiple Myeloma: An Update

    PubMed Central

    Al-Farsi, Khalil

    2013-01-01

    Multiple myeloma is a rare, largely incurable malignant disease of plasma cells. Patients usually present with hypercalcemia, renal insufficiency, anemia and/or lytic bony lesions along with a monoclonal protein in the serum and/or urine in addition to an increase in the number of clonal plasma cells in the bone marrow. Patients with myeloma live on an average for five to seven years, with their survival dependent on the presence or absence of different prognostic markers. Treatment of younger fit patients is with induction therapy consisting of steroids with one or more novel anti-myeloma agents followed by high dose melphalan and autologous stem cell transplantation, while older and less fit patients are treated with melphalan-based combination chemotherapy. Supportive care is of paramount importance and includes the use of bisphosphonates, prophylactic antibiotics, thrombosis prophylaxis and the use of hematopoietic growth factors along with the treatment of complications of disease and its therapy. As more progress is being made and deeper responses are being attained, the disease might turn into a potentially curable one in the near future. PMID:23386937

  9. Multiple valence superatoms.

    PubMed

    Reveles, J U; Khanna, S N; Roach, P J; Castleman, A W

    2006-12-05

    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.

  10. Multiple Family Group Therapy: An Interpersonal/Postmodern Approach.

    ERIC Educational Resources Information Center

    Thorngren, Jill M.; Kleist, David M.

    2002-01-01

    Multiple Family Group Therapy has been identified as a viable treatment model for a variety of client populations. A combination of family systems theories and therapeutic group factors provide the opportunity to explore multiple levels of intrapersonal and interpersonal relationships between families. This article depicts a Multiple Family Group…

  11. Multiple sclerosis - discharge

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000129.htm Multiple sclerosis - discharge To use the sharing features on this ... Your doctor has told you that you have multiple sclerosis (MS). This disease affects the brain and spinal ...

  12. Challenges of Parenting Multiples

    MedlinePlus

    ... the American Society for Reproductive Medicine Challenges of Parenting Multiples There are many psychological, social, and economic ... the unique challenges and rewards that come from parenting multiples. For more information on the medical aspects ...

  13. Twins, Triplets, Multiple Births

    MedlinePlus

    ... deliver by C-section, especially if there are three babies or more. Parenting multiples can be a challenge. Volunteer help and support groups for parents of multiples can help. Dept. of Health and ...

  14. 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

  15. Multiple annular linear diffractive axicons.

    PubMed

    Bialic, Emilie; de la Tocnaye, Jean-Louis de Bougrenet

    2011-04-01

    We propose a chromatic analysis of multiple annular linear diffractive axicons. Large aperture axicons are optical devices providing achromatic nondiffracting beams, with an extended depth of focus, when illuminated by a white light source, due to chromatic foci superimposition. Annular apertures introduce chromatic foci separation, and because chromatic aberrations result in focal segment axial shifts, polychromatic imaging properties are partially lost. We investigate here various design parameters that can be used to achieve color splitting, filtering, and combining using these properties. In order to improve the low-power efficiency of a single annular axicon, we suggest a spatial multiplexing of concentric annular axicons with different sizes and periods we call multiple annular aperture diffractive axicons (MALDAs). These are chosen to maintain focal depths while enabling color imaging with sufficient diffraction efficiency. Illustrations are given for binary phase diffractive axicons, considering technical aspects such as grating design wavelength and phase dependence due to the grating thickness.

  16. 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.

  17. Birth control pills - combination

    MedlinePlus

    The pill - combination; Oral contraceptives - combination; OCP - combination; Contraception - combination; BCP - combination ... Birth control pills help keep you from getting pregnant. When taken daily, they are one of the most ...

  18. Rorschach indicators of Multiple Personality Disorder.

    PubMed

    Labott, S M; Leavitt, F; Braun, B G; Sachs, R G

    1992-08-01

    The increase in reported cases of Multiple Personality Disorder underscores a great need to differentiate clearly this from other psychiatric disorders and from simulation of Multiple Personality Disorder. Two sets of Rorschach signs have been advanced as clinical markers by their developers, namely Barach and also Wagner, Allison, and Wagner. As the Wagner signs are prevalent in much of the research on Rorschach responses in Multiple Personality Disorder, the purpose of the present study was to evaluate these signs using Wagner's administration and the resulting Rorschach protocols of 16 Multiple Personality Disorder patients and 16 psychiatric controls. Analysis indicated that this system was deficient in correctly classifying these 32 protocols. A new marker, the Splitting Response, emerged, however, which was more useful. This response, in combination with at least one Dissociative response, produced an accuracy rate of 94%. These new criteria may be useful aids in the detection of Multiple Personality Disorder from Rorschach protocols. Replication is urged.

  19. Oral ixazomib maintenance therapy in multiple myeloma.

    PubMed

    Offidani, Massimo; Corvatta, Laura; Gentili, Silvia; Maracci, Laura; Leoni, Pietro

    2016-01-01

    Continuous therapy has proven to be an effective therapeutic strategy to improve the outcome of both young and elderly multiple myeloma patients. Remarkably, lenalidomide and bortezomib showed to play a crucial role in this setting due to their safety profile allowing long-term exposure. Ixazomib, the first oral proteasome inhibitor to be evaluated in multiple myeloma, exerts substantial anti-myeloma activity as a single agent and particularly in combination with immunomodulatory drugs and it may be an attractive option for maintenance therapy. Here we address the issue of maintenance therapy as part of a therapeutic approach of multiple myeloma patients focusing on the potential role of ixazomib.

  20. Auditory Spatial Receptive Fields Created by Multiplication

    NASA Astrophysics Data System (ADS)

    Peña, José Luis; Konishi, Masakazu

    2001-04-01

    Examples of multiplication by neurons or neural circuits are scarce, although many computational models use this basic operation. The owl's auditory system computes interaural time (ITD) and level (ILD) differences to create a two-dimensional map of auditory space. Space-specific neurons are selective for combinations of ITD and ILD, which define, respectively, the horizontal and vertical dimensions of their receptive fields. A multiplication of separate postsynaptic potentials tuned to ITD and ILD, rather than an addition, can account for the subthreshold responses of these neurons to ITD-ILD pairs. Other nonlinear processes improve the spatial tuning of the spike output and reduce the fit to the multiplicative model.

  1. Multiple Myeloma: Diagnosis and Treatment

    PubMed Central

    Rajkumar, S. Vincent; Kumar, Shaji

    2016-01-01

    The diagnosis and treatment of multiple myeloma (MM) has changed dramatically in the last decade. The disease definition has been updated to allow highly specific biomarkers in addition to established markers of end-organ damage. The staging system has been revised to combine both measures of tumor burden and disease biology. Advances in therapy have resulted in a significant improvement of overall survival. New drugs introduced in the last few years include carfilzomib, pomalidomide, and panobinostat. In addition, monoclonal antibodies such as elotuzumab and daratumumab have shown promising clinical activity. In this review, we outline the current approach to diagnosis, prognosis, and management of MM. PMID:26763514

  2. Spasticity management in multiple sclerosis.

    PubMed

    Hughes, Christina; Howard, Ileana M

    2013-11-01

    Spasticity is a prevalent and potentially disabling symptom common in individuals with multiple sclerosis. Adequate evaluation and management of spasticity requires a careful assessment of the patient's history to determine functional impact of spasticity and potential exacerbating factors, and physical examination to determine the extent of the condition and culpable muscles. A host of options for spasticity management are available: therapeutic exercise, physical modalities, complementary/alternative medicine interventions, oral medications, chemodenervation, and implantation of an intrathecal baclofen pump. Choice of treatment hinges on a combination of the extent of symptoms, patient preference, and availability of services.

  3. Creating Multiple Processes from Multiple Intelligences.

    ERIC Educational Resources Information Center

    Wolffe, Robert; Robinson, Helja; Grant, Jean Marie

    1998-01-01

    Howard Gardner's multiple-intelligences theory stresses that all humans possess the various intelligences (linguistic, logical-mathematical, spatial, bodily-kinesthetic, musical, interpersonal, intrapersonal, and naturalist) to differing degrees, and most people can attain adequate competency levels. This article provides a sample checklist for…

  4. On Multiple Questions and Multiple WH Fronting.

    ERIC Educational Resources Information Center

    Rudin, Catherine

    An analysis of languages with multiple fronting of WH words (who, what, whom, etc.) looks in detail at Polish, Serbo-Croatian, Czech, Bulgarian (Slavic languages), and Romanian (a Romance language). In spite of their superficial similarity, the Slavic and East European languages that normally put all WH words at the beginning of clauses fall into…

  5. Complications of multiple myeloma.

    PubMed

    Bladé, Joan; Rosiñol, Laura

    2007-12-01

    Multiple myeloma, also known as myeloma or plasma cell myeloma, is a progressive hematologic disease. Complications of multiple myeloma include renal insufficiency, hematologic complications (anemia, bone marrow failure, bleeding disorders), infections, bone complications (pathologic fractures, spinal cord compression, hyercalcemia), and neurologic complications (spinal cord and nerve root compression, intracranial plasmacytomas, leptomeningeal involvement, among others). This article reviews these various complications connected to multiple myeloma, examining their various causes and possible treatment.

  6. Multiple Instance Fuzzy Inference

    DTIC Science & Technology

    2015-12-02

    INFERENCE A novel fuzzy learning framework that employs fuzzy inference to solve the problem of multiple instance learning (MIL) is presented. The...fuzzy learning framework that employs fuzzy inference to solve the problem of multiple instance learning (MIL) is presented. The framework introduces a...or learned from data. In multiple instance problems, the training data is ambiguously labeled. Instances are grouped into bags, labels of bags are

  7. Multiple-illumination photoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Barber, Quinn M.; Zemp, Roger J.

    2016-03-01

    Previously we described the potential for multiple illumination photoacoustic tomography to provide quantitative reconstructions, however this work used only simulated data. We have developed a custom photoacoustic-ultrasound tomography system capable of multiple illuminations and parallel acquisition from a 256 element 5 MHz transducer ring array with 8-cm diameter. The multiple illumination scheme uses a free-space light delivery geometry where a rotational stage scans a pulsed laser beam onto different incident locations around the sample. For each illumination location a photoacoustic image is reconstructed using a modified backprojection algorithm. Images from different source locations have the potential to be combined to form an improved deep-tissue image using our previously developed iterative algorithms. We complement the photoacoustic imaging data with unique ultrasound imaging data. Most previous ultrasound tomography methods have used migration algorithms, iterative ray-based analysis, wave-equation modeling, or frequency-based algorithms that all demand large amounts of data and computational power. We propose a new UST method that offers isotropic resolution, provides scattering contrast, as well as the potential for measuring ultrasound scattering anisotropy and decoupling density and compressibility contributions. The imaging system is driven by a Verasonics scan engine and programmed for both ultrasound and photoacoustic imaging modes. Resolution has been measured to be 150 μm for ultrasound and 200 μm for photoacoustic images. Imaging capabilities are demonstrated on phantoms with custom-tailored ultrasound scattering and optical properties, as well as in murine models.

  8. [Multiple sclerosis: current immunological aspects].

    PubMed

    Cuevas-García, Carlos

    2017-01-01

    Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration. In this review, the immune reaction main components and neurodegeneration present in multiple sclerosis are analyzed, as well as the inflammatory cascade associated with demyelination. Available treatments' main purpose is to modulate aspects related to the adaptive immune response (B and T cells). The therapeutic challenge will be antigen-specific immune-tolerance induction, for example, with the use of tolerance protocols with peptides or DNA or nanoparticles vaccines. Future therapies should aim to control innate components (microglia, macrophages, astrocytes) and to promote remyelination. To optimize the treatment, a combined therapeutic approach targeting the control of inflammatory and neurodegenerative components of the disease and monitoring of biomarkers will be necessary.

  9. Optical multiple object tracking techniques

    NASA Astrophysics Data System (ADS)

    Liu, Hua-Kuang; Chao, Tien-Hsin

    1989-02-01

    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.

  10. 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.

  11. 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.

  12. Lethal multiple pterygium syndrome

    PubMed Central

    Joshi, Tulika; Noor, Nazia Nagori; Kural, Moolraj; Tripathi, Amita

    2016-01-01

    The multiple pterygium syndrome is consist of wide range of fetal malformations which have a genetic linkage. A defect in embryonic acetylcholine receptor which can be inherited as autosomal recessive, autosomal dominant, or X-linked fashion is the cause of this syndrome. We present a sporadic case of lethal multiple pterygium syndrome. PMID:27843868

  13. Multiple Frequency Parametric Sonar

    DTIC Science & Technology

    2015-09-28

    300003 1 MULTIPLE FREQUENCY PARAMETRIC SONAR STATEMENT OF GOVERNMENT INTEREST [0001] The invention described herein may be manufactured and...beams. However, the multiple nonlinear interactions are not taken advantage of in order to generate additional efficiencies, bandwidth, and SNR...array. [0050] It will be understood that many additional changes in details, materials , steps, and arrangements of parts which have been described

  14. 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.

  15. Assessing Children's Multiplicative Thinking

    ERIC Educational Resources Information Center

    Hurst, Chris; Hurrell, Derek

    2016-01-01

    Multiplicative thinking is a "big idea" of mathematics that underpins much of the mathematics learned beyond the early primary school years. This paper reports on a current study that utilises an interview tool and a written quiz to gather data about children's multiplicative thinking. The development of the tools and some of the…

  16. 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.

  17. 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…

  18. 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…

  19. 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…

  20. Multiple scattering technique lidar

    NASA Technical Reports Server (NTRS)

    Bissonnette, Luc R.

    1992-01-01

    The Bernouilli-Ricatti equation is based on the single scattering description of the lidar backscatter return. In practice, especially in low visibility conditions, the effects of multiple scattering can be significant. Instead of considering these multiple scattering effects as a nuisance, we propose here to use them to help resolve the problems of having to assume a backscatter-to-extinction relation and specifying a boundary value for a position far remote from the lidar station. To this end, we have built a four-field-of-view lidar receiver to measure the multiple scattering contributions. The system has been described in a number of publications that also discuss preliminary results illustrating the multiple scattering effects for various environmental conditions. Reported here are recent advances made in the development of a method of inverting the multiple scattering data for the determination of the aerosol scattering coefficient.

  1. 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…

  2. Categorical Variables in Multiple Regression: Some Cautions.

    ERIC Educational Resources Information Center

    O'Grady, Kevin E.; Medoff, Deborah R.

    1988-01-01

    Limitations of dummy coding and nonsense coding as methods of coding categorical variables for use as predictors in multiple regression analysis are discussed. The combination of these approaches often yields estimates and tests of significance that are not intended by researchers for inclusion in their models. (SLD)

  3. 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.

  4. Multiple Personality Disorder: Concepts and Cases.

    ERIC Educational Resources Information Center

    Lindsley, Hope L.

    1992-01-01

    Presents two case examples illustrating nature and etiology of multiple personality disorder in two clients and describing their entry into counseling and progress through treatment. Compares and contrasts cases in areas of diagnosis, symptoms, history, and treatment. Suggests that mental health counselors combine firmness with flexibility in…

  5. Panobinostat for the Treatment of Multiple Myeloma.

    PubMed

    Laubach, Jacob P; Moreau, Philippe; San-Miguel, Jesús F; Richardson, Paul G

    2015-11-01

    Panobinostat is a potent oral deacetylase inhibitor that alters gene expression through epigenetic mechanisms and inhibits protein degradation. It was recently approved by the FDA and EMA for use in combination with bortezomib and dexamethasone in patients with multiple myeloma who have received ≥2 prior regimens, including bortezomib and an immunomodulatory drug. Panobinostat was approved based on results from the phase III PANORAMA 1 trial in patients with relapsed or relapsed and refractory multiple myeloma, which showed that panobinostat plus bortezomib and dexamethasone significantly extended progression-free survival (median, 12.0 months) compared with placebo plus bortezomib and dexamethasone (median, 8.1 months; P < 0.0001). Additional ongoing trials are evaluating panobinostat in combination with other partners in the relapsed/refractory and newly diagnosed treatment settings. This review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma.

  6. Percutaneous Intraductal Radiofrequency Ablation Combined with Biliary Stent Placement for Nonresectable Malignant Biliary Obstruction Improves Stent Patency but not Survival

    PubMed Central

    Wang, Jianfeng; Zhao, Lizhen; Zhou, Chuanguo; Gao, Kun; Huang, Qiang; Wei, Baojie; Gao, Jun

    2016-01-01

    Abstract Although radiofrequency (RF) ablation has been accepted as a curative treatment modality for solid organ tumors, intraductal RF ablation for malignant biliary obstruction has not been widely described. The aim of this study was to evaluate the feasibility, safety, and effi