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Sample records for combined multiple intraluminal

  1. Inter- and intraobserver agreement in 24-hour combined multiple intraluminal impedance and pH measurement in children.

    PubMed

    Pilic, Denisa; Höfs, Carolin; Weitmann, Sandra; Nöh, Frank; Fröhlich, Thorsten; Skopnik, Heino; Köhler, Henrik; Wenzl, Tobias G; Schmidt-Choudhury, Anjona

    2011-09-01

    Assessment of intra- and interobserver agreement in multiple intraluminal impedance (MII) measurement between investigators from different institutions. Twenty-four 18- to 24-hour MII tracings were randomly chosen from 4 different institutions (6 per center). Software-aided automatic analysis was performed. Each result was validated by 2 independent investigators from the 4 different centers (4 investigator combinations). For intraobserver agreement, 6 measurements were analyzed twice by the same investigator. Agreement between investigators was calculated using the Cohen kappa coefficient. Interobserver agreement: 13 measurements showed a perfect agreement (kappa > 0.8); 9 had a substantial (kappa 0.61-0.8), 1 a moderate (kappa coefficient 0.41 to 0.6), and 1 a fair agreement (kappa coefficient 0.11-0.4). Median kappa value was 0.83. Intraobserver agreement: 5 tracings showed perfect and 1 showed a substantial agreement. The median kappa value was 0.88. Most measurements showed substantial to perfect intra- and interobserver agreement. Still, we found a few outliers presumably caused by poorer signal quality in some tracings rather than being observer dependent. An improvement of analysis results may be achieved by using a standard analysis protocol, a standardized method for judging tracing quality, better training options for method users, and more interaction between investigators from different institutions.

  2. Clinical report on external irradiation combined with californium-252 neutron intraluminal brachytherapy for cervical carcinoma treatment.

    PubMed

    Zhao, Huanyu; Wang, Keming; Sun, Jian; Geng, Xin; Zhang, Weiming

    2007-01-01

    Neutron rays produce high linear energy transfer radiation, which has particular radiobiological characteristics. The aim of the study was to observe the curative effects and complications of external irradiation combined with californium-252 (252Cf) neutron intraluminal brachytherapy for treatment of cervical carcinoma. From December 2000 to December 2004, 128 cases of cervical carcinoma staged IIA to IIIB were treated with 252Cf neutron intraluminal brachytherapy using 8-10 Gy-eq per fraction, once a week. The total dose at reference point A was 36-40 Gy-eq in 4 to 5 fractions. From the second day after 252Cf neutron intraluminal brachytherapy, the whole pelvic cavity was treated with 6 MV X-ray external irradiation, applying 2 Gy per fraction 4 times per week. After 20-24 Gy of external irradiation, the center of the whole pelvic field was blocked with a 4-cm-wide lead shield; the total dose of external irradiation was 44-50 Gy. The short-term curative effects were 95.3% complete remissions and 4.7% partial remissions. The 3-year and 5-year local control rates were 93.5% and 87.9%, respectively. The 3-year and 5-year survival rates were 87.5% and 70%, respectively. The rates of radiation complications were 4.7% for radiation cystitis, 7.8% for radiation proctitis, 6.3% for vaginal contracture and adhesion, and 5.5% for protracted radiation proctitis. The results of univariate and multivariate analysis indicated that differentiation of tumor cells and lymphatic metastasis are the main factors related to the clinical prognosis of cervical carcinoma. A combination of external irradiation with 252Cf neutron intraluminal brachytherapy for treatment of cervical carcinoma can be well tolerated by patients. The rate of local tumor control is high and radiation complications are few.

  3. Impact of total fundoplication on esophageal transit: analysis by combined multichannel intraluminal impedance and manometry.

    PubMed

    Del Genio, Gianmattia; Tolone, Salvatore; Del Genio, Federica; D'Alessandro, Antonio; Brusciano, Luigi; Aggarwal, Rajesh; Conzo, Giovanni; Orditura, Michele; Docimo, Ludovico; Del Genio, Alberto

    2012-01-01

    Laparoscopic total fundoplication is considered the most effective surgical option for gastroesophageal reflux (GER) disease. Some authors assume that total fundoplication may expose the patient to delayed transit of the swallowed bolus and increased risk of dysphagia, particularly when peristaltic dysfunction is present. We undertook this study to evaluate by means of combined multichannel intraluminal impedance and esophageal manometry (MII-EM) the impact of fundoplication on esophageal physiology. An objective measurement of the influence of the total wrap on bolus transit may be helpful in refining the optimal antireflux wrap (ie, partial vs. total). In this study, 25 consecutive patients who underwent laparoscopic Nissen-Rossetti fundoplication had MII-EM and combined 24-hour pH and multichannel intraluminal impedance (MII-pH) before and after the surgical procedure. All patients completed preoperative and postoperative symptom questionnaires. The following were calculated for liquid and viscous deglutition lower esophageal sphincter pressure and relaxation, distal esophageal amplitude, the number of complete esophageal bolus transits and the mean total bolus transit time. The acid and nonacid GER episodes were calculated by MII-pH with the patient in both upright and recumbent positions. The postoperative MII-EM showed an increased lower esophageal sphincter pressure (P < 0.05), whereas lower esophageal sphincter relaxation and distal esophageal amplitude did not change after surgery (P = NS). Complete esophageal bolus transits and bolus transit time did not change for liquid swallows (P = NS), but was more rapid for viscous after surgery (P < 0.05). Twenty-four hour pH monitoring confirmed the postoperative reduction of both acid and nonacid reflux (P < 0.05). Laparoscopic Nissen-Rossetti is effective in controlling both acid and nonacid GER without impairment of esophageal function. Appropriate preoperative investigation, meticulous patient selection and

  4. 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

  5. Tailored therapy for the refractory GERD patients by combined multichannel intraluminal impedance-pH monitoring.

    PubMed

    Xiao, Yinglian; Liang, Mengya; Peng, Sui; Zhang, Ning; Chen, Minhu

    2016-02-01

    About 30% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI). The reason for the PPI failure in Asian GERD patients has rarely been studied, and the therapy remained unclear. The aims were to explore the possible reasons for PPI failure and to treat these patients with the guidance of 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring. Thirty-nine consecutive patients with refractory GERD were enrolled; 24-h MII-pH monitoring was performed on PPI. The refractory GERD patients were grouped into acid overexposure, non-acid reflux, and functional heartburn after the MII-pH monitoring. Double dose of either PPI or paroxetine was administered to refractory GERD patients within different groups. The number of patients in groups of acid overexposure, non-acid reflux, and functional heartburn was 6, 12, and 21, respectively. The acid overexposure group had the most acid reflux events. Among the acid overexposure group, five (5/6) patients accomplish symptom relief with double dose of esomeprazole. For the patients in non-acid reflux group, double dose of esomeprazole made half (6/12) of the patients obtain symptom relief. For the patients in functional heartburn group, the paroxetine had relieved the symptoms in 14 patients among all the 21 patients. In total, with the guidance of MII-pH monitoring, 64.1% (25/39) of refractory GERD patients accomplished symptom relief. Acid overexposure, non-acid reflux, and functional heartburn were the common reasons for persistent reflux symptoms despite PPI. With the guidance of MII-pH, a tailored therapy could resolve the persistent reflux symptoms among two-third of patients. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  6. Combined esophageal intraluminal impedance, pH and skin conductance monitoring to detect discomfort in GERD infants.

    PubMed

    Cresi, Francesco; Castagno, Emanuele; Storm, Hanne; Silvestro, Leandra; Miniero, Roberto; Savino, Francesco

    2012-01-01

    The clinical significance of weakly acidic reflux in infants is unclear. Skin conductance is a novel not-invasive method to evaluate discomfort. The aim of our study was to evaluate reflux-induced discomfort in infants with gastroesophageal reflux disease using simultaneously combined skin conductance and esophageal multichannel intraluminal impedance and pH monitoring. Infants with gastroesophageal reflux symptoms were investigated for almost 20 hours divided into 120-second intervals. Temporal relationships between refluxes and discomfort were evaluated calculating the symptom association probability. Twelve infants aged 17-45 days were studied. Out of 194.38 hours of adequate artifact-free MII/pH and skin conductance monitoring, 584 reflux events were observed; 35.78% were positive for stress, of which 16.27% were acid and 83.73% weakly acidic. A significant association between refluxes and discomfort (p<0.05) was present in all infants. The intervals with reflux events showed increased skin conductance values compared to reflux-free intervals (p<0.001); SC values were similar for acid and weakly acidic reflux events. CONCLUSION/SIGNFICANCE: Discomfort was significantly associated with reflux events and did not differ between weakly acidic and acid refluxes. Our results may raise concerns about the over-prescription use of antacid drugs in the management of gastroesophageal reflux symptoms in infancy.

  7. 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.

  8. Combined esophageal multichannel intraluminal impedance and pH monitoring (MII -pH) in the diagnostics and treatment of gastroesophageal reflux disease and its complications.

    PubMed

    Masiak, Wioletta; Wallner, Grzegorz; Wallner, Jan; Pedowski, Tomasz; Solecki, Michał

    2011-09-01

    The technique of 24-hour esophageal multichannel intraluminal impedance monitoring combined with pH-metry (MII-pH) is currently considered to be the golden standard in the diagnostics of gastroesophageal reflux disease (GERD). The technique allows for differentiation of gas and liquid reflux as well as detection of non-acid reflux, which cannot be detected with other techniques that are based only on measuring the pH of gastric contents.THE AIM OF THE STUDY was to assess the usefulness of MII-pH in the diagnostics and treatment of GERD and its complications. MATERIAL AND METHODS. A group of 213 patients referred to II Katedra i Klinika Chirurgii Ogólnej, Gastroenterologicznej i Nowotworów Układu Pokarmowego Uniwersytetu Medycznego w Lublinie [the Second Faculty and Clinic of General and Gastrointestinal Surgery and Gastrointestinal Oncology at Medical University of Lublin] due to persistent symptoms of GERD and 21 volunteers without any clinical evidence of GERD underwent esophageal monitoring via MII-pH. The results were correlated with those of upper gastrointestinal tract endoscopy. The data gathered during MII-pH and endoscopy as well as information from questionnaires were entered into an MS Excel spreadsheet and subsequently analyzed with STATISTICA PL software. RESULTS AND CONCLUSIONS. MII-pH proved to be considerably more useful than conventional pHmetry in recording acid reflux. The sensitivity of pH-metry based on the MII-pH technique was established at 74%. GERD-induced changes in the esophageal mucosa result in decreased impedance baseline. The presence and severity of inflammatory esophageal lesions was proven to be associated with acid reflux episodes and proximal reflux episodes. No direct relationship between the grade of GERD and the occurrence of non-acid reflux episodes was confirmed. Non-acid reflux episodes were shown to predispose to non-erosive reflux disease (NERD). The results of this study confirm that MIIpH is an essential technique in

  9. COMBINED 24-HOURS ESOPHAGEAL PH MONITORING AND MULTICHANNEL INTRALUMINAL IMPEDANCE FOR COMPARISON OF GASTROESOPHAGEAL REFLUX IN CHILDREN WITH TYPICAL VERSUS ATYPICAL SYMPTOMS OF GASTROESOPHAGEAL REFLUX DISEASE.

    PubMed

    Dehghani, Seyed Mohsen; Taghavi, Seyed Alireza; Javaherizadeh, Hazhir; Nasri, Maryam

    2016-01-01

    - Gastroesophageal reflux disease is the most common esophageal disorder in pediatrics. - The aim of this study was to compare reflux parameters of typical and atypical symptoms of gastroesophageal reflux disease using 24-hour esophageal pH monitoring and multichannel intraluminal impedance in pediatric population. - In this prospective study, 43 patients aged less than 18 year with suspected gastroesophageal reflux disease were enrolled. The patients were divided into two groups based on the main presenting symptoms (typical versus atypical). Twenty four-hour pH monitoring and multichannel intraluminal impedance were performed in all the patients for comparing these two group regarding association of symptoms and reflux. Number of refluxes, pH related reflux, total reflux time, reflux more than 5 minutes, longest time of the reflux, lowest pH at reflux, reflux index were recorded and compared. Data comparison was done using SPSS. - The mean age of the patients was 5.7±3.4 years and 65.1% were male. Out of 43 patients 24 cases had typical symptoms and 19 had atypical symptoms. The mean reflux events detected by multichannel intraluminal impedance was more than mean reflux events detected by pH monitoring (308.4±115.8 vs 69.7±66.6) with P value of 0.037, which is statistically significant. The mean symptom index and symptom association probability were 35.01% ± 20.78% and 86.42% ± 25.79%, respectively in multichannel intraluminal impedance versus 12.73% ± 12.48% and 45.16% ± 42.29% in pH monitoring (P value <0.001). Number of acid reflux was 46.26±47.16 and 30.9±22.09 for atypical and typical symptoms respectively. The mean symptom index was 18.12% ± 13.101% and 8.30% ± 10.301% in atypical and typical symptoms respectively (P=0.034). Bolus clearance was longer in atypical symptoms compared typical symptoms(P<0.05). - Symptom index was significantly higher in atypical symptoms compared to typical symptoms. Higher number of acid reflux was found in children

  10. 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

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

    PubMed Central

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

    2014-01-01

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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Bortezomib Combination Therapy in Multiple Myeloma

    PubMed Central

    Kapoor, Prashant; Ramakrishnan, Vijay; Rajkumar, S. Vincent

    2012-01-01

    Bortezomib was approved for the treatment of multiple myeloma in 2003. Since then several bortezomib-based combination therapies have emerged. Although some combinations have been preceded by preclinical investigations, most have followed the inevitable process in which active (or potentially active) drugs are combined with each other to create new treatment regimens. Regimens that have combined bortezomib with corticosteroids, alkylating agents, thalidomide, and/or lenalidomide have resulted in high response rates. Despite the higher and often deeper response rates and prolongation of progression-free survival with bortezomib-based multiagent regimens, an overall survival (OS) advantage has not been demonstrated with most combinations compared to the sequential approach of utilizing anti-myeloma agents, particularly in patients less than 65 with newly diagnosed myeloma. The unique properties of some of these regimens can be taken into account when choosing a particular regimen based on the clinical scenario. For example, bortezomib, thalidomide, dexamethasone (VTD) has particular value in renal failure since none of the drugs need dose modification. Similarly, the combination chemotherapy regimen VDT-PACE (bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide) is of particular value in patients presenting with aggressive disease such as extramedullary plasmacytomas or plasma cell leukemia. Ongoing clinical trials are testing combinations of bortezomib with several other classes of agents, including monoclonal antibodies, and inhibitors of deacetylases, heat shock proteins, phosphatidyl inositol 3-kinase/Akt/mammalian target of rapamycin pathway and farnesyl transferase. PMID:22726546

  18. Intraluminal negative pressure wound therapy for optimizing pharyngeal reconstruction.

    PubMed

    Asher, Scott A; White, Hilliary N; Illing, Elisa A; Carroll, William R; Magnuson, J Scott; Rosenthal, Eben L

    2014-02-01

    Pharyngocutaneous fistula formation after pharyngeal reconstruction is one of the most common and challenging problems to manage. Despite many advances in management, the published success rates indicate a role for any adjuvant therapy that could potentially decrease this complication. To describe the use of intraluminal negative pressure dressings (NPDs) in pharyngeal reconstruction. Retrospective case series at a tertiary care academic hospital. Twelve laryngectomy patients underwent pharyngeal reconstruction augmented by placement of an intrapharyngeal NPD in combination with the introduction of vascularized tissue from August 2011 to May 2012. All patients had potential risk factors for compromised wound healing defined as previous radiation therapy, hypothyroidism, diabetes mellitus, compromised nutrition, or established pharyngocutaneous fistula. An NPD was placed in an intraluminal position spanning the length of the pharyngeal defect as part of the reconstructive procedure. The negative pressure sponge was attached to a standard nasogastric tube to which negative pressure was applied. External closure of the pharynx was then achieved with regional or free tissue transfer. Pharyngeal closure rates, timing until return to oral diet, identification of wound healing risk factors, and adverse events related to use of the device. Eleven of 12 patients (92%) achieved pharyngeal closure with reconstruction using negative pressure wound therapy. All patients had at least 1 potential risk factor for compromised wound healing, with 11 of 12 (92%) having 2 or more. Seven patients had an established pharyngocutaneous fistula, and 5 patients underwent primary reconstruction after laryngopharyngectomy. In 6 of these 7 patients undergoing fistula repair, pharyngeal closure was achieved, and they resumed an oral diet at 1 week postoperatively. The other had successful leak repair initially, but 1 week later developed a separate area of wound breakdown and a second fistula

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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.

  5. Combining multiple decisions: applications to bioinformatics

    NASA Astrophysics Data System (ADS)

    Yukinawa, N.; Takenouchi, T.; Oba, S.; Ishii, S.

    2008-01-01

    Multi-class classification is one of the fundamental tasks in bioinformatics and typically arises in cancer diagnosis studies by gene expression profiling. This article reviews two recent approaches to multi-class classification by combining multiple binary classifiers, which are formulated based on a unified framework of error-correcting output coding (ECOC). The first approach is to construct a multi-class classifier in which each binary classifier to be aggregated has a weight value to be optimally tuned based on the observed data. In the second approach, misclassification of each binary classifier is formulated as a bit inversion error with a probabilistic model by making an analogy to the context of information transmission theory. Experimental studies using various real-world datasets including cancer classification problems reveal that both of the new methods are superior or comparable to other multi-class classification methods.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Sequential or combination therapy for multiple myeloma.

    PubMed

    Nooka, Ajay; Lonial, Sagar

    2012-10-01

    In myeloma management, whether to offer sequential or combination therapies has largely remained elusive, partly for the reason that there are no conclusive studies evaluating this question and partly owing to the paradigm shift in myeloma outcomes over the last decade raising the same question again, but now in a different context with active agents such as immunomodulatory drugs and proteasome inhibitors being available. Historically, in myeloma, combination cytotoxic chemotherapy compared with the standard-of-care melphalan and prednisone regimen resulted in similar response rates, raising the question of efficacy of the cytotoxic combination therapies with high toxicities and the preference for sequential therapies in order to lower the toxicity of the chosen treatment. However, with the use of more active novel agents with favorable toxicity profiles such as bortezomib, thalidomide and lenalidomide, re-evaluation of this question is necessary.

  11. Under Pressure: Intraluminal Filling Pressures of Postpartum Hemorrhage Tamponade Balloons

    PubMed Central

    Antony, Kathleen M.; Racusin, Diana A.; Belfort, Michael A.; Dildy, Gary A.

    2017-01-01

    Objective Uterine tamponade by fluid-filled balloons is now an accepted method of controlling postpartum hemorrhage. Available tamponade balloons vary in design and material, which affects the filling attributes and volume at which they rupture. We aimed to characterize the filling capacity and pressure-volume relationship of various tamponade balloons. Study Design Balloons were filled with water ex vivo. Intraluminal pressure was measured incrementally (every 10 mL for the Foley balloons and every 50 mL for all other balloons). Balloons were filled until they ruptured or until 5,000 mL was reached. Results The Foley balloons had higher intraluminal pressures than the larger-volume balloons. The intraluminal pressure of the Sengstaken-Blakemore tube (gastric balloon) was initially high, but it decreased until shortly before rupture occurred. The Bakri intraluminal pressure steadily increased until rupture occurred at 2,850 mL. The condom catheter, BT-Cath, and ebb all had low intraluminal pressures. Both the BT-Cath and the ebb remained unruptured at 5,000 mL. Conclusion In the setting of acute hemorrhage, expeditious management is critical. Balloons that have a low intraluminal pressure-volume ratio may fill more rapidly, more easily, and to greater volumes. We found that the BT-Cath, the ebb, and the condom catheter all had low intraluminal pressures throughout filling. PMID:28497006

  12. Under Pressure: Intraluminal Filling Pressures of Postpartum Hemorrhage Tamponade Balloons.

    PubMed

    Antony, Kathleen M; Racusin, Diana A; Belfort, Michael A; Dildy, Gary A

    2017-04-01

    Objective Uterine tamponade by fluid-filled balloons is now an accepted method of controlling postpartum hemorrhage. Available tamponade balloons vary in design and material, which affects the filling attributes and volume at which they rupture. We aimed to characterize the filling capacity and pressure-volume relationship of various tamponade balloons. Study Design Balloons were filled with water ex vivo. Intraluminal pressure was measured incrementally (every 10 mL for the Foley balloons and every 50 mL for all other balloons). Balloons were filled until they ruptured or until 5,000 mL was reached. Results The Foley balloons had higher intraluminal pressures than the larger-volume balloons. The intraluminal pressure of the Sengstaken-Blakemore tube (gastric balloon) was initially high, but it decreased until shortly before rupture occurred. The Bakri intraluminal pressure steadily increased until rupture occurred at 2,850 mL. The condom catheter, BT-Cath, and ebb all had low intraluminal pressures. Both the BT-Cath and the ebb remained unruptured at 5,000 mL. Conclusion In the setting of acute hemorrhage, expeditious management is critical. Balloons that have a low intraluminal pressure-volume ratio may fill more rapidly, more easily, and to greater volumes. We found that the BT-Cath, the ebb, and the condom catheter all had low intraluminal pressures throughout filling.

  13. 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

  14. [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.

  15. Theoretical comparison of intraluminal heating techniques.

    PubMed

    Kok, H P; van Haaren, P M A; van de Kamer, J B; Crezee, J

    2007-06-01

    This study compared simulated temperature distributions of intraluminal heating devices, concerning penetration and homogeneity. A hot water balloon, a 434-MHz monopole and a 915-MHz dipole antenna, both with incorporated cooling, and a 27-MHz applicator were investigated. The hot water balloon had an inlet temperature of 45 degrees C and a flow rate of 7.85 ml s(-1). The cooling water and air had a temperature of 41 degrees C and 37 degrees C and a flow rate of 5.89 ml s(-1) and 1.8 l s(-1), respectively. A 27-MHz applicator consisting of one or two electrode(s) was modelled to demonstrate axial steering for inhomogeneous tissue properties. Calculated power distributions were scaled to a total power of 10 W in tissue before the corresponding temperature distributions were calculated. The hot water balloon and the 27-MHz device showed a thermal penetration depth of approximately 4 and approximately 10 mm, respectively. The penetration depths of the 434- and 915-MHz applicators were comparable: approximately 10 and approximately 16 mm with water and air cooling, respectively. With the 27-MHz applicator, spatial steering was applied to minimize temperature gradients along the applicator. The 434- and 915-MHz antennas have no steering possibilities. The temperature distribution of the hot water balloon is not affected by inhomogeneous dielectric properties, only slightly by inhomogeneous perfusion. A hot water balloon is useful for heating tumours with a limited infiltration in tissue, while a 27-MHz device has the best potential to realize a homogeneous temperature distribution in larger tumours.

  16. 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.

  17. 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.

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Randomized study combining interferon and glatiramer acetate in multiple sclerosis.

    PubMed

    Lublin, Fred D; Cofield, Stacey S; Cutter, Gary R; Conwit, Robin; Narayana, Ponnada A; Nelson, Flavia; Salter, Amber R; Gustafson, Tarah; Wolinsky, Jerry S

    2013-03-01

    A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30 μg intramuscularly weekly and glatiramer acetate (GA) 20 mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis. A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. Combination IFN+GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences. Copyright © 2013 American Neurological Association.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. Emerging drugs and combinations to treat multiple myeloma

    PubMed Central

    Larocca, Alessandra; Mina, Roberto; Gay, Francesca; Bringhen, Sara; Boccadoro, Mario

    2017-01-01

    In the past few years, multiple targeted therapies and immunotherapies including second generation immunomodulatory drugs (pomalidomide) and proteasome inhibitors (carfilzomib, ixazomib), monoclonal antibodies and checkpoint inhibitors were approved for the treatment of myeloma or entered advanced phases of clinical testing. These agents showed significant activity in advanced myeloma and increased the available treatment strategies. Pomalidomide is well-tolerated and effective in patients with relapsed/refractory multiple myeloma who have exhausted any possible treatment with lenalidomide and bortezomib. Carfilzomib, a second-generation proteasome inhibitor, is active as a single agent and in combination with other anti-myeloma agents. Ixazomib is the first oral proteasome inhibitor to be evaluated in myeloma and is associated with a good safety profile and anti-myeloma activity in relapsed/refractory patients, even in those refractory to bortezomib. Monoclonal antibodies and immune checkpoint inhibitors are likely to play a major role in the treatment of myeloma over the next decade. In phase 3 studies, triplet regimens based on these agents combined with a backbone therapy (including lenalidomide, pomalidomide or bortezomib) were more efficacious than doublet regimens in patients with relapsed/refractory multiple myeloma, with limited additional toxic effects. This paper aims to provide an overview of the recent use of these agents for the treatment of myeloma, in particular focusing on the role of multi-agent combinations. PMID:28948001

  10. 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.

  11. 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

  12. Esophageal Distension During Bolus Transport: Can it be Detected by Intraluminal Impedance Recordings?

    PubMed Central

    Kim, Ji Hyun; Mittal, Ravinder K.; Patel, Nirali; Ledgerwood, Melissa; Bhargava, Valmik

    2014-01-01

    Introduction Esophageal multiple intraluminal impedance (MII) measurement has been in used to detect gastroesophageal reflux and bolus transport. It is not clear if MII can detect changes in luminal cross sectional area (CSA) during bolus transport. Aims Intraluminal ultrasound (US) images, MII and high resolution manometry (HRM) were recorded simultaneously to determine temporal relationship between CSA and impedance during esophageal bolus transport and to define the relationship between peak distension and nadir impedance. Methods Studies were conducted in five healthy subjects. MII, HRM and US images were recorded 6 cm above LES. Esophageal distensions were studied during swallows and injections of 0.5 N saline bolus into the esophagus. Results Temporal change in esophageal CSA correlates with changes in impedance (r value: mean ± SD = −0.80 ± 0.08, range: −0.94 to −0.66). Drop in impedance during distension occurs as a two step process; initial large drop associated with onset of CSA increase, followed by a small drop during which majority of the CSA increase occurs. Peak CSA and nadir impedance occur within 1 s of each other. Increase in swallow and injection volumes increased the CSA, had no effect on large drop but increased the small drop amplitude. We observed a significant correlation between peak CSA and nadir impedance (r = − 0.90, p<0.001) and a better correlation between peak CSA and inverse impedance (r = 0.94, p<0.001). Conclusion Further studies are needed to confirm that intraluminal impedance recordings may be used to measure luminal CSA during esophageal bolus transport. PMID:24861157

  13. Esophageal distension during bolus transport: can it be detected by intraluminal impedance recordings?

    PubMed

    Kim, J H; Mittal, R K; Patel, N; Ledgerwood, M; Bhargava, V

    2014-08-01

    Esophageal multiple intraluminal impedance (MII) measurement has been used to detect gastro-esophageal reflux and bolus transport. It is not clear if MII can detect changes in luminal cross sectional area (CSA) during bolus transport. Intraluminal ultrasound (US) images, MII, and high resolution manometry (HRM) were recorded simultaneously to determine temporal relationship between CSA and impedance during esophageal bolus transport and to define the relationship between peak distension and nadir impedance. Studies were conducted in five healthy subjects. MII, HRM, and US images were recorded 6 cm above LES. Esophageal distensions were studied during swallows and injections of 0.5 N saline bolus into the esophagus. Temporal change in esophageal CSA correlates with changes in impedance (r-value: mean ± SD = -0.80 ± 0.08, range: -0.94 to -0.66). Drop in impedance during distension occurs as a two-step process; initial large drop associated with onset of CSA increase, followed by a small drop during which majority of the CSA increase occurs. Peak CSA and nadir impedance occur within 1 s of each other. Increase in swallow and injection volumes increased the CSA, had no effect on large drop but increased the small drop amplitude. We observed a significant correlation between peak CSA and nadir impedance (r = -0.90, p < 0.001) and a better correlation between peak CSA and inverse impedance (r = 0.94, p < 0.001). Further studies are needed to confirm that intraluminal impedance recordings may be used to measure luminal CSA during esophageal bolus transport. © 2014 John Wiley & Sons Ltd.

  14. Combining many multiple alignments in one improved alignment.

    PubMed

    Bucka-Lassen, K; Caprani, O; Hein, J

    1999-02-01

    The fact that the multiple sequence alignment problem is of high complexity has led to many different heuristic algorithms attempting to find a solution in what would be considered a reasonable amount of computation time and space. Very few of these heuristics produce results that are guaranteed always to lie within a certain distance of an optimal solution (given a measure of quality, e.g. parsimony). Most practical heuristics cannot guarantee this, but nevertheless perform well for certain cases. An alignment, obtained with one of these heuristics and with a bad overall score, is not unusable though, it might contain important information on how substrings should be aligned. This paper presents a method that extracts qualitatively good sub-alignments from a set of multiple alignments and combines these into a new, often improved alignment. The algorithm is implemented as a variant of the traditional dynamic programming technique. An implementation of ComAlign (the algorithm that combines multiple alignments) has been run on several sets of artificially generated sequences and a set of 5S RNA sequences. To assess the quality of the alignments obtained, the results have been compared with the output of MSA 2.1 (Gupta et al., Proceedings of the Sixth Annual Symposium on Combinatorial Pattern Matching, 1995; Kececioglu et al., http://www.techfak.uni-bielefeld. de/bcd/Lectures/kececioglu.html, 1995). In all cases, ComAlign was able to produce a solution with a score comparable to the solution obtained by MSA. The results also show that ComAlign actually does combine parts from different alignments and not just select the best of them. The C source code (a Smalltalk version is being worked on) of ComAlign and the other programs that have been implemented in this context are free and available on WWW (http://www.daimi.au.dk/ õcaprani). klaus@bucka-lassen.dk; jotun@pop.bio.au.dk;ocaprani@daimi.au.dk

  15. 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

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

    PubMed

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

    2017-05-03

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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  5. 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

  6. Realistic IVUS image generation in different intraluminal pressures.

    PubMed

    Cardoso, Fernando Mitsuyama; Moraes, Matheus Cardoso; Furuie, Sérgio Shiguemi

    2012-12-01

    Intravascular ultrasound (IVUS) phantoms are important to calibrate and evaluate many IVUS imaging processing tasks. However, phantom generation is never the primary focus of related works; hence, it cannot be well covered, and is usually based on more than one platform, which may not be accessible to investigators. Therefore, we present a framework for creating representative IVUS phantoms, for different intraluminal pressures, based on the finite element method and Field II. First, a coronary cross-section model is selected. Second, the coronary regions are identified to apply the properties. Third, the corresponding mesh is generated. Fourth, the intraluminal force is applied and the deformation computed. Finally, the speckle noise is incorporated. The framework was tested taking into account IVUS contrast, noise and strains. The outcomes are in line with related studies and expected values. Moreover, the framework toolbox is freely accessible and fully implemented in a single platform. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. A case of endobronchial NUT midline carcinoma with intraluminal growth.

    PubMed

    Watanabe, Sho; Hirano, Satoshi; Mine, Sohtaro; Yoshida, Akihiko; Motoi, Toru; Ishii, Satoshi; Naka, Go; Takeda, Yuichiro; Igari, Toru; Sugiyama, Haruhito; Kobayashi, Nobuyuki

    2015-03-01

    NUT midline carcinoma (NMC) is a rare, lethal form of differentiated squamous cell carcinoma characterized by chromosomal rearrangement of the NUT gene. Its highly aggressive nature commonly leads to unresectable and metastatic lesions. We report on a case of endobronchial NMC in a middle-aged man who was treated by bronchoscopic electrocautery followed by Ewing sarcoma-based chemotherapy with concurrent chemoradiotherapy. The patient's disease continued to be stable 31 months after diagnosis. NMC is a challenging disease entity, which is difficult to diagnose and treat, and has a dismal overall survival. Most cases of NMC are widely metastatic or unresectable when diagnosed. This is the first reported case that involves intraluminal tumour growth of NMC and demonstrates the effectiveness of early intensive local therapy aided by bronchoscopic techniques. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. 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.

  13. 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…

  14. 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…

  15. 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.

  16. [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

  17. Intraluminal urethral brachytherapy for recurrence of transitional cell carcinoma of urinary bladder in urethral stump.

    PubMed

    Chakrabarti, Bikramjit; Ghorai, Suman; Ray, Somapriya Basu; Kar, Sanjay Kumar

    2013-03-01

    We report a unique case of successfully performed intraluminal brachytherapy for low volume urethral mucosal recurrence of transitional cell carcinoma urinary bladder, initially treated by transurethral resection of bladder tumor, followed by radical cystectomy. Since the patient was unwilling to undergo any other operational interventions, intraluminal brachytherapy of urethra was attempted. Fluroscopy guided intraluminal HDR brachytherapy using Lumencath(®) catheter under local anesthesia, and remote afterloading system (Nucletron, an Elekta company, Elekta AB, Stockholm, Sweden) was performed. A fraction dose of 7 Gy in seven weekly fractions was prescribed at 0.5 cm from the single applicator. The result was promising in terms of local control and symptomatic relief. Therefore, intraluminal brachytherapy in low volume superficial local disease in urethra may play a potential role, and should be applied when repeated surgery is not feasible due to technical or medical reasons.

  18. Intraluminal urethral brachytherapy for recurrence of transitional cell carcinoma of urinary bladder in urethral stump

    PubMed Central

    Ghorai, Suman; Ray, Somapriya Basu; Kar, Sanjay Kumar

    2013-01-01

    We report a unique case of successfully performed intraluminal brachytherapy for low volume urethral mucosal recurrence of transitional cell carcinoma urinary bladder, initially treated by transurethral resection of bladder tumor, followed by radical cystectomy. Since the patient was unwilling to undergo any other operational interventions, intraluminal brachytherapy of urethra was attempted. Fluroscopy guided intraluminal HDR brachytherapy using Lumencath® catheter under local anesthesia, and remote afterloading system (Nucletron, an Elekta company, Elekta AB, Stockholm, Sweden) was performed. A fraction dose of 7 Gy in seven weekly fractions was prescribed at 0.5 cm from the single applicator. The result was promising in terms of local control and symptomatic relief. Therefore, intraluminal brachytherapy in low volume superficial local disease in urethra may play a potential role, and should be applied when repeated surgery is not feasible due to technical or medical reasons. PMID:23634154

  19. 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.

  20. Glaucoma medication persistence with a fixed combination versus multiple bottles.

    PubMed

    Higginbotham, Eve J; Hansen, Jan; Davis, Elizabeth J; Walt, John G; Guckian, Angela

    2009-10-01

    To determine if prescribing combination therapy versus two or three separate bottles results in greater persistence among patients with glaucoma. Using a retail pharmacy claims database, three glaucoma patient cohorts were defined and followed for 12 months (January 2004 through December 2004). Patients in cohort 1 had a prescription for a single fixed-combination therapy during the month of January 2004. Cohort 2 consisted of patients with prescriptions for a beta-blocker and one other glaucoma product in the same month. Cohort 3 comprised patients with prescriptions filled for three different glaucoma therapies during the first month. A fixed-combination formulation may have been included in cohorts 2 and 3 as well, but was counted as a single bottle. Persistence rate, defined as the percentage of patients who did not discontinue their medication over the 12-month period, was calculated. Cohort 1 (one bottle; n = 14 742) was more persistent than cohort 2 (two bottles; n = 18 411), with 35.3% vs. 27.2% of patients remaining on therapy at the end of the study period (p < 0.0001). Cohort 3 (n = 4826), with three separate bottles per patient, had the lowest percentage remaining on therapy (23.9%; p < 0.0001). Analyses of pharmacy database data are limited by the possibilities of misidentifying newly treated patients or misclassifying added versus switched medications. As the number of separate products used for glaucoma therapy increases, patient persistence decreases. A management regimen requiring as few products as possible may enhance glaucoma patient persistence.

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

    PubMed

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

    2015-10-01

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

  2. 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

  3. 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.

  4. Intraluminal zinc bioavailability - effect of amino acids on zinc solubility

    SciTech Connect

    Jacobs, F.A.; Nelson, L.S. Jr.; Brushmiller, J.G.

    1986-03-01

    Human and bovine milks and simple solutions modeled after milks (milk models) have been used in the development of an intraluminal system involves subjecting a food, i.e., milk, to the pH range encountered in the digestive tract, and measuring the amount of soluble minerals at various pH's. With this system the authors have demonstrated that co-precipitation of zinc with calcium phosphate is a key factor modulating the solubility of zinc in milks and in milk models. Since a mineral must be soluble in order to be bioavailable, and since free amino acids have been suggested to increase the solubility of zinc by adding various amino acids. Of the amino acids, aspartate, glutamate, histidine, and phosphoserine, only histidine (10 mM) increased the solubility of zinc in a milk model, albeit slightly. Supplementation of bovine milk with 10 mM histidine also resulted in a slight increase in zinc solubility. No increase in zinc solubility was observed at a physiologic histidine level. Free amino acids at physiologic concentrations do not increase zinc solubility in milks, and therefore, do not seem to contribute to zinc bioavailability.

  5. 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.

  6. 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

  7. Carrier allocation combined with independent component analysis for multiple-input-multiple-output visible light communication

    NASA Astrophysics Data System (ADS)

    Jiang, Fangqing; Deng, Honggui; Yang, Fang; Zhu, Kaicheng; Zhu, Congxu

    2014-02-01

    We present a scheme based on precoding carrier allocation and independent component analysis (ICA) for indoor multiple-input-multiple-output (MIMO) visible light communication (VLC). In order to improve the reliability of the ICA algorithm for the mixed signal separation, at the sending end, frequency doubled-carriers are employed to module the parallel data which ensure that the modulated signals are independent of each other. The ICA algorithm is applied to separate the mixed signal at the receiving end directly without the requirement of the channel information. Simulation results show that this indoor MIMO VLC scheme can achieve excellent performance. When the signal-to-noise ratio is equal to 14 dB, the bit error ratio (BER) reaches the level of 10-5. So, the communication performance is superior to that of the commonly used schemes based on the channel estimation.

  8. A new combination of multiple autoimmune syndrome? Coexistence of vitiligo, autoimmune thyroid disease and ulcerative colitis.

    PubMed

    Topal, Firdevs; Senel, Engin; Akbulut, Sabiye; Topal, Fatih; Dölek, Yasemin

    2011-08-03

    The occurrence of three or more autoimmune disorders in one patient defines multiple autoimmune syndrome. The pathogenesis of multiple autoimmune syndrome is not known yet and environmental triggers and genetic susceptibility have been suggested to be involved. Herein, we report a 47-year-old woman who had Hashimoto's thyroiditis, vitiligo and newly diagnosed ulcerative colitis. Diagnosis of ulcerative colitis was confirmed with histopathologic examination. This case presents a new combination of multiple autoimmune syndrome.

  9. 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…

  10. Using Discriminant Analysis as a Method of Combining Multiple Measures of Student Performance.

    ERIC Educational Resources Information Center

    Good, Robert

    Current methods of combining multiple measures of student performance have been subjective and have lacked evidence of external validity. This study examined the use of predictive discriminant analysis (PDA) as a means of finding the best combination of variables to predict performance on a standards-based mathematics assessment. Data from 261…

  11. 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.

  12. Medications as causes of intraluminal hyperdensities: what radiologists need to know.

    PubMed

    Sin, Francesca Nga Yee; Tsang, Jane Pui Ki; Siu, Kwong Lok; Ma, Johnny Ka Fai; Yung, Alfred Wei Tak

    2012-07-01

    In computed tomography (CT) angiogram or some dedicated CT studies of the abdomen, the use of positive enteric contrast should be avoided as its presence could decrease the sensitivity of the test. There are, however, cases of CT scans with unexpected hyperdense intraluminal contents detected due to the use of certain oral or rectal medications. Reports on medications as causes of intraluminal hyperdensities are sparse in the English literature. We have studied several commonly used medications and revealed that many drugs appear hyperdense in CT scans. The presence of unexpected intraluminal hyperdensities can potentially cause erroneous interpretation of images and in some cases decrease the sensitivity of the test. The hyperdense bowel contents may be mistaken as acute hemorrhage in CT angiogram for detection of GI bleeding. Active GI bleeding, presented as intraluminal extravasation of contrast material, can also be obscured. Certain intra-abdominal pathologies could be masked, for example, in plain CT scan for detection of urinary tract stones or in contrast CT study for suspected bowel ischaemia. It is important for radiologists and clinicians to be aware of this situation in order to prevent misinterpretation of images and to select the most appropriate imaging modality when such unexpected intraluminal hyperdensities are encountered. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. 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.

  14. 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.

  15. Spatial light structuring using a combination of multiple orthogonal orbital angular momentum beams with complex coefficients.

    PubMed

    Xie, Guodong; Liu, Cong; Li, Long; Ren, Yongxiong; Zhao, Zhe; Yan, Yan; Ahmed, Nisar; Wang, Zhe; Willner, Asher J; Bao, Changjing; Cao, Yinwen; Liao, Peicheng; Ziyadi, Morteza; Almaiman, Ahmed; Ashrafi, Solyman; Tur, Moshe; Willner, Alan E

    2017-03-01

    Analogous to time signals that can be composed of multiple frequency functions, we use uniquely structured orthogonal spatial modes to create different beam shapes. We tailor the spatial structure by judiciously choosing a weighted combination of multiple modal states within an orthogonal orbital angular momentum (OAM) basis set, creating desired beam intensity "shapes." The weights of the OAM beams to be combined forms a Fourier pair with the spatial intensity distribution in the azimuthal direction of the resultant beam. As an example, we simulate and experimentally create various beam shapes by designing the weights of the combined OAM beams. We also find that 6× higher localized power, as compared to traditional beam combining, could be achieved by coherently combining nine orthogonal OAM beams.

  16. [Clinical Efficacy of Cellular Immuotherapy Combined with Bortezomib for the Treatment of Patients with Multiple Myeloma].

    PubMed

    Wang, Yi-Ming; Long, Hao; Yang, Dan; Shao, Jiang-He

    2017-06-01

    To study the clinical efficacy of cellular immunotherapy combined with bortezomib for treatment of patients with multiple myeloma. A total of 76 patients with multiple myeloma in our hospital from October 2012 to October 2013 were selected and randomly divided into 2 groups: the patients in 1 group (38 cases) were treated with cellular immunotherapy combined with chemotherapy including bortezomib (combined therapy group), the patients in other group(38 cases) were treated with only chemotherapy including bortezomib(single chemotherapy as control group). The treatment remission rate, the expression changes of immunophenotype, progression-free survival(PFS) and adverse reactions were compared in the 2 groups. The total remission rate of combined therapy group was significantly higher than that in the control group (P<0.05); the positive rates of CD38(+), CD56(+) and CD138(+) in combined therapy group were all significantly lower than those in control group, and the CD19(+) was significantly higher (P<0.05). The PFS rates of 1, 2 and 3 years in the combined therapy group were all significantly higher than those in the control group (P<0.05). The incidence of fatigue, rash, peripheral neuropathy, anemia and granulocyte deficiency in the combined therapy group was all significantly lower than that in the control group (P<0.05). Cellular immunotherapy combined with bortezomib can significantly improve the remission rate, prolong survival, and significantly decrease adverse event rate of multiple myeloma patients.

  17. 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.

  18. Combining Multiple Algorithms for Road Network Tracking from Multiple Source Remotely Sensed Imagery: a Practical System and Performance Evaluation

    PubMed Central

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

    2009-01-01

    In light of the increasing availability of commercial high-resolution imaging sensors, automatic interpretation tools are needed to extract road features. Currently, many approaches for road extraction are available, but it is acknowledged that there is no single method that would be successful in extracting all types of roads from any remotely sensed imagery. In this paper, a novel classification of roads is proposed, based on both the roads' geometrical, radiometric properties and the characteristics of the sensors. Subsequently, a general road tracking framework is proposed, and one or more suitable road trackers are designed or combined for each type of roads. Extensive experiments are performed to extract roads from aerial/satellite imagery, and the results show that a combination strategy can automatically extract more than 60% of the total roads from very high resolution imagery such as QuickBird and DMC images, with a time-saving of approximately 20%, and acceptable spatial accuracy. It is proven that a combination of multiple algorithms is more reliable, more efficient and more robust for extracting road networks from multiple-source remotely sensed imagery than the individual algorithms. PMID:22399965

  19. 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

  20. Preoperative intraluminal application of capsaicin increases postoperative gastric and colonic motility in rats.

    PubMed

    Zittel, T T; Meile, T; Huge, A; Kreis, M E; Becker, H D; Jehle, E C

    2001-01-01

    In a model to investigate postoperative gastrointestinal motility with strain gauge transducers in awake rats, we tested the effects of intraluminal capsaicin infusion into the cecum 2 days or 14 days prior to abdominal surgery. Acute infusion of capsaicin into the cecum for 30 minutes increased the gastric, small intestinal, and colonic motility index by up to 115%, 34%, and 59%, respectively, compared to vehicle infusion. Intraluminal capsaicin infusion 2 days prior to abdominal surgery significantly increased the intraoperative gastric and colonic motility index by 166% and 100%, respectively, compared to vehicle, but had no effect on small intestinal motility. The postoperative decrease in gastric or colonic motility was completely prevented by capsaicin pretreatment, representing a 73% and a 72% increase in the motility index during the first postoperative hour and a 40% and a 29% increase in the motility index during the second postoperative hour compared to vehicle, whereas the postoperative decrease in small intestinal motility was not altered by capsaicin pretreatment. In contrast, intraluminal capsaicin infusion 14 days prior to abdominal surgery had no effect on postoperative inhibition of gastrointestinal motility. Our results suggest that capsaicin-sensitive visceral afferent C-fibers, presumably of the submucosa, play an important role in mediating postoperative ileus. Intraluminal capsaicin does probably ablate these nerve fibers temporarily, with no systemic side effects observed with the use of the tail flick test as a measure of skin nociception.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. Behavioral profiling in CCTV cameras by combining multiple subtle suspicious observations of different surveillance operators

    NASA Astrophysics Data System (ADS)

    Bouma, Henri; Vogels, Jack; Aarts, Olav; Kruszynski, Chris; Wijn, Remco; Burghouts, Gertjan

    2013-05-01

    Camera surveillance and recognition of deviant behavior is important for the prevention of criminal incidents. A single observation of subtle deviant behavior of an individual may sometimes be insufficient to merit a follow-up action. Therefore, we propose a method that can combine multiple weak observations to make a strong indication that an intervention is required. We analyze the effectiveness of combining multiple observations/tags of different operators, the effects of the tagging instruction these operators received (many tags for weak signals or few tags for strong signals), and the performance of using a semi-automatic system for combining the different observations. The results show that the method can be used to increase hits (detecting criminals) whilst reducing false alarms (bothering innocent passers-by).

  6. 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

  7. Coherent beam combining and optical space-time division multiple access

    NASA Astrophysics Data System (ADS)

    Miniscalco, William; Lane, Steven A.; Fisher, Kirk; Waite, Stephanie; Howlett, Michael; Smith, Irl

    2010-08-01

    We have developed an approach to multiple-access lasercom that adopts the commercial paradigm of sharing the most expensive terminal resources among all users. Space-time division multiple access (STDMA), analogous to an optical space-time switch, hops the transmit beam and receive direction among multiple users and exchanges data while the beam dwells on a user. A key enabler of STDMA is electronic beam steering using liquid crystal optical phased arrays, which provides fast, precise, and agile beam re-pointing. We have built the first optical STDMA terminal, combining beam hopping between remote terminals with coherent combining of both transmit and receive apertures, which is an effective means for increasing antenna gain in systems for which large aperture components are impractical. Coherent beam combining provided the expected increase in antenna gain, and the terminal was found to re-point the beam among users quickly and precisely enough to suffer only minor throughput degradation. Communications test were performed using 10 Gb/s Ethernet for a single-aperture configuration. Performance is presented as a function of angle scan speed and STDMA dwell time per remote terminal. The results suggest that STDMA is a viable technology for supporting multiple-access space-based laser communication.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

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

    NASA Astrophysics Data System (ADS)

    Skoro Kaskarovska, Violeta

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

  15. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. 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.

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

    PubMed

    Choi, Hyo-Rim; Kim, TaeYong

    2017-08-17

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

  18. 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.

  19. [Hepatectomy combined with cryoablation and ethanol injection for unresectable multiple liver metastases from colorectal cancer].

    PubMed

    Lu, Wei-qun; Yu, Nan-rong; Liu, Hai-ying

    2012-04-01

    To evaluate the efficacy and safety of hepatectomy combined with cryoablation and ethanol injection in patients with unresectable multiple liver metastases from colorectal cancer. Clinical data of 23 patients with multiple liver metastases form colorectal cancer in the Affiliated Tumor Hospital of Guangzhou Medical College between January 2005 and December 2010 were analyzed retrospectively. There were 15 males and 8 females with average age of 52.2 years. All the patients underwent hepatectomy combined with ultrasound-guided cryoablation and ethanol injection intraoperatively. Among 98 lesions in 23 patients, 45 were removed intraoperatively and 53 were treated by cryoablation and ethanol injection. Operative time for liver lesions ranged from 27 to 96 minutes and intraoperative blood loss 50 to 450 ml. One patient developed pleural effusion and 1 myoglobinuria after operation. All the patients were followed up with a median follow-up time of 34 months(8 to 70 months). The 1-, 3-, and 5-year survival rates were 83.2%, 45.5% and 37.6% respectively. Hepatectomy combined with cryoablation and ethanol injection is an effective and safe treatment option for patients with unresectable multiple liver metastases from colorectal cancer.

  20. 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.

  1. 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.

  2. 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

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  5. 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

  6. Tracheostomaplasty: A surgical method for improving retention of an intraluminal stoma button for hands-free tracheoesophageal speech.

    PubMed

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

    2010-12-01

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

  7. 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

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

    PubMed

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

    2017-02-01

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

  9. A new method for monitoring oviductal intraluminal pressure changes in the unrestrained sow.

    PubMed

    Henriksson, A; Rodriguez-Martinez, H; Einarsson, S

    1986-05-01

    A new technique, using an intraluminally placed dacron catheter carrying an ultra miniature pressure sensor (MIKRO-TIP, PR-249, Millar Instr., USA) was designed for recording spontaneous intraluminal pressure variations which reflected contractions in the oviductal wall. The catheter was passed subcutaneously from the lumbar back of the animal to the flank where an incision had been made. The distal end of the catheter was passed from a small incision in the uterus tip 2 cm into the isthmus of the oviduct. The catheter's position was secured and control recordings made by connecting the catheter's electrical connector to a polygraph. During the subsequent 24-48 hours successful recordings were made at frequent intervals. Peripheral blood was collected in connection with each recording to monitor ovarian functions.

  10. 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

  11. Intraluminal Injection of Mesenchymal Stromal Cells in Spheroids Attenuates Experimental Colitis.

    PubMed

    Molendijk, Ilse; Barnhoorn, Marieke C; de Jonge-Muller, Eveline S M; Mieremet-Ooms, Marij A C; van der Reijden, Johan J; van der Helm, Danny; Hommes, Daniel W; van der Meulen-de Jong, Andrea E; Verspaget, Hein W

    2016-08-01

    In recent years, mesenchymal stromal cells [MSCs] emerged as a promising therapeutic option for various diseases, due to their immunomodulatory properties. We previously observed that intraperitoneally injected MSCs in experimental colitis form spherical shaped aggregates. Therefore, we aggregated MSCs in vitro into spheroids and injected them intraluminally in mice with established colitis, to investigate whether these MSC spheroids could alleviate the colitis. We injected 0.5 x 10(6) MSCs in spheroids, 2.0 x 10(6) MSCs in spheroids, or phosphate-buffered saline [PBS] as a treatment control, via an enema in mice with established dextran sulphate sodium [DSS]-induced colitis. Body weight was measured daily and disease activity score was determined at sacrifice. Endoscopy was performed to evaluate mucosal healing. After sacrifice, both systemic and local inflammatory responses were evaluated. Intraluminally injected MSC spheroids alleviated DSS-induced colitis, resulting in significantly less body weight loss and lower disease activity score at sacrifice when a high dose of MSC spheroids was administered. However, the percentage of mucosal lesions in the distal colon and endoscopy scores were not significantly lower after treatment with 2.0 x 10(6) MSCs in spheroids compared with PBS-treated mice. Systemic inflammation marker serum amyloid A [SAA] was significantly reduced after treatment with 2.0 x 10(6) MSCs in spheroids. In addition, local cytokine levels of IFN-ɣ, TNF-α, IL-6, and IL-17a, as well as numbers of macrophages and neutrophils, showed a clear decrease-though not always significant-after intraluminal injection of the MSC spheroids. Intraluminally injected MSC spheroids at least partially attenuate experimental colitis, with fewer phagocytes and proinflammmatory cytokines, when a high dose of MSCs in spheroids was administered. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights

  12. Huge ascending aortic aneurysm with an intraluminal thrombus in an embolic event-free patient.

    PubMed

    Parato, Vito Maurizio; Prifti, Edvin; Pezzuoli, Franco; Labanti, Benedetto; Baboci, Arben

    2015-03-01

    We present a case of an 87-year-old male patient with a huge ascending aortic aneurysm, filled by a huge thrombus most probably due to previous dissection. This finding was detected by two-dimensional transthoracic echocardiography and contrast-enhanced computed tomography (CT) angiography scan. The patient refused surgical treatment and was medically treated. Despite the huge and mobile intraluminal thrombus, the patient remained embolic event-free up to 6 years later, and this makes the case unique.

  13. Combining multiple single-reference transmissibility functions in a unique matrix formulation for operational modal analysis

    NASA Astrophysics Data System (ADS)

    Devriendt, C.; Weijtjens, W.; De Sitter, G.; Guillaume, P.

    2013-10-01

    In recent years, the authors have proposed an innovative approach for Operational Modal Analysis based on transmissibility measurements. A method was proposed based on combining 2 single-reference transmissibility functions that were obtained during 2 different loading conditions. However in practice one in general has access to multiple transmissibility functions and perhaps even multiple loading conditions. In this paper a new method is introduced that combines all the measured single-reference transmissibility functions in a unique matrix formulation in order to identify system poles. It will be shown that each element of the pseudo-inverse of this matrix is a rational function with poles equal to the system poles. The proposed method reduces the risk to miss system poles and to identify extra non-physical poles. Therefore the method increases the usability and reliability of transmissibility based operational modal analysis (TOMA). The method will be demonstrated and validated by means of an experiment on a beam excited at multiple inputs for three different loading conditions.

  14. 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.

  15. 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.

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

    PubMed Central

    Saeedi, Ehsan; Kong, Yinan

    2017-01-01

    In this paper, we propose a novel parallel architecture for fast hardware implementation of elliptic curve point multiplication (ECPM), which is the key operation of an elliptic curve cryptography processor. The point multiplication over binary fields is synthesized on both FPGA and ASIC technology by designing fast elliptic curve group operations in Jacobian projective coordinates. A novel combined point doubling and point addition (PDPA) architecture is proposed for group operations to achieve high speed and low hardware requirements for ECPM. It has been implemented over the binary field which is recommended by the National Institute of Standards and Technology (NIST). The proposed ECPM supports two Koblitz and random curves for the key sizes 233 and 163 bits. For group operations, a finite-field arithmetic operation, e.g. multiplication, is designed on a polynomial basis. The delay of a 233-bit point multiplication is only 3.05 and 3.56 μs, in a Xilinx Virtex-7 FPGA, for Koblitz and random curves, respectively, and 0.81 μs in an ASIC 65-nm technology, which are the fastest hardware implementation results reported in the literature to date. In addition, a 163-bit point multiplication is also implemented in FPGA and ASIC for fair comparison which takes around 0.33 and 0.46 μs, respectively. The area-time product of the proposed point multiplication is very low compared to similar designs. The performance (1Area×Time=1AT) and Area × Time × Energy (ATE) product of the proposed design are far better than the most significant studies found in the literature. PMID:28459831

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

    PubMed

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

    2017-01-01

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

  18. The effect of intraluminal contact mediated guidance signals on axonal mismatch during peripheral nerve repair.

    PubMed

    Daly, William T; Yao, Li; Abu-rub, Mohammad T; O'Connell, Claire; Zeugolis, Dimitrios I; Windebank, Anthony J; Pandit, Abhay S

    2012-10-01

    The current microsurgical gold standard for repairing long gap nerve injuries is the autograft. Autograft provides a protective environment for repair and a natural internal architecture, which is essential for regeneration. Current clinically approved hollow nerve guidance conduits allow provision of this protective environment; however they fail to provide an essential internal architecture to the regenerating nerve. In the present study both structured and unstructured intraluminal collagen fibres are investigated to assess their ability to enhance conduit mediated nerve repair. This study presents a direct comparison of both structured and unstructured fibres in vivo. The addition of intraluminal guidance structures was shown to significantly decrease axonal dispersion within the conduit and reduced axonal mismatch of distal nerve targets (p < 0.05). The intraluminal fibres were shown to be successfully incorporated into the host regenerative process, acting as a platform for Schwann cell migration and axonal regeneration. Ultimately the fibres were able to provide a platform for nerve regeneration in a long term regeneration study (16 weeks) and facilitated increased guidance of regenerating axons towards their distal nerve targets. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Effective intraluminal shunt in carotid endarterectomy for carotid artery near occlusion: A technical report.

    PubMed

    Kawamura, Yoichiro; Maruyama, Daisuke; Akagi, Yojiro; Iihara, Koji

    2017-07-21

    Carotid artery near occlusion is a critical degree of stenosis whereby blood flow is decreased and the distal cervical and intracranial internal carotid arteries (ICAs) are prone to collapse. Considering the diminished perfusion and the risk of progression to total occlusion and periocclusive embolism, we performed carotid endarterectomy (CEA) for carotid artery near occlusion. Accurate evaluation of tandem stenosis or patency of the post-stenotic ICA in carotid artery near occlusion is often difficult preoperatively. Thus, we performed CEA in a hybrid operating room where intraoperative digital subtraction angiography (DSA) and endovascular angioplasty or stenting for distal lesions can be performed if necessary. In addition, to evaluate the distal ICA intraoperatively, we used an intraluminal shunt for shunt angiography, with injection of contrast material through the shunt tube, as a replacement for conventional DSA. Furthermore, an intraluminal shunt held the collapsed lumen open and provided a scaffold for suturing, which prevented postoperative stenosis of the distal ICA. The present report is intended to underline the merits of intraluminal shunt as a replacement for conventional DSA and as a scaffold for suturing. Copyright © 2017. Published by Elsevier Inc.

  20. A new technique for intraluminal hollow organ imaging: three-dimensional ultrasound.

    PubMed

    Cavaye, D M; Tabbara, M R; Kopchok, G E; Laas, T E; Cormier, F; White, R A

    1991-10-01

    Intraluminal ultrasound (ILUS) is a new catheter-based system which produces two-dimensional (2D), cross-sectional images of tubular structures. The principle of image acquisition using 5.0 Fr (30 MHz) and 8.0 Fr (20 MHz) ILUS catheters containing ultrasound transducers at the tip, is equally applicable to all tubular or hollow organs. This article illustrates the feasibility of intraluminal imaging of hollow organ structures, and describes computerized three-dimensional (3D) reconstruction of the 2D images, using a PC-based image analysis system. A set (n = 90) of longitudinally aligned, consecutive 2D images was sampled from various organs (canine bladder, urethra, jejunum, esophagus, and trachea) and computer processed to produce 3D images. By adjusting image density threshold and viewing angle, the lumen and wall morphology can be examined in any projection. Possible applications include diagnosis of lumen encroaching pathology, guidance of intraluminal instruments, and assessment of the effects of endoluminal interventions.

  1. 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.

  2. '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.

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

    PubMed

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

    2017-02-14

    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.

  4. 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. © Georg Thieme Verlag KG Stuttgart · New York.

  5. 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

  6. On the influence of wall calcification and intraluminal thrombus on prediction of abdominal aortic aneurysm rupture.

    PubMed

    Barrett, Hilary E; Cunnane, Eoghan M; Hidayat, Hena; O'Brien, Julie M; Moloney, Michael A; Kavanagh, Eamon G; Walsh, Michael T

    2017-09-09

    Parameters other than maximum diameter that predict rupture of abdominal aortic aneurysms (AAAs) may be helpful for risk-benefit analysis in individual patients. The aim of this study was to characterize the biomechanical-structural characteristics associated with AAA walls to better identify the related mechanistic variables required for an accurate prediction of rupture risk. Anterior AAA wall (n = 40) and intraluminal thrombus (ILT; n = 114) samples were acquired from 18 patients undergoing open surgical repair. Biomechanical characterization was performed using controlled circumferential stretching tests combined with a speckle-strain tracking technique to quantify the spatial heterogeneity in deformation and localized strains in the AAA walls containing calcification. After mechanical testing, the accompanying microstructural characteristics of the AAA wall and ILT types were examined using electron microscopy. No significant correlation was found between the AAA diameter and the wall mechanical properties in terms of Cauchy stress (rs = -0.139; P = .596) or stiffness (rs = -0.451; P = .069). Quantification of significant localized peak strains, which were concentrated in the tissue regions surrounding calcification, reveals that peak strains increased by a mean of 174% as a result of calcification and corresponding peak stresses by 18.2%. Four ILT types characteristic of diverse stages in the evolving tissue microstructure were directly associated with distinct mechanical stiffness properties of the ILT and underlying AAA wall. ILT types were independent of geometric factors, including ILT volume and AAA diameter measures (ILT stiffness and AAA diameter [rs = -0.511; P = .074]; ILT stiffness and ILT volume [rs = -0.245; P = .467]). AAA wall stiffness properties are controlled by the load-bearing capacity of the noncalcified tissue portion, and low stiffness properties represent a highly degraded vulnerable wall. The presence of calcification

  7. 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.

  8. 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

  9. 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

  10. 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

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

    SciTech Connect

    Sharma, Devendra; Kaw, Predhiman K.

    2012-11-15

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

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

    PubMed

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

    2016-02-04

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

  13. 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

  14. 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.

  15. 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.

  16. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla

    PubMed Central

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

    2011-01-01

    sources included oligodendrocytes in normal-appearing white matter and activated macrophages/microglia at the edges of white matter lesions. Additionally, in white matter lesions, iron precipitation in aggregates typical of microbleeds was shown by the Perl's staining. Our combined imaging and pathological study shows that multi-gradient echo magnetic resonance imaging is a sensitive technique for the identification of iron in the brain tissue of patients with multiple sclerosis. However, magnetic resonance imaging-identified iron does not necessarily reflect pathology and may also be seen in apparently normal tissue. Iron identification by multi-gradient echo magnetic resonance imaging in diseased tissues can shed light on the pathological processes when coupled with topographical information and patient disease history. PMID:22171355

  17. 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

  18. Exploring brainstem function in multiple sclerosis by combining brainstem reflexes, evoked potentials, clinical and MRI investigations.

    PubMed

    Magnano, Immacolata; Pes, Giovanni Mario; Pilurzi, Giovanna; Cabboi, Maria Paola; Ginatempo, Francesca; Giaconi, Elena; Tolu, Eusebio; Achene, Antonio; Salis, Antonio; Rothwell, John C; Conti, Maurizio; Deriu, Franca

    2014-11-01

    To investigate vestibulo-masseteric (VMR), acoustic-masseteric (AMR), vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes in patients with multiple sclerosis (MS); to relate abnormalities of brainstem reflexes (BSRs) to multimodal evoked potentials (EPs), clinical and Magnetic Resonance Imaging (MRI) findings. Click-evoked VMR, AMR and VCR were recorded from active masseter and sternocleidomastoid muscles, respectively; TCR was recorded from active sternocleidomastoid muscles, following electrical stimulation of the infraorbital nerve. EPs and MRI were performed with standard techniques. Frequencies of abnormal BSRs were: VMR 62.1%, AMR 55.1%, VCR 25.9%, TCR 58.6%. Brainstem dysfunction was identified by these tests, combined into a four-reflex battery, in 86.9% of cases, by EPs in 82.7%, MRI in 71.7% and clinical examination in 37.7% of cases. The sensitivity of paired BSRs/EPs (93.3%) was significantly higher than combined MRI/clinical testing (70%) in patients with disease duration ⩽6.4years. BSR alterations significantly correlated with clinical, EP and MRI findings. The four-BSR battery effectively increases the performance of standard EPs in early detection of brainstem impairment, otherwise undetected by clinical examination and neuroimaging. Multiple BSR assessment usefully supplements conventional testing and monitoring of brainstem function in MS, especially in newly diagnosed patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

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

    2012-01-01

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

  20. 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.

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2017-02-01

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

  3. A computational framework for gene regulatory network inference that combines multiple methods and datasets

    PubMed Central

    2011-01-01

    Background Reverse engineering in systems biology entails inference of gene regulatory networks from observational data. This data typically include gene expression measurements of wild type and mutant cells in response to a given stimulus. It has been shown that when more than one type of experiment is used in the network inference process the accuracy is higher. Therefore the development of generally applicable and effective methodologies that embed multiple sources of information in a single computational framework is a worthwhile objective. Results This paper presents a new method for network inference, which uses multi-objective optimisation (MOO) to integrate multiple inference methods and experiments. We illustrate the potential of the methodology by combining ODE and correlation-based network inference procedures as well as time course and gene inactivation experiments. Here we show that our methodology is effective for a wide spectrum of data sets and method integration strategies. Conclusions The approach we present in this paper is flexible and can be used in any scenario that benefits from integration of multiple sources of information and modelling procedures in the inference process. Moreover, the application of this method to two case studies representative of bacteria and vertebrate systems has shown potential in identifying key regulators of important biological processes. PMID:21489290

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

    NASA Astrophysics Data System (ADS)

    Le Vine, Nataliya

    2016-04-01

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

  5. 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.

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

    PubMed Central

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

    2013-01-01

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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  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. 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

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

    PubMed

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

    2013-06-01

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

  14. 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

  15. 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.

  16. Clinical effects of intensive insulin therapy treating traumatic shock combined with multiple organ dysfunction syndrome.

    PubMed

    Du, Jundong; Liu, Hongming; Liu, Rong; Yao, Yongming; Jiao, Huabo; Zhao, Xiaodong; Yin, Huinan; Li, Zhanliang

    2011-04-01

    The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome (MODS) were investigated. A total of 114 patients with traumatic shock combined with MODS were randomly divided into two groups: control group (n=56) treated with conventional therapy, and intensive insulin therapy group (n=58) treated with conventional therapy plus continuous insulin pumping to control the blood glucose level at range of 4.4-6.1 mmol/L. White blood cells (WBC) counts, prothrombin time (PT), serum creatinine (SCr), alanine aminotransferase (ALT), serum albumin and PaO(2) were measured before and at the day 1, 3, 5, 7 and 14 after treatment. The incidence of gastrointestinal dysfunction, the incidence of MODS, hospital stay and the mortality were also observed and compared. After intensive insulin therapy, the WBC counts, SCr, ALT and PT were significantly reduced (P<0.05), but the level of serum albumin was significantly increased (P<0.05) at the day 3, 5, 7 and 14. In the meantime, the PaO2 was significantly elevated at the day 3, 5 and 7 (P<0.01) after intensive insulin therapy. The incidence of gastrointestinal dysfunction, the incidence of MODS, the length of hospital stay and the mortality were markedly decreased (P<0.01). The results suggest early treatment with intensive insulin therapy is effective for traumatic shock combined with MODS and can decrease the length of hospital stay and the mortality.

  17. Age at onset of multiple sclerosis is correlated to use of combined oral contraceptives and childbirth before diagnosis.

    PubMed

    Holmqvist, Per; Hammar, Mats; Landtblom, Anne-Marie; Brynhildsen, Jan

    2010-12-01

    The aim of this study was to evaluate whether age of onset of multiple sclerosis is related to use of combined oral contraceptives and/or timing of childbirth. The results showed that use of combined oral contraceptives and childbirth before the first multiple sclerosis symptom was correlated to a higher mean age at the onset of the disease. Copyright © 2010. Published by Elsevier Inc.

  18. 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

  19. 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.

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

    PubMed

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

    2012-09-01

    Although it is well known that pain induces changes in autonomic parameters, the extent to which these changes correlate with the experience of pain is under debate. The aim of the present study was to compare a combination of multiple autonomic parameters and each parameter alone in their ability to differentiate among 4 categories of pain intensity. Tonic heat stimuli (1minute) were individually adjusted to induce no pain, low, medium, and high pain in 45 healthy volunteers. Electrocardiogram, photoplethysmogram, and galvanic skin response were recorded, and the following parameters were calculated: heart rate; heart rate variability-high frequency (0.15 to 0.4Hz) spectral power; skin conductance level; number of skin conduction fluctuations; and photoplethysmographic pulse wave amplitude. A combination of parameters was created by fitting an ordinal cumulative logit model to the data and using linear coefficients of the model. Friedman test with post-hoc Wilcoxon test were used to compare between pain intensity categories for every parameter alone and for their linear combination. All of the parameters successfully differentiated between no pain and all other pain categories. However, none of the parameters differentiated between all 3 pain categories (i.e., low and medium; medium and high; low and high). In contrast, the linear combination of parameters significantly differentiated not only between pain and no pain, but also between all pain categories (P<.001 to .02). These results suggest that multiparameter approaches should be further investigated to make progress toward reliable autonomic-based pain assessment. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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

    PubMed

    Stahl, Kolja; Schneider, Michael; Brock, Oliver

    2017-06-17

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

  2. 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

  3. 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

  4. 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

  5. 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.

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

    PubMed Central

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

    2007-01-01

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

  7. Intraluminal thrombus, intraplaque hemorrhage, plaque thickness, and current smoking optimally predict carotid stroke.

    PubMed

    McNally, J Scott; McLaughlin, Michael S; Hinckley, Peter J; Treiman, Scott M; Stoddard, Gregory J; Parker, Dennis L; Treiman, Gerald S

    2015-01-01

    Intraplaque hemorrhage (IPH) is associated with acute and future stroke. IPH is also associated with lumen markers of stroke risk including stenosis, plaque thickness, and ulceration. Whether IPH adds further predictive value to these other variables is unknown. The purpose of this study was to determine whether IPH improves carotid-source stroke prediction. In this retrospective cross-sectional study, patients undergoing stroke workup were imaged with MRI and IPH detection. Seven hundred twenty-six carotid-brain image pairs were analyzed after excluding vessels with noncarotid plaque stroke sources (420) and occlusions (7) or near-occlusions (3). Carotid imaging characteristics were recorded, including percent diameter and mm stenosis, plaque thickness, ulceration, intraluminal thrombus, and IPH. Clinical confounders were recorded, and a multivariable logistic regression model was fitted. Backward elimination was used to determine essential carotid-source stroke predictors with a threshold 2-sided P<0.10. Receiver operating characteristic analysis was performed to determine discriminatory value. Significant predictors of carotid-source stroke included intraluminal thrombus (odds ratio=103.6; P<0.001), IPH (odds ratio=25.2; P<0.001), current smoking (odds ratio=2.78; P=0.004), and thickness (odds ratio=1.24; P=0.020). The final model discriminatory value was excellent (area under the curve=0.862). This was significantly higher than the final model without IPH (area under the curve=0.814), or models using only stenosis as a continuous variable (area under the curve=0.770) or cutoffs of 50% and 70% (area under the curve=0.669), P<0.001. After excluding patients with noncarotid plaque stroke sources, optimal discrimination of carotid-source stroke was obtained with intraluminal thrombus, IPH, plaque thickness, and smoking history but not ulceration and stenosis. © 2014 American Heart Association, Inc.

  8. 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.

  9. 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.

  10. M-Coffee: combining multiple sequence alignment methods with T-Coffee

    PubMed Central

    Wallace, Iain M.; O'Sullivan, Orla; Higgins, Desmond G.; Notredame, Cedric

    2006-01-01

    We introduce M-Coffee, a meta-method for assembling multiple sequence alignments (MSA) by combining the output of several individual methods into one single MSA. M-Coffee is an extension of T-Coffee and uses consistency to estimate a consensus alignment. We show that the procedure is robust to variations in the choice of constituent methods and reasonably tolerant to duplicate MSAs. We also show that performances can be improved by carefully selecting the constituent methods. M-Coffee outperforms all the individual methods on three major reference datasets: HOMSTRAD, Prefab and Balibase. We also show that on a case-by-case basis, M-Coffee is twice as likely to deliver the best alignment than any individual method. Given a collection of pre-computed MSAs, M-Coffee has similar CPU requirements to the original T-Coffee. M-Coffee is a freeware open-source package available from . PMID:16556910

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2016-06-24

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

  13. Combining multiple tools outperforms individual methods in gene set enrichment analyses

    PubMed Central

    Ng, Milica; Wilson, Nicholas J.; Sheridan, Julie M.; Huynh, Huy; Wilson, Michael J.

    2017-01-01

    Abstract Motivation: Gene set enrichment (GSE) analysis allows researchers to efficiently extract biological insight from long lists of differentially expressed genes by interrogating them at a systems level. In recent years, there has been a proliferation of GSE analysis methods and hence it has become increasingly difficult for researchers to select an optimal GSE tool based on their particular dataset. Moreover, the majority of GSE analysis methods do not allow researchers to simultaneously compare gene set level results between multiple experimental conditions. Results: The ensemble of genes set enrichment analyses (EGSEA) is a method developed for RNA-sequencing data that combines results from twelve algorithms and calculates collective gene set scores to improve the biological relevance of the highest ranked gene sets. EGSEA’s gene set database contains around 25 000 gene sets from sixteen collections. It has multiple visualization capabilities that allow researchers to view gene sets at various levels of granularity. EGSEA has been tested on simulated data and on a number of human and mouse datasets and, based on biologists’ feedback, consistently outperforms the individual tools that have been combined. Our evaluation demonstrates the superiority of the ensemble approach for GSE analysis, and its utility to effectively and efficiently extrapolate biological functions and potential involvement in disease processes from lists of differentially regulated genes. Availability and Implementation: EGSEA is available as an R package at http://www.bioconductor.org/packages/EGSEA/. The gene sets collections are available in the R package EGSEAdata from http://www.bioconductor.org/packages/EGSEAdata/. Contacts:monther.alhamdoosh@csl.com.au ormritchie@wehi.edu.au Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27694195

  14. Combining multiple tools outperforms individual methods in gene set enrichment analyses.

    PubMed

    Alhamdoosh, Monther; Ng, Milica; Wilson, Nicholas J; Sheridan, Julie M; Huynh, Huy; Wilson, Michael J; Ritchie, Matthew E

    2017-02-01

    Gene set enrichment (GSE) analysis allows researchers to efficiently extract biological insight from long lists of differentially expressed genes by interrogating them at a systems level. In recent years, there has been a proliferation of GSE analysis methods and hence it has become increasingly difficult for researchers to select an optimal GSE tool based on their particular dataset. Moreover, the majority of GSE analysis methods do not allow researchers to simultaneously compare gene set level results between multiple experimental conditions. The ensemble of genes set enrichment analyses (EGSEA) is a method developed for RNA-sequencing data that combines results from twelve algorithms and calculates collective gene set scores to improve the biological relevance of the highest ranked gene sets. EGSEA's gene set database contains around 25 000 gene sets from sixteen collections. It has multiple visualization capabilities that allow researchers to view gene sets at various levels of granularity. EGSEA has been tested on simulated data and on a number of human and mouse datasets and, based on biologists' feedback, consistently outperforms the individual tools that have been combined. Our evaluation demonstrates the superiority of the ensemble approach for GSE analysis, and its utility to effectively and efficiently extrapolate biological functions and potential involvement in disease processes from lists of differentially regulated genes. EGSEA is available as an R package at http://www.bioconductor.org/packages/EGSEA/ . The gene sets collections are available in the R package EGSEAdata from http://www.bioconductor.org/packages/EGSEAdata/ . monther.alhamdoosh@csl.com.au mritchie@wehi.edu.au. Supplementary data are available at Bioinformatics online.

  15. Intraluminal fiber-optic Doppler imaging catheter for structural and functional optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Li, Xingde; Ko, Tony H.; Fujimoto, James G.

    2001-12-01

    We describe a miniature fiber-optic Doppler imaging catheter for integrated functional and structural optical coherence tomography (OCT) imaging. The Doppler catheter can map blood flow within a vessel as well as image vessel wall structures. A prototype Doppler catheter has been developed and demonstrated for measuring the intraluminal velocity profile in a vessel phantom (conduit). A simple mathematical model is demonstrated to estimate the total flow rate. This estimation technique also enables the spatial range of flow measurements to be extended by approximately two times the normal OCT image-penetration depth. The Doppler OCT catheter could be a powerful device for cardiovascular imaging.

  16. 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

  17. Huge ascending aortic aneurysm with an intraluminal thrombus in an embolic event-free patient

    PubMed Central

    Parato, Vito Maurizio; Pezzuoli, Franco; Labanti, Benedetto; Baboci, Arben

    2015-01-01

    We present a case of an 87-year-old male patient with a huge ascending aortic aneurysm, filled by a huge thrombus most probably due to previous dissection. This finding was detected by two-dimensional transthoracic echocardiography and contrast-enhanced computed tomography (CT) angiography scan. The patient refused surgical treatment and was medically treated. Despite the huge and mobile intraluminal thrombus, the patient remained embolic event-free up to 6 years later, and this makes the case unique. PMID:25838924

  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. Microarray gene expression profiling analysis combined with bioinformatics in multiple sclerosis.

    PubMed

    Liu, Mingyuan; Hou, Xiaojun; Zhang, Ping; Hao, Yong; Yang, Yiting; Wu, Xiongfeng; Zhu, Desheng; Guan, Yangtai

    2013-05-01

    Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis.

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

    PubMed

    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.

  2. Pulsed discharge helium ionization detector with multiple combined bias/collecting electrodes for gas chromatography.

    PubMed

    Cai, Huamin; Stearns, Stanley D

    2013-04-05

    A pulsed discharge ionization detector (PDHID) with multiple combined bias/collecting electrodes (MC-PDHID) has been developed. Unlike most ionization detector designs with only one collecting electrode, the MC-PDHID builds multiple electrodes inside the detector cell. Each electrode serves as both a bias and a collecting electrode, thus gathering more information from the detector cell and improving PDHIP performance. The advantages of the MC-PDHID are: (1) sensitivity is increased by a factor of 2-3 times as compared with a single collecting electrode PDHID; (2) peak symmetry is improved, especially for narrow peaks; (3) it is possible to use a lower helium flow rate without compromising peak tailing; (4) linear dynamic range is increased by an order of magnitude through the calibration of electron and ion response factors; (5) certain groups of compounds can be identified. For example, if a trace amount of water is used as a dopant, the detector can identify alcohols and compounds with a hydrogen bond, since these compounds interact with the water coated on the wall in the detector cell which makes them stay in the detector cell longer than other compounds. In this research, the detector is characterized with different detector temperatures, flow rates, bias electrical potential arrangements, and bias potential polarities. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Combining associative computing and distributed arithmetic methods for efficient implementation of multiple inner products

    NASA Astrophysics Data System (ADS)

    Guevorkian, David; Yli-Pietilä, Timo; Liuha, Petri; Egiazarian, Karen

    2012-02-01

    Many multimedia processing algorithms as well as communication algorithms implemented in mobile devices are based on intensive implementation of linear algebra methods, in particular, implying implementation of a large number of inner products in real time. Among most efficient approaches to perform inner products are the Associative Computing (ASC) approach and Distributed Arithmetic (DA) approach. In ASC, computations are performed on Associative Processors (ASP), where Content-Addressable memories (CAMs) are used instead of traditional processing elements to perform basic arithmetic operations. In the DA approach, computations are reduced to look-up table reads with respect to binary planes of inputs. In this work, we propose a modification of Associative processors that supports efficient implementation of the DA method. Thus, the two powerful methods are combined to further improve the efficiency of multiple inner product computation. Computational complexity analysis of the proposed method illustrates significant speed-up when computing multiple inner products as compared both to the pure ASC method and to the pure DA method as well as to other state-of the art traditional methods for inner product calculation.

  4. Assessment of predictive performance in incomplete data by combining internal validation and multiple imputation.

    PubMed

    Wahl, Simone; Boulesteix, Anne-Laure; Zierer, Astrid; Thorand, Barbara; Avan de Wiel, Mark

    2016-10-26

    Missing values are a frequent issue in human studies. In many situations, multiple imputation (MI) is an appropriate missing data handling strategy, whereby missing values are imputed multiple times, the analysis is performed in every imputed data set, and the obtained estimates are pooled. If the aim is to estimate (added) predictive performance measures, such as (change in) the area under the receiver-operating characteristic curve (AUC), internal validation strategies become desirable in order to correct for optimism. It is not fully understood how internal validation should be combined with multiple imputation. In a comprehensive simulation study and in a real data set based on blood markers as predictors for mortality, we compare three combination strategies: Val-MI, internal validation followed by MI on the training and test parts separately, MI-Val, MI on the full data set followed by internal validation, and MI(-y)-Val, MI on the full data set omitting the outcome followed by internal validation. Different validation strategies, including bootstrap und cross-validation, different (added) performance measures, and various data characteristics are considered, and the strategies are evaluated with regard to bias and mean squared error of the obtained performance estimates. In addition, we elaborate on the number of resamples and imputations to be used, and adopt a strategy for confidence interval construction to incomplete data. Internal validation is essential in order to avoid optimism, with the bootstrap 0.632+ estimate representing a reliable method to correct for optimism. While estimates obtained by MI-Val are optimistically biased, those obtained by MI(-y)-Val tend to be pessimistic in the presence of a true underlying effect. Val-MI provides largely unbiased estimates, with a slight pessimistic bias with increasing true effect size, number of covariates and decreasing sample size. In Val-MI, accuracy of the estimate is more strongly improved by

  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. Multiple field hyperthermia combined with radiotherapy in advanced carcinoma of the breast.

    PubMed

    Engin, K; Tupchong, L; Waterman, F M; Komarnicky, L; Mansfield, C M; Hussain, N; Hoh, L L; McFarlane, J D; Leeper, D B

    1994-01-01

    Extensive recurrences on the chest wall of advanced carcinoma of the breast in 20 patients were treated with multiple field patchwork hyperthermia combined with radiation therapy between 1987-1991. The objective of the study was to evaluate the feasibility, tumour response and complications of treating extensive lesions with multiple, overlapping fields of hyperthermia. All lesions were diffuse encompassing up to 2900 cm2 in area with or without multiple nodules < or = 3 cm deep. All lesions had failed previous therapy with all but three failing previous radiotherapy. Hyperthermia consisted of 282 hyperthermia applicator fields and 357 hyperthermia treatments with external 915 MHz microwaves using commercially available applicators. Hyperthermia applicator fields were defined by the surface 50% SAR distribution of a particular applicator, and hyperthermia fields were abutted to cover the entire tumour bearing area. Radiation therapy consisted of 81 fields to a mean dose of 40 +/- 1 Gy (SE), 88% of fields received between 30 and 50 Gy. The equivalent dose was 42 +/- 1 Gy, based on the linear-quadratic model and alpha/beta = 25 (Fowler 1989). Overlapping hyperthermia fields were separated by an interval of at least three days. Up to four heat sessions per week were required to cover the entire tumour in a rotating fashion. The hyperthermia treatment time was 60 min. Hyperthermia treatments were continued for the duration of radiation therapy. Each hyperthermia applicator field was heated at least once. Patients were exposed to a mean of 14 +/- 3 hyperthermia applicator fields (range of 3-46 fields) and a mean of 18 +/- 3 hyperthermia treatments (range of 6-61) delivered over a mean of 7.5 +/- 0.9 weeks (range of 3-17 weeks). Each field was heated an average of 1.3 times. The tumour complete response rate was 95% with a recurrence rate of 5%. Nevertheless, the mean survival of patients with a complete response was only 10.8 +/- 1.7 months (range of 2-28 months

  9. 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

  10. 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.

  11. Combining Statistical and Geometric Features for Colonic Polyp Detection in CTC Based on Multiple Kernel Learning

    PubMed Central

    Wang, Shijun; Yao, Jianhua; Petrick, Nicholas; Summers, Ronald M.

    2010-01-01

    Colon cancer is the second leading cause of cancer-related deaths in the United States. Computed tomographic colonography (CTC) combined with a computer aided detection system provides a feasible approach for improving colonic polyps detection and increasing the use of CTC for colon cancer screening. To distinguish true polyps from false positives, various features extracted from polyp candidates have been proposed. Most of these traditional features try to capture the shape information of polyp candidates or neighborhood knowledge about the surrounding structures (fold, colon wall, etc.). In this paper, we propose a new set of shape descriptors for polyp candidates based on statistical curvature information. These features called histograms of curvature features are rotation, translation and scale invariant and can be treated as complementing existing feature set. Then in order to make full use of the traditional geometric features (defined as group A) and the new statistical features (group B) which are highly heterogeneous, we employed a multiple kernel learning method based on semi-definite programming to learn an optimized classification kernel from the two groups of features. We conducted leave-one-patient-out test on a CTC dataset which contained scans from 66 patients. Experimental results show that a support vector machine (SVM) based on the combined feature set and the semi-definite optimization kernel achieved higher FROC performance compared to SVMs using the two groups of features separately. At a false positive per scan rate of 5, the sensitivity of the SVM using the combined features improved from 0.77 (Group A) and 0.73 (Group B) to 0.83 (p ≤ 0.01). PMID:20953299

  12. 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

  13. 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).

  14. The Effect of Sparkling Water on Intraluminal Formulation Behavior and Systemic Drug Performance.

    PubMed

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

    2017-09-01

    In the context of mediating intra- and interindividual 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 and 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 toward 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 (ii) an indirect effect (i.e., gastrointestinal motility) of sparkling water, is likely to contribute to this observation. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. 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.

  16. 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

  17. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2010-08-01

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

  19. 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.

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

    PubMed Central

    2011-01-01

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

  1. 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.

  2. Combining multiple ecosystem productivity measurements to constrain carbon uptake estimates in semiarid grasslands and shrublands

    NASA Astrophysics Data System (ADS)

    Maurer, G. E.; Krofcheck, D. J.; Collins, S. L.; Litvak, M. E.

    2016-12-01

    Recent observational and modeling studies have indicated that semiarid ecosystems are more dynamic contributors to the global carbon budget than once thought. Semiarid carbon fluxes, however, are generally small, with high interannual and spatial variability, which suggests that validating their global significance may depend on examining multiple productivity measures and their associated uncertainties and inconsistencies. We examined ecosystem productivity from eddy covariance (NEE), harvest (NPP), and terrestrial biome models (NEPm) at two very similar grassland sites and one creosote shrubland site in the Sevilleta National Wildlife Refuge of central New Mexico, USA. Our goal was to assess site and methodological correspondence in annual carbon uptake, patterns of interannual variability, and measurement uncertainty. One grassland site was a perennial carbon source losing 30 g C m-2 per year on average, while the other two sites were carbon sources or sinks depending on the year, with average net uptake of 5 and 25 g C m-2 per year at the grassland and shrubland site, respectively. Uncertainty values for cumulative annual NEE overlapped between the three sites in most years. When combined, aboveground and belowground annual NPP measurements were 15% higher than annual NEE values and did not confirm a loss of carbon at any site in any year. Despite differences in mean site carbon balance, year-to-year changes in cumulative annual NEE and NPP were similar at all sites with years 2010 and 2013 being favorable for carbon uptake and 2011 and 2012 being unfavorable at all sites. Modeled NEPm data for a number of nearby grid cells reproduced only a fraction of the observed range in carbon uptake and its interannual variability. These three sites are highly similar in location and climate and multiple carbon flux measurements confirm the high interannual variability in carbon flux. The exact magnitude of these fluxes, however, remains difficult to discern.

  3. 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.

  4. [Effectiveness of combined antiretroviral therapy on multiple AIDS-defining illnesses in an HIV seroconverter cohort].

    PubMed

    Ferreros, Inmaculada; Hurtado, Isabel; del Amo, Julia; Muga, Roberto; del Romero, Jorge; García, Patricia; Alastrué, Ignacio; Belda, Josefina; Guevara, Marcela; Pérez, Santiago

    2011-03-01

    Several observational studies support the protective effect of combined antiretroviral therapy (cART) on time to first AIDS-defining event, but the effect on multiple AIDS defining illnesses remains unclear.The aim of this study is to analyse whether the protective effect of cART persists beyond the first AIDS-defining illness. A total of 1938 subjects from GEMES seroconverter cohort have been included. To analyse cART effectiveness, calendar time has been divided into three periods according to antiretroviral availability. A population-averaged proportional hazard model with staggered entries that counted the gap time, and had event-specific baseline risks, was fitted. During follow-up, 1524 (78.6%), 259 (13.4%), 83 (4.3%) and 72 (3.7%) subjects incurred 0, 1, 2, and 3 or more AIDS-defining illnesses, respectively. After adjustment for sex, age at seroconversion and exposure category, the Relative Risk (RR) of AIDS in the cART period was 0.38 (95%CI 0.30-0.48) compared with the 1992-95 period. The RR of the first, second and third AIDS-defining illness in the cART period were 0.40 (95% CI: 0.32-0.50), 0.27 (95% CI: 0.15-0.50) and 0.41 (95% CI: 0.18-0.96) respectively, relative to the reference calendar period when we allowed the odds ratios to vary by the number of prior AIDS-defining events. The relative risk of AIDS, taking all events into account, was 0.32 (95% CI: 0.25-0.40). Intravenous drug users have a higher risk of developing a first episode of AIDS than homosexuals, RR: 2.14 (95% CI: 1.48-3.10). Results indicate that the relative effect of cART appears to be both protective and stable over multiple AIDS-defining illnesses. Analysis of multiple AIDS-defining illnesses improves the precision of the estimated relative risk. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  5. 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

  6. 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.

  7. Intravascular ultrasound versus digital subtraction angiography: direct comparison of intraluminal diameter measurements in pediatric and adolescent imaging.

    PubMed

    Gill, Anne E; Ciszak, Tadi; Braun, Hayley; Hawkins, C Matthew

    2017-04-01

    Intravascular ultrasound (IVUS) allows intraluminal imaging of blood vessels rather than the one-dimensional luminal outline depicted by digital subtraction angiography (DSA). Despite extensive literature in multiple adult vascular diseases, IVUS has not been directly compared to DSA in pediatric and adolescent vascular pathologies. The purpose of this manuscript is to compare absolute luminal diameter measurements obtained via IVUS and DSA during a variety of pediatric endovascular procedures. We conducted a retrospective review of all pediatric and adolescent endovascular procedures from October 2014 to March 2016 in which IVUS and DSA were used. We compared the vessel diameter measurements and analyzed them using SAS software with a paired t-test. There were 102 total measurements (DSA = 56; IVUS = 56; 22 procedures; 20 patients). On average, IVUS measured 0.6 ± 2.1 mm larger than DSA (95% confidence interval [CI] -0.01 to 1.12; P = 0.06; r = 0.90). When venous compression syndrome (May-Thurner, Nutcracker, superior vena cava syndrome) measurements were excluded, IVUS measured 0.7 ± 1.6 mm larger than DSA (95% CI 0.14 to 1.18; P = 0.01; r = 0.93). When venous compression syndrome measurements were evaluated separately, IVUS measured 0.3 ± 3.0 mm larger than DSA (95% CI -1.16 to 1.82; P = 0.65; r = 0.45). Overall, IVUS measurements were slightly larger than DSA measurements in all data subsets. Absolute vessel diameter measurements obtained with IVUS in the pediatric and adolescent population are statistically significantly larger than those obtained using DSA when excluding venous compression syndromes. In venous compression syndromes, IVUS might provide a more accurate representation of vessel compression and diameter than DSA.

  8. Effectively Identifying eQTLs from Multiple Tissues by Combining Mixed Model and Meta-analytic Approaches

    PubMed Central

    Choi, Ted; Eskin, Eleazar

    2013-01-01

    Gene expression data, in conjunction with information on genetic variants, have enabled studies to identify expression quantitative trait loci (eQTLs) or polymorphic locations in the genome that are associated with expression levels. Moreover, recent technological developments and cost decreases have further enabled studies to collect expression data in multiple tissues. One advantage of multiple tissue datasets is that studies can combine results from different tissues to identify eQTLs more accurately than examining each tissue separately. The idea of aggregating results of multiple tissues is closely related to the idea of meta-analysis which aggregates results of multiple genome-wide association studies to improve the power to detect associations. In principle, meta-analysis methods can be used to combine results from multiple tissues. However, eQTLs may have effects in only a single tissue, in all tissues, or in a subset of tissues with possibly different effect sizes. This heterogeneity in terms of effects across multiple tissues presents a key challenge to detect eQTLs. In this paper, we develop a framework that leverages two popular meta-analysis methods that address effect size heterogeneity to detect eQTLs across multiple tissues. We show by using simulations and multiple tissue data from mouse that our approach detects many eQTLs undetected by traditional eQTL methods. Additionally, our method provides an interpretation framework that accurately predicts whether an eQTL has an effect in a particular tissue. PMID:23785294

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

    NASA Astrophysics Data System (ADS)

    Siklér, Ferenc

    2017-08-01

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

  10. 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

  11. 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

  12. Combining multiple continuous tests for the diagnosis of kidney impairment in the absence of a gold standard

    PubMed Central

    Yu, Binbing; Zhou, Chuan; Bandinelli, Stefania

    2011-01-01

    SUMMARY Receiver Operating Characteristic (ROC) curves are commonly used to summarize the classification accuracy of diagnostic tests. It is not uncommon in medical practice that multiple diagnostic tests are routinely performed or multiple disease markers are available for the same individuals. When the true disease status is verified by a gold standard test, a variety of methods have been proposed to combine such potential correlated tests to increase the accuracy of disease diagnosis. In this article, we propose a method of combining multiple diagnostic tests in the absence of a gold standard. We assume that the test values and their classification accuracies are dependent on covariates. Simulation studies are performed to examine the performance of the combination method. The proposed method is applied to data from a population-based aging study to compare the accuracy of three screening tests for kidney function and to estimate the prevalence of moderate kidney impairment. PMID:21432889

  13. Pharmacokinetics of intraluminally administered serum papaverine for spasm prophylaxis of the internal mammary artery.

    PubMed

    Kiessling, Arndt-Holger; Romasku, Deniss; Beiras-Fernandez, Andres; Ferreirós, Nerea; Labocha, Sandra; Moritz, Anton; Rastan, Ardawan Julian

    2013-10-01

    Papaverine (Paveron N™ Linden Arzneimittel Vertrieb GmbH, Germany) is a widely used agent for preventing spasm in mammary artery preparations. The question addressed in this study is whether the intraluminal administration of papaverine can result in detectable absorption of the drug into the systemic arterial circulation. In 15 patients (age 65 ± 6 years; body mass index 28.9 ± 3.7), an internal mammary artery (IMA) was prepared during coronary artery bypass grafting (CABG). A maximum of 3 mL of a 1 mg/1 mL diluted papaverine solution was injected intravascularly (intraluminally) for spasm prophylaxis. The IMA was closed proximally and distally with bulldog clamps. Blood samples were taken immediately after administration (T1), after 20 minutes (T2), and at the end of the operation (T3). Samples were measured in a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system consisting of a binary pump from Agilent (Waldbronn, Germany) coupled to a high-throughput screening (HTS) PAL injection system (CTC, Zwingen, Switzerland) and a tandem mass spectrometer (API 4000, AB Sciex, Darmstadt, Germany). Papaverine was analyzed in positive mode using an electrospray ion source. Quantitation was performed using Analyst 1.5 software (AB Sciex, Darmstadt, Germany). The newly developed LC-MS/MS method was successfully established for the detection of papaverine in plasma samples. The highest plasma papaverine levels were determined at time point T1 (mean 54.7 ± 39 ng/mL, range 16.6-179 ng/mL). The concentration was already halved 20 minutes after administration (T2) (mean 23.3 ± 2 ng/mL, range 4.6-118 ng/mL). Because of the short half-life and the hemodilution in the extracorporeal circulation, at the end of the operation papaverine (T3) had already fallen to just above the limit of detection (mean 4.1 ± 3.9 ng/mL, range 1.3-16.9 ng/mL). At time point T1, a significant negative correlation was determined between plasma levels and systemic diastolic, but not

  14. Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures.

    PubMed

    Cohn Yakubovich, Doron; Sheyn, Dmitriy; Bez, Maxim; Schary, Yeshai; Yalon, Eran; Sirhan, Afeef; Amira, May; Yaya, Alin; De Mel, Sandra; Da, Xiaoyu; Ben-David, Shiran; Tawackoli, Wafa; Ley, Eric J; Gazit, Dan; Gazit, Zulma; Pelled, Gadi

    2017-03-09

    A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures. The combination of human MSCs (hMSCs) and a clinically relevant PTH dose was studied using immunosuppressed rats. Segmental defects were created in animals' fifth and sixth ribs. The rats were divided into four groups: a negative control group, in which animals received vehicle alone; the PTH-only group, in which animals received daily subcutaneous injections of 4 μg/kg teriparatide, a pharmaceutical derivative of PTH; the hMSC-only group, in which each animal received five injections of 2 × 10(6) hMSCs; and the hMSC + PTH group, in which animals received both treatments. Longitudinal in vivo monitoring of bone formation was performed biweekly using micro-computed tomography (μCT), followed by histological analysis. Fluorescently-dyed hMSCs were counted using confocal microscopy imaging of histological samples harvested 8 weeks after surgery. PTH significantly augmented the number of hMSCs that homed to the fracture site. Immunofluorescence of osteogenic markers, osteocalcin and bone sialoprotein, showed that PTH induced cell differentiation in both exogenously administered cells and resident cells. μCT scans revealed a significant increase in bone volume only in the hMSC + PTH group, beginning by the 4(th) week after surgery. Eight weeks after surgery, 35% of ribs in the hMSC + PTH group had complete bone bridging, whereas there was complete bridging in only 6.25% of ribs (one rib) in the PTH-only group and in none of the ribs in the other groups. Based on the μCT scans, biomechanical analysis using the micro-finite element method demonstrated that

  15. Combining Multiple Resting-State fMRI Features during Classification: Optimized Frameworks and Their Application to Nicotine Addiction

    PubMed Central

    Ding, Xiaoyu; Yang, Yihong; Stein, Elliot A.; Ross, Thomas J.

    2017-01-01

    Machine learning techniques have been applied to resting-state fMRI data to predict neurological or neuropsychiatric disease states. Existing studies have used either a single type of resting-state feature or a few feature types (<4) in the prediction model. However, resting-state data can be processed in many different ways, yielding different feature types containing complementary and/or novel information, leaving uncertain the most informative features to provide to the classifier. In this study, multiple resting-state features were calculated from two main analytical categories: local measures and network measures. Feature selection was adopted using an optimized grid-search approach selecting top ranked features from statistical tests. We then tested three optimized frameworks: feature combination, kernel combination, and classifier combination, all using the support vector machine as an elementary classifier, to combine these resting-state feature types. When applied to nicotine addiction, with a cohort size of 100 smokers and 100 non-smokers, via a 10-fold cross-validation procedure, the feature combination and the classifier combination achieved an accuracy of 75.5%, while the kernel combination achieved a 73.0% accuracy; all three combination frameworks improved classification performance compared to the single feature type based results (best accuracy 70.5%). This study not only reveals the discriminative power of resting-state data, but also demonstrates the efficiency of combining multiple features from one data phenotype to improve classification performance. PMID:28747877

  16. Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

    PubMed Central

    Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

    2014-01-01

    Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

  17. Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen.

    PubMed

    Araya, Romina E; Jury, Jennifer; Bondar, Constanza; Verdu, Elena F; Chirdo, Fernando G

    2014-01-01

    Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.

  18. 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

  19. Imaging of patellar cartilage with a 2D multiple-echo data image combination sequence.

    PubMed

    Schmid, Marius R; Pfirrmann, Christian W A; Koch, Peter; Zanetti, Marco; Kuehn, Bernd; Hodler, Juerg

    2005-06-01

    We sought to evaluate the diagnostic value of a 2D multiple-echo data image combination (MEDIC) MRI sequence in the detection of patellar cartilage defects. Our study included 52 consecutive patients who had knee surgery within 4 months of undergoing an MRI examination including an axial 2D MEDIC (TR/TE, 884/26; flip angle, 30 degrees ) sequence. Cartilage was surgically graded on a 5-point scale: 0, normal; 1, softening or swelling; 2, partial thickness defect; 3, fissuring to the level of the subchondral bone; or 4, exposed subchondral bone. Cartilage was graded on MRI according to a scale that was almost identical to the surgical scale except that grade 1 lesions were defined as signal alteration or swelling of cartilage. Two blinded reviewers independently analyzed patellar cartilage. Sensitivity, specificity, accuracy, and weighted kappa values for interobserver variability were calculated. Low-grade cartilage lesions predominated in our study group. When grade 2 or higher was considered the threshold for relevance, the sensitivity, specificity, and accuracy for the MEDIC sequence was as high as 79%, 82%, and 81%, respectively. Increasing the threshold of relevance to grade 3 increased the sensitivity, specificity, and accuracy to as high as 83%, 91%, and 90%, respectively. Interobserver agreement for the MEDIC sequence was good (weighted kappa = 0.68). The 2D MEDIC sequence performs comparably to previously described sequences optimized for cartilage imaging such as the 3D double-echo steady-state or 3D spoiled gradient-recalled sequences with good interobserver agreement, high sensitivity, and excellent specificity for revealing low- to intermediate-degree cartilage defects.

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  1. 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

    2017-10-10

    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.

  2. On combining multiple features for cartoon character retrieval and clip synthesis.

    PubMed

    Yu, Jun; Liu, Dongquan; Tao, Dacheng; Seah, Hock Soon

    2012-10-01

    How do we retrieve cartoon characters accurately? Or how to synthesize new cartoon clips smoothly and efficiently from the cartoon library? Both questions are important for animators and cartoon enthusiasts to design and create new cartoons by utilizing existing cartoon materials. The first key issue to answer those questions is to find a proper representation that describes the cartoon character effectively. In this paper, we consider multiple features from different views, i.e., color histogram, Hausdorff edge feature, and skeleton feature, to represent cartoon characters with different colors, shapes, and gestures. Each visual feature reflects a unique characteristic of a cartoon character, and they are complementary to each other for retrieval and synthesis. However, how to combine the three visual features is the second key issue of our application. By simply concatenating them into a long vector, it will end up with the so-called "curse of dimensionality," let alone their heterogeneity embedded in different visual feature spaces. Here, we introduce a semisupervised multiview subspace learning (semi-MSL) algorithm, to encode different features in a unified space. Specifically, under the patch alignment framework, semi-MSL uses the discriminative information from labeled cartoon characters in the construction of local patches where the manifold structure revealed by unlabeled cartoon characters is utilized to capture the geometric distribution. The experimental evaluations based on both cartoon character retrieval and clip synthesis demonstrate the effectiveness of the proposed method for cartoon application. Moreover, additional results of content-based image retrieval on benchmark data suggest the generality of semi-MSL for other applications.

  3. Intraluminal fiber-optic Doppler imaging catheter for structural and functional optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Li, Xing D.; Ko, Tony H.; Fujimoto, James G.

    2002-06-01

    A miniature fiber Doppler imaging catheter for integrated functional and structural optical coherence tomography (OCT) imaging has been developed. The Doppler catheter can be used to map blood flow profile within a vessel as well as image vessel wall structures. The prototype Doppler catheter was demonstrated in measuring the intraluminal velocity profile in a vessel phantom (conduit). A simple mathematical model can be used to estimate the flow profile outside of normal OCT beam penetration. By extending the spatial range of the flow measurements to approximately two times the normal OCT image penetration depth, the total flow rate can then be calculated from the estimated velocity profiles. The measured total flow rate in the vessel phantom obtained from the Doppler imaging catheter correlates well with the calibrated flow values. The Doppler OCT catheter's ability to simultaneously obtain both structural and functional information makes it a potentially powerful device of cardiovascular imaging.

  4. 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.

  5. Intraluminal containment of commensal outgrowth in the gut during infection-induced dysbiosis

    PubMed Central

    Molloy, Michael J.; Grainger, John R.; Bouladoux, Nicolas; Hand, Timothy W.; Naik, Shruti; Quinones, Mariam; Dzutsev, Amiran K.; Gao, Ji-Liang; Trinchieri, Giorgio; Murphy, Philip M.; Belkaid, Yasmine

    2016-01-01

    Shifts in the composition of the commensal microbiota are emerging as a hallmark of gastrointestinal inflammation. In particular, outgrowth of γ-proteobacteria has been linked to the etiology of inflammatory bowel disease and the pathologic consequences of infections. Here we show that, following gastrointestinal infection, control of commensal outgrowth is a highly coordinated process involving both the host response and microbial signals. Notably, neutrophil emigration to the lumen results in the generation of organized intra-luminal structures that encapsulate commensals and limit their contact with the epithelium. Formation of these luminal casts depends upon the high-affinity N-formyl peptide receptor, Fpr1. Consequently, after infection, mice deficient in Fpr1 display increased microbial translocation, poor commensal containment and increased mortality. Altogether, our present study describes a novel mechanism by which the host rapidly contains outgrowth of commensal pathobionts during infection. Further, these results reveal Fpr1 as a major mediator of host commensal interaction during dysbiosis. PMID:24034617

  6. 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.

  7. The Abdominal Aortic Aneurysm and Intraluminal Thrombus: Current Concepts of Development and Treatment

    PubMed Central

    Piechota-Polanczyk, Aleksandra; Jozkowicz, Alicja; Nowak, Witold; Eilenberg, Wolf; Neumayer, Christoph; Malinski, Tadeusz; Huk, Ihor; Brostjan, Christine

    2015-01-01

    The pathogenesis of the abdominal aortic aneurysm (AAA) shows several hallmarks of atherosclerotic and atherothrombotic disease, but comprises an additional, predominant feature of proteolysis resulting in the degradation and destabilization of the aortic wall. This review aims to summarize the current knowledge on AAA development, involving the accumulation of neutrophils in the intraluminal thrombus and their central role in creating an oxidative and proteolytic environment. Particular focus is placed on the controversial role of heme oxygenase 1/carbon monoxide and nitric oxide synthase/peroxynitrite, which may exert both protective and damaging effects in the development of the aneurysm. Treatment indications as well as surgical and pharmacological options for AAA therapy are discussed in light of recent reports. PMID:26664891

  8. 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

  9. Sutureless cholecystojejunostomy in pigs using an absorbable intraluminal stent and fibrin glue.

    PubMed

    Detweiler, M B; Verbo, A; Marino, I R; Kobos, J W; Granone, P; Magistrelli, P; Picciocchi, A

    1996-01-01

    The absence of foreign bodies in sutureless anastomoses provides faster healing. The first sutureless cholecystojejunostomies were reported by Murphy in 1892. The common bile duct was tied and 11 cholecystojejunostomies plus 12 jejunojejunostomies were performed in 12 Landrace pigs employing sliding absorbable intraluminal nontoxic stents (SAINTs) and fibrin glue. One cholecystojejunostomy was not performed owing to a gallbladder morphologic anomaly. Three animals died of problems unrelated to the SAINT-glue anastomoses. Of the 18 anastomoses in the 9 remaining animals, all were patent at the verification times of 14, 30, 120, and 480 days. Morphologically,there was greater edema and reduced height of the glandular epithelium in the 30-day CJs when compared to the jejunojejunal anastomoses. Results indicate that the sutureless SAINT-fibrin glue procedure is quite versatile and may be utilized for cholecystoenteric anastomoses.

  10. 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.

  11. 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

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

    PubMed Central

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

    2010-01-01

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

  13. Short-duration increases in intraluminal pressure improve vasoconstrictor responses in aged skeletal muscle feed arteries.

    PubMed

    Seawright, John W; Trache, Andreea; Wilson, Emily; Woodman, Christopher R

    2016-05-01

    We tested the hypothesis that exposure to a short-duration (1 h) increase in intraluminal pressure, to mimic pressure associated with a bout of exercise, would attenuate age-induced impairments of vascular smooth muscle (VSM) constrictor responses in soleus muscle feed arteries (SFA) via the Rho pathway. SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated and pressurized to 90 or 130 cmH2O for 1 h. Following the 1-h treatment, pressure in P130 arteries was lowered to 90 cmH2O for examination of vasoconstrictor responses to norepinephrine (NE), angiotensin II (Ang II), and phenylephrine (PE). To assess the role of the Rho pathway, vasoconstrictor responses were assessed in the absence or presence of a RhoA-kinase inhibitor (Y27632) or RhoA-kinase activator (LPA). Vasoconstrictor responses to NE, Ang II, and PE were impaired in old P90 SFA. Pretreatment of old SFA with increased pressure improved vasoconstrictor responses to NE, PE and Ang II. The beneficial effect of the pressure pretreatment in old SFA was eliminated in the presence of Y27632. In the presence of LPA, vasoconstrictor responses to Ang II were improved in old SFA such that responses were not different than young P90 SFA. These results indicate that a short-duration exposure to increased intraluminal pressure, to mimic pressure associated with a bout of exercise, attenuates or reverses the age-related decrement in VSM constrictor responses in SFA and that the beneficial response is mediated through Rho kinase.

  14. High-efficiency multiple-light-source red-green-blue power combiner with optical waveguide mode coupling technique

    NASA Astrophysics Data System (ADS)

    Sakamoto, J.; Katayose, S.; Watanabe, K.; Itoh, M.; Hashimoto, T.

    2017-02-01

    We propose a very low loss multiple-light-source red-green-blue (RGB) power combiner by optical waveguide mode coupling technique. The combiner consists of a two-step circuit that performs both power coupling and wavelength multiplexing for an RBG multiple-light source. The first step of the circuit combines first R, G, and B as the 0th-order mode. The second step combines second R and G by mode conversion from the 0th-order mode to second-order modes using waveguide mode couplers. We used an even mode configuration to avoid asymmetric deformation of the beam due to interference between the modes. By using all of these coupler functions in the two steps, the circuit provides multiplelight-source (RRGGB) power combining. The combiner was fabricated by silica planar lightwave circuit (PLC) technology. The coupler length is about 4.5 mm, including 2.3 mm for the 0th-order coupler and 2 mm for the secondorder coupler. We estimated the coupling loss of both the 0th-order RGB coupler and second-order RG power coupler to be about 1 dB by evaluating the combined power for the 0th-order RGB couplers and the complementary output powers for mode couplers. To the best of our knowledge, this is the first demonstration of a multiple-light-source RRGGB power combiner using multimode coupling. This method enables us to combine a much larger number of light sources using multi-stage coupling for different modes as well. Moreover, the beam shape can be controlled by mode selection.

  15. 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…

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

    PubMed Central

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

    2014-01-01

    Purpose To compare a novel combined acquisition technique (CAT) of turbo-spin-echo (TSE) and echo-planar-imaging (EPI) with conventional TSE. CAT reduces the electromagnetic energy load transmitted for spin excitation. This radiofrequency (RF) burden is limited by the specific absorption rate (SAR) for patient safety. SAR limits restrict high-field MRI applications, in particular. Material and Methods The study was approved by the local Medical Ethics Committee. Written informed consent was obtained from all participants. T2- and PD-weighted brain images of n = 40 Multiple Sclerosis (MS) patients were acquired by CAT and TSE at 3 Tesla. Lesions were recorded by two blinded, board-certificated neuroradiologists. Diagnostic equivalence of CAT and TSE to detect MS lesions was evaluated along with their SAR, sound pressure level (SPL) and sensations of acoustic noise, heating, vibration and peripheral nerve stimulation. Results Every MS lesion revealed on TSE was detected by CAT according to both raters (Cohen’s kappa of within-rater/across-CAT/TSE lesion detection κCAT = 1.00, at an inter-rater lesion detection agreement of κLES = 0.82). CAT reduced the SAR burden significantly compared to TSE (p<0.001). Mean SAR differences between TSE and CAT were 29.0 (±5.7) % for the T2-contrast and 32.7 (±21.9) % for the PD-contrast (expressed as percentages of the effective SAR limit of 3.2 W/kg for head examinations). Average SPL of CAT was no louder than during TSE. Sensations of CAT- vs. TSE-induced heating, noise and scanning vibrations did not differ. Conclusion T2−/PD-CAT is diagnostically equivalent to TSE for MS lesion detection yet substantially reduces the RF exposure. Such SAR reduction facilitates high-field MRI applications at 3 Tesla or above and corresponding protocol standardizations but CAT can also be used to scan faster, at higher resolution or with more slices. According to our data, CAT is no more uncomfortable than TSE scanning. PMID

  17. In silico identification of breast cancer genes by combined multiple high throughput analyses.

    PubMed

    Shen, Dejun; He, Jianbo; Chang, Helena R

    2005-02-01

    that the combined multiple high throughput analyses is an effective data mining strategy in cancer gene identification. This approach may improve the usage of public available genomic data through strategic data mining of high throughput analysis.

  18. Combined acquisition technique (CAT) for neuroimaging of multiple sclerosis at low specific absorption rates (SAR).

    PubMed

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

    2014-01-01

    To compare a novel combined acquisition technique (CAT) of turbo-spin-echo (TSE) and echo-planar-imaging (EPI) with conventional TSE. CAT reduces the electromagnetic energy load transmitted for spin excitation. This radiofrequency (RF) burden is limited by the specific absorption rate (SAR) for patient safety. SAR limits restrict high-field MRI applications, in particular. The study was approved by the local Medical Ethics Committee. Written informed consent was obtained from all participants. T2- and PD-weighted brain images of n = 40 Multiple Sclerosis (MS) patients were acquired by CAT and TSE at 3 Tesla. Lesions were recorded by two blinded, board-certificated neuroradiologists. Diagnostic equivalence of CAT and TSE to detect MS lesions was evaluated along with their SAR, sound pressure level (SPL) and sensations of acoustic noise, heating, vibration and peripheral nerve stimulation. Every MS lesion revealed on TSE was detected by CAT according to both raters (Cohen's kappa of within-rater/across-CAT/TSE lesion detection κCAT = 1.00, at an inter-rater lesion detection agreement of κLES = 0.82). CAT reduced the SAR burden significantly compared to TSE (p<0.001). Mean SAR differences between TSE and CAT were 29.0 (± 5.7) % for the T2-contrast and 32.7 (± 21.9) % for the PD-contrast (expressed as percentages of the effective SAR limit of 3.2 W/kg for head examinations). Average SPL of CAT was no louder than during TSE. Sensations of CAT- vs. TSE-induced heating, noise and scanning vibrations did not differ. T2-/PD-CAT is diagnostically equivalent to TSE for MS lesion detection yet substantially reduces the RF exposure. Such SAR reduction facilitates high-field MRI applications at 3 Tesla or above and corresponding protocol standardizations but CAT can also be used to scan faster, at higher resolution or with more slices. According to our data, CAT is no more uncomfortable than TSE scanning.

  19. A combined superiority and non-inferiority approach to multiple endpoints in clinical trials.

    PubMed

    Bloch, Daniel A; Lai, Tze Leung; Su, Zheng; Tubert-Bitter, Pascale

    2007-03-15

    Treatment comparisons in clinical trials often involve multiple endpoints. By making use of bootstrap tests, we develop a new non-parametric approach to multiple-endpoint testing that can be used to demonstrate non-inferiority of a new treatment for all endpoints and superiority for some endpoint when it is compared to an active control. It is shown that this approach does not incur a large multiplicity cost in sample size to achieve reasonable power and that it can incorporate complex dependencies in the multivariate distributions of all outcome variables for the two treatments via bootstrap resampling. Copyright (c) 2006 John Wiley & Sons, Ltd.

  20. Multiplicity

    DTIC Science & Technology

    1991-04-01

    practice as a "[descent] into that inner circle of the Inferno where the damned endlessly degate multiplicity for sentencing." United States v. Barnard...select the charges to be brought in a particular case"). 19 Brown v. Ohio, 432 U.S. 161, 165 (1977). 20 Whalen v. United States, 445 U.S. at 689. 21...parte Lange, 8-5 U.S. (19 Wall.) 163 (1874). Cf. Brown v. Ohio, 432 U.S. at 165 ("once the legislature has acted courts may not impose more than one

  1. 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.

  2. Esophageal intraluminal baseline impedance differentiates gastroesophageal reflux disease from functional heartburn.

    PubMed

    Kandulski, Arne; Weigt, Jochen; Caro, Carlos; Jechorek, Doerthe; Wex, Thomas; Malfertheiner, Peter

    2015-06-01

    Mucosal integrity can be assessed in patients with gastroesophageal reflux disease (GERD) by measuring intraluminal baseline impedance (BI). However, it is not clear whether BI is abnormal in patients with functional heartburn (FH), or can be used to distinguish them from patients with GERD. We compared differences in BI between patients with FH vs GERD. We performed a prospective study of 52 patients (16 men; mean age, 55 y; range, 23-78 y) seen at a tertiary university hospital from February 2009 through December 2012. Thirty-five patients had GERD (19 had nonerosive reflux disease [NERD], 16 had erosive reflux disease [ERD]) and 17 had FH. All patients discontinued proton pump inhibitor therapy and then underwent esophagogastroduodenoscopy and multichannel intraluminal impedance and pH monitoring. BI was assessed at 3, 5, 7, 9, 15, and 17 cm proximal to the lower esophageal sphincter in recumbent patients. Biopsy specimens were taken from 3 cm above the gastroesophageal junction; histology analysis was performed to identify and semiquantitatively score (scale, 0-3) dilated intercellular spaces. Baseline impedance in the distal esophagus was significantly lower in patients with NERD or erosive reflux disease (ERD) than FH (P = .0006). At a cut-off value of less than 2100 Ω, BI measurements identified patients with GERD with 78% sensitivity and 71% specificity, with positive and negative predictive values of 75%. Also in the proximal esophagus, reduced levels of BI levels were found only in patients with ERD. There were negative correlations between level of BI and acid exposure time (r = -0.45; P = .0008), number of acidic reflux episodes (r = -0.45; P = .001), and proximal extent (r = -0.40; P = .004). Biopsy specimens from patients with NERD or ERD had significant increases in dilation of intercellular spaces, compared with those from patients with FH; there was an inverse association between dilated intercellular spaces and BI in the distal esophagus

  3. Single-pill triple-combination therapy: an alternative to multiple-drug treatment of hypertension.

    PubMed

    Chrysant, Steven G

    2011-11-01

    Hypertension (HTN) affects an estimated 76.4 million US adults. Despite improvements in blood pressure (BP) control rates and the availability of effective antihypertensive agents, only 50% of these individuals achieve BP control. It is now recognized that many patients will require ≥ 2 antihypertensive agents to achieve BP control. Both the current US and reappraisal of the 2007 European guidelines include dual-combination regimens among recommended treatments for initial HTN therapy. For patients requiring 3 drugs, the combination of agents with complementary mechanisms of action (ie, renin-angiotensin-aldosterone system blocker, calcium channel blocker, and diuretic) has been recognized as rational and effective. Three single-pill triple-drug combinations have recently been approved for use in HTN in the United States: valsartan (VAL)/amlodipine (AML)/hydrochlorothiazide (HCTZ); olmesartan medoxomil (OM)/AML/HCTZ; and aliskiren (ALI)/VAL/HCTZ. Triple-combination regimens have resulted in a greater proportion of patients achieving BP control compared with dual-combination regimens, with significantly lower BP levels documented after only 2 weeks at maximum doses. Single-pill combinations offer convenience to address barriers to BP control such as poor adherence to therapy and therapeutic inertia. Additional benefits of combining antihypertensive agents from different classes include improved efficacy, safety, and reduction of cardiovascular risk. In patients with essential HTN for whom dual therapy is inadequate, single-pill triple-drug therapy can offer a simplified and effective treatment strategy.

  4. 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…

  5. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  7. 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...

  8. 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…

  9. 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...

  10. Combined (1)H and (31)P spectroscopy provides new insights into the pathobiochemistry of brain damage in multiple sclerosis.

    PubMed

    Hattingen, Elke; Magerkurth, Jörg; Pilatus, Ulrich; Hübers, Annemarie; Wahl, Mathias; Ziemann, Ulf

    2011-06-01

    (1)H MRSI has evolved as an important tool to study the onset and progression of brain damage in multiple sclerosis. Abnormal increases in total creatine, total choline and myoinositol have been noted in multiple sclerosis. However, the pathobiochemical mechanisms related to these changes are still largely unclear. The combination of (1)H MRSI and (1)H-decoupled (31)P MRSI can specify to what extent phosphorylated components of total creatine and total choline contribute to this increase. Combined (1)H and (31)P MRSI data were obtained at 3 T in 22 patients with multiple sclerosis and in 23 healthy controls, and aligned with structural MRI to allow for correction for partial volume effects caused by cerebrospinal fluid and lesion load. A significant increase in total creatine was found in multiple sclerosis, and this was attributed to equal changes in the phosphorylated and unphosphorylated components. The concentrations of the putative glial markers total creatine and myoinositol in lesion-free (1)H MRSI voxels correlated with the global lesion load. We conclude that changes in total creatine are not related to altered energy metabolism, but rather indicate gliosis. Together with the increase in myoinositol, total creatine can be considered as a biomarker for disease severity. A significant total choline increase was mainly a result of choline components not visible by (31)P MRS. The origin of this residual choline fraction remains to be investigated. Copyright © 2010 John Wiley & Sons, Ltd.

  11. CombinePlt and CombineThs user manual: Merging multiple, processor-local plot and time-history data bases produced during a parallel calculation

    SciTech Connect

    Procassini, R.J.; DeGroot, A.J.

    1995-06-01

    The CombinePlt and CombineThs post-processing utilities are designed to merge the data in multiple, processor-local plot and time-history data bases produced by the parallel versions of the analysis codes DYNA3D, NIKE3D or PING into a serial data base which is compatible with the existing versions of the GRIZ and THUG visualization tools. These utilities make use of the partition assignment file produced by the PartMesh suite of pre-processing utilities to map the data from the processor-local order to global order. These utilities are also capable of translating 64-bit IEEE data bases into 32-bit IEEE data bases which are required for post-processing with GRIZ or THUG on an SGI workstation.

  12. 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

  13. Intraluminal thrombus thickness is not related to lower concentrations of trace elements in the wall of infrarenal abdominal aortic aneurysms.

    PubMed

    Ziaja, Damian; Kita, Andrzej; Janowska, Joanna; Pawlicki, Krzysztof; Mikuła, Barbara; Sznapka, Mariola; Chudek, Jerzy; Ziaja, Krzysztof

    2014-01-01

    Intraluminal thrombus (ILT) formation plays a significant role in the progression of infrarenal abdominal aortic aneurysms (AAA). Potentially, as ILT thickness increases the availability of trace elements in the aneurysm wall could decrease thereby leading to oxidative stress and intensifying pro-inflammatory cytokine generation. To determine if thrombus thickness is related to the concentration of trace elements in the wall of infrarenal AAA. The concentrations of trace elements in the wall of the aneurysm sack and ILT obtained from 19 consecutive patients during surgery for infrarenal AAA were determined using emission spectrometry. The concentrations of magnesium, zinc, manganese, and lead in the wall of AAA were significantly greater than in the ILT. Only the concentration of copper was lower in the AAA wall compared with the thrombus. The concentration of calcium, phosphorus, zinc, lead, copper, and magnesium increased with ILT thickness. The concentrations of no other trace elements in the wall of AAA were found to be related to the ILT thickness. Intraluminal thrombus thickness is not associated with a lower concentration of trace elements in the wall of the infrarenal AAA. Thus, the intraluminal thrombus participates in the progression of AAA by mechanisms independent of trace element supply to the wall of the aneurysm sack. Copyright © 2013 Elsevier GmbH. All rights reserved.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

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

    PubMed

    Anvari, B; Rastegar, S; Motamedi, M

    1994-09-01

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

  2. 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.

  3. 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.

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

    PubMed

    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

    2017-02-20

    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.

  5. Association of intraluminal thrombus, hemodynamic forces, and abdominal aortic aneurysm expansion using longitudinal CT images

    PubMed Central

    Zambrano, Byron A.; Gharahi, Hamidreza; Lim, ChaeYoung; Jaberi, Farhad A.; Choi, Jongeun; Lee, Whal; Baek, Seungik

    2016-01-01

    While hemodynamic forces and intraluminal thrombus (ILT) are believed to play important roles on abdominal aortic aneurysm (AAA), it has been suggested that hemodynamic forces and ILT also interact with each other, making it a complex problem. There is, however, a pressing need to understand relationships among three factors: hemodynamics, ILT accumulation, and AAA expansion for AAA prognosis. Hence this study used longitudinal CT scans from 14 patients and analyzed the relationship between them. Hemodynamic forces, represented by wall shear stress (WSS), were obtained from computational fluid dynamics; ILT accumulation was described by ILT thickness distribution changes between consecutives scans, and ILT accumulation and AAA expansion rates were estimated from changes in ILT and AAA volume. Results showed that, while low WSS was observed at regions where ILT accumulated, the rate at which ILT accumulated occurred at the same rate as the aneurysm expansion. Comparison between AAAs with and without thrombus showed that aneurysm with ILT recorded lower values of WSS and higher values of AAA expansion than those without thrombus. Findings suggest that low WSS may promote ILT accumulation and submit the idea that by increasing WSS levels ILT accumulation may be prevented. PMID:26429788

  6. A Computational Model of Biochemomechanical Effects of Intraluminal Thrombus on the Enlargement of Abdominal Aortic Aneurysms

    PubMed Central

    Humphrey, Jay D.; Karšaj, Igor

    2015-01-01

    Abdominal aortic aneurysms (AAAs) typically develop an intraluminal thrombus (ILT), yet most computational models of AAAs have focused on either the mechanics of the wall or the hemodynamics within the lesion, both in the absence of ILT. In the few cases wherein ILT has been modeled directly, as, for example, in static models that focus on the state of stress in the aortic wall and the associated rupture risk, thrombus has been modeled as an inert, homogeneous, load-bearing material. Given the biochemomechanical complexity of an ILT, there is a pressing need to consider its diverse effects on the evolving aneurysmal wall. Herein, we present the first growth and remodeling model that addresses together the biomechanics, mechanobiology, and biochemistry of thrombus-laden AAAs. Whereas it has been shown that aneurysmal enlargement in the absence of ILT depends primarily on the stiffness and turnover of fibrillar collagen, we show that the presence of a thrombus within lesions having otherwise the same initial wall composition and properties can lead to either arrest or rupture depending on the biochemical effects (e.g., release of proteases) and biomechanical properties (e.g., stiffness of fibrin) of the ILT. These computational results suggest that ILT should be accounted for when predicting the potential enlargement or rupture risk of AAAs and highlight specific needs for further experimental and computational research. PMID:26070724

  7. [Volume and function of the right ventricle before and after intraluminal pulmonary valvuloplasty].

    PubMed

    Rangel-Abundis, A; López, H; Badui, E; Martínez-Becerril, A

    1991-01-01

    With the purpose of studying the right ventricular infundibulum response to the obstruction of the pulmonary blood flow, the authors inform the results of the right ventricular volumes, and function changes before and after pulmonary intraluminal valvuloplasty performed in six adult patients with congenital stenosis of the pulmonary valve. After the valvuloplasty, all right ventricular volumes increased but only slightly, except for the end systolic volume at the right infundibulum, which decreased after valvuloplasty (for alpha = 0.10, p less than 0.10). The ejection fraction of this infundibulum increased after valvuloplasty (for alpha = 0.05 p less than 0.03), while the ejection fraction of the inflow chamber remained unaltered. In the same way decreased the work and power of the inflow tract of the right ventricle, regardless the decreased in the ventricular overload post-valvuloplasty; however, the ratio work vs. end diastolic volume of the right ventricle decreased (for alpha = 0.05, p less than 0.03). The authors discuss these results in relation with the changes produced by the obstruction, acute or chronic, of the pulmonary blood flow on the infundibular wall tension and contractility, whose structure and behavior allow to propose that the function of the infundibulum by means of contraction protects the pulmonary vasculature, against right ventricle hypertension.

  8. Impact of poroelasticity of intraluminal thrombus on wall stress of abdominal aortic aneurysms

    PubMed Central

    2012-01-01

    Background The predictions of stress fields in Abdominal Aortic Aneurysm (AAA) depend on constitutive descriptions of the aneurysm wall and the Intra-luminal Thrombus (ILT). ILT is a porous diluted structure (biphasic solid–fluid material) and its impact on AAA biomechanics is controversially discussed in the literature. Specifically, pressure measurements showed that the ILT cannot protect the wall from the arterial pressure, while other (numerical and experimental) studies showed that at the same time it reduces the stress in the wall. Method To explore this phenomenon further a poroelastic description of the ILT was integrated in Finite Element (FE) Models of the AAA. The AAA model was loaded by a pressure step and a cyclic pressure wave and their transition into wall tension was investigated. To this end ILT’s permeability was varied within a microstructurally motivated range. Results The two-phase model verified that the ILT transmits the entire mean arterial pressure to the wall while, at the same time, it significantly reduces the stress in the wall. The predicted mean stress in the AAA wall was insensitive to the permeability of the ILT and coincided with the results of AAA models using a single-phase ILT description. Conclusion At steady state, the biphasic ILT behaves like a single-phase material in an AAA model. Consequently, computational efficient FE single-phase models, as they have been exclusively used in the past, accurately predict the wall stress in AAA models. PMID:22931215

  9. Low-profile visible intraluminal support device: immediate outcome of the first three US cases.

    PubMed

    Turner, Raymond D; Turk, Aquilla; Chaudry, Imran

    2013-03-01

    Dissecting and wide-necked aneurysms that incorporate a large portion of the parent artery can be challenging to treat with currently available devices. This study reports three cases treated with a new hybrid stent design that incorporates a smaller cell size and more pliable design than current generation stents and results in some flow diversion characteristics. In all three cases, use of the low-profile visible intraluminal support (LVIS) device in conjunction with coil embolization was determined to provide the best opportunity to achieve aneurysm occlusion while mitigating adverse events. The institutional review board reviewed all cases and approval was obtained. All cases were performed under emergent use exemption from the US Food and Drug Administration. All three patients were successfully stent coiled with the LVIS device. One patient was completely occluded initially and remained so at follow-up, one patient progressed to complete occlusion at follow-up, and the last patient had stable incomplete occlusion of their fusiform aneurysm. There were no complications related to the procedures and the patients were maintained on dual-antiplatelet therapy. The LVIS device offers promise as a stent-assisted coil device with certain characteristics that may be advantageous over currently available microstents.

  10. [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.

  11. 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.

  12. 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-08-01

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

  16. 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...

  17. Occupational therapists prefer combining multiple intervention approaches for children with learning difficulties.

    PubMed

    Nelson, Alison; Copley, Jodie; Flanigan, Kerry; Underwood, Katherine

    2009-02-01

    Research to date has not fully explored how occupational therapists provide intervention for children with learning difficulties in their day-to-day practice. The purpose of this study was to provide an in-depth description of the approaches and techniques used and how they are applied and combined to meet the complex and multifaceted needs of these children. In-depth interviews and short questionnaires were completed by seven occupational therapists who had provided intervention to children with learning difficulties. Observations of therapy sessions were also conducted. Thematic analysis gained insight into the approaches and techniques therapists used and how these were applied in practice. Therapists use a wide range of approaches in various combinations because they feel that these best meet the needs of individual children. Sensory-based and cognitive approaches were most frequently drawn from and combined with other approaches such as visual information analysis, biomechanical and psychosocial approaches added for particular purposes. Approaches were usually combined simultaneously within an activity or session. Therapists create their own 'multimodel' approach in order to best meet the needs of their clients. They are able to articulate the theoretical basis behind these choices, although lack of clarity exists about the frames of reference being used.

  18. 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

  19. 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,…

  20. 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,…

  1. 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.

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. 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.

  5. 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.

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

    PubMed

    Verma, Shefali S; de Andrade, Mariza; Tromp, Gerard; Kuivaniemi, Helena; Pugh, Elizabeth; Namjou-Khales, Bahram; Mukherjee, Shubhabrata; Jarvik, Gail P; Kottyan, Leah C; Burt, Amber; Bradford, Yuki; Armstrong, Gretta D; Derr, Kimberly; Crawford, Dana C; Haines, Jonathan L; Li, Rongling; Crosslin, David; Ritchie, Marylyn D

    2014-01-01

    The electronic MEdical Records and GEnomics (eMERGE) network brings together DNA biobanks linked to electronic health records (EHRs) from multiple institutions. Approximately 51,000 DNA samples from distinct individuals have been genotyped using genome-wide SNP arrays across the nine sites of the network. The eMERGE Coordinating Center and the Genomics Workgroup developed a pipeline to impute and merge genomic data across the different SNP arrays to maximize sample size and power to detect associations with a variety of clinical endpoints. The 1000 Genomes cosmopolitan reference panel was used for imputation. Imputation results were evaluated using the following metrics: accuracy of imputation, allelic R (2) (estimated correlation between the imputed and true genotypes), and the relationship between allelic R (2) and minor allele frequency. Computation time and memory resources required by two different software packages (BEAGLE and IMPUTE2) were also evaluated. A number of challenges were encountered due to the complexity of using two different imputation software packages, multiple ancestral populations, and many different genotyping platforms. We present lessons learned and describe the pipeline implemented here to impute and merge genomic data sets. The eMERGE imputed dataset will serve as a valuable resource for discovery, leveraging the clinical data that can be mined from the EHR.

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

    PubMed Central

    Verma, Shefali S.; de Andrade, Mariza; Tromp, Gerard; Kuivaniemi, Helena; Pugh, Elizabeth; Namjou-Khales, Bahram; Mukherjee, Shubhabrata; Jarvik, Gail P.; Kottyan, Leah C.; Burt, Amber; Bradford, Yuki; Armstrong, Gretta D.; Derr, Kimberly; Crawford, Dana C.; Haines, Jonathan L.; Li, Rongling; Crosslin, David; Ritchie, Marylyn D.

    2014-01-01

    The electronic MEdical Records and GEnomics (eMERGE) network brings together DNA biobanks linked to electronic health records (EHRs) from multiple institutions. Approximately 51,000 DNA samples from distinct individuals have been genotyped using genome-wide SNP arrays across the nine sites of the network. The eMERGE Coordinating Center and the Genomics Workgroup developed a pipeline to impute and merge genomic data across the different SNP arrays to maximize sample size and power to detect associations with a variety of clinical endpoints. The 1000 Genomes cosmopolitan reference panel was used for imputation. Imputation results were evaluated using the following metrics: accuracy of imputation, allelic R2 (estimated correlation between the imputed and true genotypes), and the relationship between allelic R2 and minor allele frequency. Computation time and memory resources required by two different software packages (BEAGLE and IMPUTE2) were also evaluated. A number of challenges were encountered due to the complexity of using two different imputation software packages, multiple ancestral populations, and many different genotyping platforms. We present lessons learned and describe the pipeline implemented here to impute and merge genomic data sets. The eMERGE imputed dataset will serve as a valuable resource for discovery, leveraging the clinical data that can be mined from the EHR. PMID:25566314

  8. 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

  9. 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

  10. 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

  11. Combining model-based measurement results of critical dimensions from multiple tools

    NASA Astrophysics Data System (ADS)

    Zhang, Nien Fan; Barnes, Bryan M.; Zhou, Hui; Henn, Mark-Alexander; Silver, Richard M.

    2017-06-01

    Model-based measurement techniques use experimental data and simulations of the underlying physics to extract quantitative estimates of the measurands of a specimen based upon a parametric model of that specimen. The uncertainties of these estimates are based upon not only the uncertainties in the experimental data, but also the sensitivity of that data to the model parameters, and parametric correlations among those parameters. The combination of two or more model-based techniques as well as the Bayesian approach are shown to be optimal for obtaining the lowest possible uncertainties. As an example, using this form of hybrid metrology, state-of-the-art sub-14 nm wide lines from semiconductor manufacturing are measured using a combined regression from critical-dimension small-angle x-ray scattering and scanning electron microscopy that leads to lower uncertainties.

  12. 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

  13. 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.

  14. 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.

  15. Examining the benefits of combining two learning strategies on recall of functional information in persons with multiple sclerosis.

    PubMed

    Goverover, Yael; Basso, Michael; Wood, Hali; Chiaravalloti, Nancy; DeLuca, John

    2011-12-01

    Forgetfulness occurs commonly in people with multiple sclerosis (MS), but few treatments alleviate this problem. This study examined the combined effect of two cognitive rehabilitation strategies to improve learning and memory in MS: self-generation and spaced learning. The hypothesis was that the combination of spaced learning and self-generation would yield better learning and memory recall performance than spaced learning alone. Using a within groups design, 20 participants with MS and 18 healthy controls (HC) were presented with three tasks (learning names, appointment, and object location), each in three learning conditions (Massed, Spaced Learning, and combination of spaced and generated information). Participants were required to recall the information they learned in each of these conditions immediately and 30 min following the initial presentation. The combination of spaced learning and self-generation yielded better recall than did spaced learning alone. In turn, spaced learning resulted in better recall than the massed rehearsal condition. These findings reveal that the combination of these two learning strategies may possess utility as a cognitive rehabilitation strategy.

  16. [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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Multiple-band perfect absorbers based on the combination of Fabry-Perot resonance and the gap plasmon resonance

    NASA Astrophysics Data System (ADS)

    Zhai, Yusheng; Chen, Guangdian; Xu, Ji; Qi, Zhiyang; Li, Xiaohua; Wang, Qilong

    2017-09-01

    To realize multiple-band perfect absorption, a novel nanostructure consisting of subwavelength periodic metallic grating and a thick metallic substrate, separated by a thin dielectric spacer(MGDM), is proposed in this paper. Compared with the structures without the dielectric spacer, the designed MGDM nanostructure not only possesses the absorption peaks caused by the Fabry-Perot resonance in the grating slits, but also possesses additional absorption peaks. Numerical simulation results show that the additional absorption peaks are caused by the gap plasmon resonance in the dielectric spacer. Besides, the influence of structural parameters on the absorption properties of MGDM are also thoroughly investigated. The combination of Fabry-Perot resonance and the gap plasmon resonance in the proposed MGDM provide another route for designing multiple-band perfect absorber nanostructures, which have an extensive applications in photo-detecting, photo-conversion or photo-harvesting.

  2. How similar are commonly combined criteria for EDSS progression in multiple sclerosis?

    PubMed

    Kragt, J J; Nielsen, I M; van der Linden, F A H; Uitdehaag, B M J; Polman, C H

    2006-12-01

    Measuring disease progression is an important aspect of multiple sclerosis (MS) clinical trials. Commonly applied disability endpoints include time to clinically meaningful Expanded Disability Status Scale (EDSS) change, or the number of patients in whom such a change has occurred. Typically, clinically meaningful EDSS change has been defined as a change of 1.0 point on Kurtzke's EDSS in patients with an entry EDSS score of 5.5 or lower, or 0.5 point in patients with a higher EDSS score. Our goal was to evaluate whether these changes can be considered as similar. Therefore, we compared EDSS changes to corresponding changes in the Guy's Neurological Disability Scale (GNDS), which is a measure of patient perceived disability, and the Multiple Sclerosis Functional Composite (MSFC), which is an examination-based quantitative scoring of neurological impairment. From a large longitudinal database, we selected two groups of patients with a clinically meaningful change in EDSS score according to the usual criteria: patients with EDSS change > or = 1.0 for baseline EDSS < or = 5.5 and patients with EDSS change > or = 0.5 for baseline EDSS > or = 6.0. We compared changes in GNDS sum score and in MSFC score between both groups. In the group with baseline EDSS > or = 6.0, GNDS and MSFC changes were higher than in patients with baseline EDSS < or = 5.5. The difference in change was 1.00 (95% confidence interval (CI): -0.35 to 2.36) for the GNDS and 0.412 (95% CI: 0.300-0.525) for the MSFC. Our results indicate that a 0.5 point EDSS change in patients with baseline EDSS > or = 6.0 cannot be considered equal to a 1.0 point change in patients with baseline EDSS < or = 5.5.

  3. Combining Transcriptome Assemblies from Multiple De Novo Assemblers in the Allo-Tetraploid Plant Nicotiana benthamiana

    PubMed Central

    Nakasugi, Kenlee; Crowhurst, Ross; Bally, Julia; Waterhouse, Peter

    2014-01-01

    Background Nicotiana benthamiana is an allo-tetraploid plant, which can be challenging for de novo transcriptome assemblies due to homeologous and duplicated gene copies. Transcripts generated from such genes can be distinct yet highly similar in sequence, with markedly differing expression levels. This can lead to unassembled, partially assembled or mis-assembled contigs. Due to the different properties of de novo assemblers, no one assembler with any one given parameter space can re-assemble all possible transcripts from a transcriptome. Results In an effort to maximise the diversity and completeness of de novo assembled transcripts, we utilised four de novo transcriptome assemblers, TransAbyss, Trinity, SOAPdenovo-Trans, and Oases, using a range of k-mer sizes and different input RNA-seq read counts. We complemented the parameter space biologically by using RNA from 10 plant tissues. We then combined the output of all assemblies into a large super-set of sequences. Using a method from the EvidentialGene pipeline, the combined assembly was reduced from 9.9 million de novo assembled transcripts to about 235,000 of which about 50,000 were classified as primary. Metrics such as average bit-scores, feature response curves and the ability to distinguish paralogous or homeologous transcripts, indicated that the EvidentialGene processed assembly was of high quality. Of 35 RNA silencing gene transcripts, 34 were identified as assembled to full length, whereas in a previous assembly using only one assembler, 9 of these were partially assembled. Conclusions To achieve a high quality transcriptome, it is advantageous to implement and combine the output from as many different de novo assemblers as possible. We have in essence taking the ‘best’ output from each assembler while minimising sequence redundancy. We have also shown that simultaneous assessment of a variety of metrics, not just focused on contig length, is necessary to gauge the quality of assemblies. PMID

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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).

  9. 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.

  10. Individual and Combined Effects of Multiple High-Risk Triggers on Postcessation Smoking Urge and Lapse

    PubMed Central

    2014-01-01

    Introduction: Negative affect, alcohol consumption, and presence of others smoking have consistently been implicated as risk factors for smoking lapse and relapse. What is not known, however, is how these factors work together to affect smoking outcomes. This paper uses ecological momentary assessment (EMA) collected during the first 7 days of a smoking cessation attempt to test the individual and combined effects of high-risk triggers on smoking urge and lapse. Methods: Participants were 300 female smokers who enrolled in a study that tested an individually tailored smoking cessation treatment. Participants completed EMA, which recorded negative affect, alcohol consumption, presence of others smoking, smoking urge, and smoking lapse, for 7 days starting on their quit date. Results: Alcohol consumption, presence of others smoking, and negative affect were, independently and in combination, associated with increase in smoking urge and lapse. The results also found that the relationship between presence of others smoking and lapse and the relationship between negative affect and lapse were moderated by smoking urge. Conclusions: The current study found significant individual effects of alcohol consumption, presence of other smoking, and negative affect on smoking urge and lapse. Combing the triggers increased smoking urge and the risk for lapse to varying degrees, and the presence of all 3 triggers resulted in the highest urge and lapse risk. PMID:24323569

  11. 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.

  12. 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

  13. Characterization of intraluminal impedance patterns associated with gas reflux in healthy volunteers.

    PubMed

    van Wijk, M P; Sifrim, D; Rommel, N; Benninga, M A; Davidson, G P; Omari, T I

    2009-08-01

    Multichannel intraluminal impedance (MII) recording allows assessment of flow through the oesophagus and differentiation between liquid and gas contents. Existing MII criteria for recognition of gas gastro-oesophageal reflux (GOR) have not been validated during known gas GOR in humans. (i) Characterize MII patterns of known gas GOR and optimize criteria. (ii) Clarify interrelationships between magnitude of maximal impedance change, luminal diameter and electrode-mucosa contact. Ten healthy volunteers (six male, 21-37 years) were studied using an oesophageal MII-manometry catheter. After catheter placement, subjects were asked to drink 600 mL of carbonated soft drink. Recordings were made for 20 min and the protocol repeated. Reported belches confirmed manometrically (triggered by transient lower oesophageal sphincter relaxations) were included for analysis. Those episodes were compared against commonly used criteria. Another five subjects (three male, 26-52 years) underwent simultaneous MII and videofluoroscopy using the same protocol. Videofluoroscopic images were analyzed for luminal diameter and the presence of electrode-mucosa contact. All analyzed gas GOR episodes (n = 88) were associated with a pattern of impedance rise which was either retrograde (62.5%), synchronous (19.3%) or antegrade (18.2%). Depending on the exact criteria used, sensitivity ranged from 33% to 75%. A multivariate regression model including luminal diameter and the presence of electrode-mucosa contact as independent factors accounted for 53% of all variation in impedance changes. In conclusion, a significant number of gas GOR episodes does not meet criteria for their recognition. New criteria are proposed to include specific antegrade patterns of impedance rise. Luminal diameter and the extent of contact between the oesophageal mucosa and MII-electrodes influence the magnitude and patterning of impedance change.

  14. Can acid (pH) refluxes predict multichannel intraluminal impedance refluxes? A correlation study.

    PubMed

    Misra, Sudipta

    2010-04-01

    The present study aims to explore if and when acid (pH) refluxes can predict refluxes detected by multichannel intraluminal impedance (MII) studies. This correlation may indicate whether pH probe-only and MII-pH studies are interchangeable. Prospective observational cross sectional study of symptomatic children (below 18 years) who had MII-pH studies done for gastroesophageal reflux. Clinical data were extracted from patient records. Non-parametric tests, Pearson's rho and receiver operating characteristic (ROC) curves were used for data analysis. A total of 153 children were included in the study and 62% were on acid suppression. Indices for acid and MII refluxes correlated with each other only in those without acid suppression. This correlation was lost in children on acid suppression. There was no statistically significant difference in acid or MII reflux indices in children with or without acid suppression. Like acid reflux, indices for MII refluxes had good correlation with each other irrespective of acid suppression. Liquid and mixed MII refluxes showed excellent correlation with respective types of proximally migrating refluxes. The values for MII reflux indices derived from our patient population were in broad agreement with available pediatric and adult data. A pH probe-only study in patients without acid suppression may reflect both acid and volume (MII) reflux activities adequately and can substitute for MII-pH study. The observed excellent correlation between acid and MII refluxes with proximal migration may justify using pH probe-only studies for extra esophageal symptoms in patients without acid suppression.

  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. Phantom system for intraluminal x-ray imaging of the human colon

    NASA Astrophysics Data System (ADS)

    Lifshitz, Ronen; Nawi-Srur, Sivan; Katz, Batia; Milman, Lena; Gubich, Dmitry; Lewkowicz, Shlomo; Kimchy, Yoav

    2017-03-01

    The Check-Cap capsule, C-Scan Cap, performs intraluminal imaging of the human colon based on X-Ray scatter processes. Basic performance of such a system can be demonstrated using various tube-like phantom objects. Also, from a perspective of capsule dynamics, actuators can and have been used for capsule manipulation. Nevertheless the actual situation of a capsule in use is extremely complex, both in terms of the imaging-target object itself and the capsule dynamics within the same. In order to allow study of imaging system performance in a pseudo-clinical environment, a specialized phantom system has been developed. A tissue-equivalent material has been developed in-house, so as to allow simple usage and flexibility for making a wide variety of phantoms, simple tubes as well as extremely complex segments of the human colon which can possibly demonstrate adenomas. The material itself is durable, flexible, and very similar to water in terms of X-Ray scattering. Based on real abdominal CT images, real colon segments have been extracted to become 3D molds, which were used for producing a set of pseudo-clinical human colon segments. In the aspect of capsule and colon dynamics, capsule propulsion within these phantoms is based on the contents, i.e. capsule is hydro-dynamically propelled by surrounding medium rather than actuators. In addition, a system for generating peristaltic contractions along these colon segments has been developed; this system allows stimulation of the colon and the capsule within using arbitrary programmable contraction waves. This phantom system allows demonstration of pseudoclinical imaging scenarios in the lab.

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

    PubMed Central

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

    2014-01-01

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

  18. Intraluminal pressure stimulates MAPK phosphorylation in arterioles: temporal dissociation from myogenic contractile response.

    PubMed

    Spurrell, Brian E; Murphy, Timothy V; Hill, Michael A

    2003-10-01

    Members of the MAPK family of enzymes, p42/44 and p38, have been implicated in both the regulation of contractile function and growth responses in vascular smooth muscle. We determined whether such kinases are activated during the arteriolar myogenic response after increases in intraluminal pressure. Particular emphasis was placed on temporal aspects of activation to determine whether such phosphorylation events parallel the known time course for myogenic contraction. Experiments used single cannulated arterioles isolated from the cremaster muscle of rats with some vessels loaded with the fluorescent Ca2+-sensitive dye fura 2 (2 microM). The p42/44 inhibitor PD-98059 (50 microM) caused vasodilation but did not prevent pressure-induced myogenic constriction. The vasodilator response was accompanied by decreased smooth muscle intracellular Ca2+. Western blotting revealed a significant increase in the level of phosphorylation of p42/44 15 min after the application of a 30- to 100-mmHg pressure step. Phosphorylation of p42/44 was a late event that appeared to be temporally dissociated from contraction, which was complete within 1-5 min. EGF (80 nM) caused marked phosphorylation of p42/44 but only acted as a weak vasoconstrictor. The p38 inhibitor SB-203580 (10 microM) did not alter baseline diameter, nor did it prevent myogenic vasoconstriction. Consistent with these observations, SB-203580 did not cause a measurable change in intracellular Ca2+. The results demonstrate activation of the p42/44 class of MAPK resulting from increased transmural pressure. Such activation is, however, dissociated from the acute pressure-induced vasoconstrictor response in terms of time course and may represent the activation of compensatory, but parallel, pathways, including those related to growth and remodeling.

  19. Efficacy of Two Combinations of Blood Purification Techniques for the Treatment of Multiple Organ Failure Induced by Wasp Stings.

    PubMed

    Yuan, Hai; Chen, Shuangqin; Hu, Fengqi; Zhang, Qi

    2016-01-01

    The aim of this study was to explore the clinical efficacy of 2 combinations of blood purification techniques in patients with sting venom-induced multiple organ dysfunction syndrome (MODS). A total of 23 patients received 35 sessions of hemoperfusion (HP) + continuous veno-venous hemodiafiltration (CVVHDF) treatment and 22 sessions of plasma exchange (PE) + CVVHDF treatment, respectively. Both HP + CVVHDF and PE + CVVHDF reduced the levels of inflammation, thus improving our patients' health condition. Moreover, PE + CVVHDF was found to be significantly more effective in reducing the levels of specific liver function markers and inflammatory mediators, as well as shortening prothrombin time and increasing the levels of serum albumin. Both combinations of blood purification techniques were capable of improving MODS. However, the PE + CVVHDF approach was more efficient for the removal of wasp venom and inflammatory mediators from the blood. © 2016 S. Karger AG, Basel.

  20. 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

  1. 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.

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

    PubMed Central

    Sexton, Ken

    2012-01-01

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

  3. 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.

  4. Comparative proteogenomics: Combining mass spectrometry and comparative genomics to analyze multiple genomes

    PubMed Central

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

    2008-01-01

    Recent proliferation of low-cost DNA sequencing techniques will soon lead to an explosive growth in the number of sequenced genomes and will turn manual annotations into a luxury. Mass spectrometry recently emerged as a valuable technique for proteogenomic annotations that improves on the state-of-the-art in predicting genes and other features. However, previous proteogenomic approaches were limited to a single genome and did not take advantage of analyzing mass spectrometry data from multiple genomes at once. We show that such a comparative proteogenomics approach (like comparative genomics) allows one to address the problems that remained beyond the reach of the traditional “single proteome” approach in mass spectrometry. In particular, we show how comparative proteogenomics addresses the notoriously difficult problem of “one-hit-wonders” in proteomics, improves on the existing gene prediction tools in genomics, and allows identification of rare post-translational modifications. We therefore argue that complementing DNA sequencing projects by comparative proteogenomics projects can be a viable approach to improve both genomic and proteomic annotations. PMID:18426904

  5. 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.

  6. Meta-Analysis of Untargeted Metabolomic Data: Combining Results from Multiple Profiling Experiments

    PubMed Central

    Patti, Gary J.; Tautenhahn, Ralf; Siuzdak, Gary

    2013-01-01

    metaXCMS is a software program for the analysis of liquid chromatography/mass spectrometry-based untargeted metabolomic data that is designed to identify differences in metabolic profiles across multiple sample groups (e.g., “healthy” versus “active disease” versus “inactive disease”). By performing second-order (“meta”) analysis, the software facilitates prioritization of interesting metabolite features from large untargeted metabolomic datasets prior to the rate-limiting step of structural identification. Here we provide a detailed step-by-step protocol for going from raw mass spectrometry data to metaXCMS results visualized as Venn diagrams and exported Microsoft Excel spreadsheets. There is no upper limit to the number of sample groups or individual samples that can be compared by the software, and data from most commercial mass spectrometers is supported. The speed of the analysis depends on computational resources and data volume, but will generally be less than one day for most users. metaXCMS is freely available at http://metlin.scripps.edu/metaXCMS/. PMID:22343432

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

    PubMed

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

    2013-08-30

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

  8. 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

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

    PubMed

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

    2008-07-01

    Recent proliferation of low-cost DNA sequencing techniques will soon lead to an explosive growth in the number of sequenced genomes and will turn manual annotations into a luxury. Mass spectrometry recently emerged as a valuable technique for proteogenomic annotations that improves on the state-of-the-art in predicting genes and other features. However, previous proteogenomic approaches were limited to a single genome and did not take advantage of analyzing mass spectrometry data from multiple genomes at once. We show that such a comparative proteogenomics approach (like comparative genomics) allows one to address the problems that remained beyond the reach of the traditional "single proteome" approach in mass spectrometry. In particular, we show how comparative proteogenomics addresses the notoriously difficult problem of "one-hit-wonders" in proteomics, improves on the existing gene prediction tools in genomics, and allows identification of rare post-translational modifications. We therefore argue that complementing DNA sequencing projects by comparative proteogenomics projects can be a viable approach to improve both genomic and proteomic annotations.

  10. 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.

  11. 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.

  12. 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.

  13. Variable-length lapped transforms with a combination of multiple synthesis filter banks for image coding.

    PubMed

    Tanaka, Toshihisa; Hirasawa, Yasutaka; Yamashita, Yukihiko

    2006-01-01

    A class of lapped transforms for image coding, which are characterized by variable-length synthesis filters, is introduced. In this class, the synthesis filter bank (FB) is first defined with an arbitrary combination of finite impulse response synthesis filters of perfect reconstruction FBs. An analysis FB is then obtained using direct matrix inversion or iterative implementation of Neumann series expansion. Moreover, to improve compression, we introduce a unitary transform that follows the analysis FB. This class enables a greater freedom of design than previously presented variable-length lapped transforms. We illustrate several design examples and present experimental results for image coding, which indicate that the proposed transforms are promising and comparable with conventional subband transforms including wavelets.

  14. A phase I study of samarium lexidronam/bortezomib combination therapy for the treatment of relapsed or refractory multiple myeloma.

    PubMed

    Berenson, James R; Yellin, Ori; Patel, Ravi; Duvivier, Herb; Nassir, Youram; Mapes, Russell; Abaya, Christina DiLauro; Swift, Regina A

    2009-02-01

    This open-label, phase I dose-escalation study assessed the safety, tolerability, and initial efficacy of Samariam 153 (153Sm)-lexidronam/bortezomib combination therapy for patients with relapsed/refractory multiple myeloma. Patients were enrolled in six cohorts and given bortezomib (1.0 or 1.3 mg/m2) on days 1, 4, 8, and 11 and 153Sm-lexidronam (0.25, 0.5, or 1.0 mCi/kg) on day 3 of a 56-day cycle (maximum of four cycles). The primary endpoints were safety and tolerability of the 153Sm-lexidronam/bortezomib regimen. Twenty-four patients were enrolled. Median values for age, time since diagnosis, and number of prior treatments were 63 years, 29 months, and three regimens, respectively. The most common toxicities were hematologic; during the first cycle, median neutrophil and platelet nadirs were 1,000/mm3 and 98,500/mm3, respectively, and observed generally 3 to 4 weeks post-treatment. The incidences of grade 4 neutropenia and thrombocytopenia were 12.5% and 8.3%, respectively, during treatment cycle 1. Dose-limiting toxicity, reached in cohort 6 as a result of hematologic toxicity, defined the maximum tolerated dose as 0.5 mCi/kg 153Sm-lexidronam in combination with 1.3 mg/m2 bortezomib. The maximum tolerated dose for 153Sm-lexidronam in combination with the 1.0 mg/m2 bortezomib was not reached. No nonhematologic dose-limiting toxicities were observed; both the incidence and the severity of peripheral neuropathy were low. Responses occurred in 5 (21%) patients, including 3 (12.5%) complete and 2 (8.3%) minimal responses. Bortezomib combined with 153Sm-lexidronam appears to be a well-tolerated regimen, which showed clinical activity in this phase I trial for patients with relapsed or refractory multiple myeloma.

  15. 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. © 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  16. Error in geometric morphometric data collection: Combining data from multiple sources.

    PubMed

    Robinson, Chris; Terhune, Claire E

    2017-09-01

    This study compares two- and three-dimensional morphometric data to determine the extent to which intra- and interobserver and intermethod error influence the outcomes of statistical analyses. Data were collected five times for each method and observer on 14 anthropoid crania using calipers, a MicroScribe, and 3D models created from NextEngine and microCT scans. ANOVA models were used to examine variance in the linear data at the level of genus, species, specimen, observer, method, and trial. Three-dimensional data were analyzed using geometric morphometric methods; principal components analysis was employed to examine how trials of all specimens were distributed in morphospace and Procrustes distances among trials were calculated and used to generate UPGMA trees to explore whether all trials of the same individual grouped together regardless of observer or method. Most variance in the linear data was at the genus level, with greater variance at the observer than method levels. In the 3D data, interobserver and intermethod error were similar to intraspecific distances among Callicebus cupreus individuals, with interobserver error being higher than intermethod error. Generally, taxa separate well in morphospace, with different trials of the same specimen typically grouping together. However, trials of individuals in the same species overlapped substantially with one another. Researchers should be cautious when compiling data from multiple methods and/or observers, especially if analyses are focused on intraspecific variation or closely related species, as in these cases, patterns among individuals may be obscured by interobserver and intermethod error. Conducting interobserver and intermethod reliability assessments prior to the collection of data is recommended. © 2017 Wiley Periodicals, Inc.

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

    PubMed

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

    2016-04-01

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

  18. 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.

  19. 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.

  20. 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/. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed Central

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

    2015-01-01

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

  2. 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.

  3. The combined SOHO-STEREO dataset: Simultaneous observations of comets from multiple vantage points

    NASA Astrophysics Data System (ADS)

    Knight, M.; Begun, J.; Kelley, M.; Battams, K.; A'Hearn, M.

    2014-07-01

    The set of comets observed by Solar and Heliospheric Observatory (SOHO) and Solar-TErrestrial RElations Observatory (STEREO) provides a large (>2500 comets) and unique database for studying cometary properties. Sungrazing comets are discovered in SOHO or STEREO images on average every few days, with individual comets typically observable for up to a few days. We compiled photometry of more than 20 comets observed simultaneously by the same telescope and filter on both STEREO spacecraft to construct the first dust scattering phase function ever directly computed from simultaneous observations of the same object from two vantage points, thus removing uncertainty caused by changing heliocentric distance between observations. The collective dust scattering phase function spans phase angles from 28--153 deg and agrees reasonably well with the theoretical curve from [1]. However, individual comets deviate from the predicted curve by varying amounts during their apparition. This may suggest that the dust properties of individual comets change on the timescale of hours due to the dramatically different heliocentric distance or that the number of dust grains in the coma is changing due to nucleus activity, rotation, and/or erosion. We have also begun a study of the dust tails of selected well-observed comets in our database. This project utilizes the 3-D aspects of the combined SOHO and STEREO dataset to constrain the dust properties and time of release better than is possible with observations from a single location. We will present ongoing results of these investigations and place them into the wider context of sungrazing comet studies, notably by comparison with SOHO and STEREO observations of comet C/2012 S1 ISON [2], the most extensively observed sungrazing comet in history.

  4. 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.

  5. Combining electrophoresis with detection under ultraviolet light and multiple ultrafiltration for isolation of humic fluorescence fractions.

    PubMed

    Trubetskaya, Olga E; Shaloiko, Lubov A; Demin, Dmitrii V; Marchenkov, Victor V; Proskuryakov, Ivan I; Coelho, Christian; Trubetskoj, Oleg A

    2011-04-01

    Polyacrylamide gel electrophoresis of chernozem soil humic acids (HAs) followed by observation under UV (312 nm) excitation light reveals new low molecular weight (MW) fluorescent fractions. Ultrafiltration of HAs sample in 7 M urea on a membrane of low nominal MW retention (NMWR, 5 kDa) was repetitively used for separation of fluorescent and non-fluorescent species. Thirty ultrafiltrates and the final retentate R were obtained. Fluorescence maxima of separate ultrafiltrates were different and non-monotonously changed in the range of 475-505 nm. Fluorescence maxima of less than 490 nm were detected only in the four first utrafiltrates. For further physical-chemical analyses all utrafiltrates were combined into a fraction called UF<5 (NMW<5 kDa). Retentate R demonstrated very weak fluorescence under 270 nm excitation, while fluorescence intensity of UF<5 was about six times higher than of the bulk HAs. Fraction UF<5 was further ultrafiltrated on membranes of MNWR 3 kDa and 1 kDa, yielding three subfractions UF3-5, UF1-3 and UF<1 with NMW 3-5 kDa, 1-3 kDa and <1 kDa, respectively. The validation of the UF procedure was performed by size exclusion chromatography on Sephadex G-25 column. The fluorescence maxima were found to be at 505, 488 and 465 nm for UF3-5, UF1-3 and UF<1, respectively, with increasing of fluorescence intensity from UF3-5 to UF1-3 to UF<1 fraction. EPR analysis showed that the amount of free radicals was the largest in retentate R and drastically decreased in fluorescent ultrafiltrates. The results demonstrate that more than one fluorophore is present in chernozem soil HAs complex. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. 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.

  7. 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

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

    PubMed

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

    2016-11-21

    To evaluate the agreement of multichannel intraluminal impedance-pH monitoring (MII-pHM) and gastroesophageal reflux scintigraphy (GES) for the diagnosis of gastroesophageal reflux disease. 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. 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; 73.3%/0.116 and 60

  9. 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

  10. 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.

  11. [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.

  12. Reduce Manual Curation by Combining Gene Predictions from Multiple Annotation Engines, a Case Study of Start Codon Prediction

    PubMed Central

    Ederveen, Thomas H. A.; Overmars, Lex; van Hijum, Sacha A. F. T.

    2013-01-01

    Nowadays, prokaryotic genomes are sequenced faster than the capacity to manually curate gene annotations. Automated genome annotation engines provide users a straight-forward and complete solution for predicting ORF coordinates and function. For many labs, the use of AGEs is therefore essential to decrease the time necessary for annotating a given prokaryotic genome. However, it is not uncommon for AGEs to provide different and sometimes conflicting predictions. Combining multiple AGEs might allow for more accurate predictions. Here we analyzed the ab initio open reading frame (ORF) calling performance of different AGEs based on curated genome annotations of eight strains from different bacterial species with GC% ranging from 35–52%. We present a case study which demonstrates a novel way of comparative genome annotation, using combinations of AGEs in a pre-defined order (or path) to predict ORF start codons. The order of AGE combinations is from high to low specificity, where the specificity is based on the eight genome annotations. For each AGE combination we are able to derive a so-called projected confidence value, which is the average specificity of ORF start codon prediction based on the eight genomes. The projected confidence enables estimating likeliness of a correct prediction for a particular ORF start codon by a particular AGE combination, pinpointing ORFs notoriously difficult to predict start codons. We correctly predict start codons for 90.5±4.8% of the genes in a genome (based on the eight genomes) with an accuracy of 81.1±7.6%. Our consensus-path methodology allows a marked improvement over majority voting (9.7±4.4%) and with an optimal path ORF start prediction sensitivity is gained while maintaining a high specificity. PMID:23675487

  13. 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.

  14. Prognostic Validation of SKY92 and Its Combination With ISS in an Independent Cohort of Patients With Multiple Myeloma.

    PubMed

    van Beers, Erik H; van Vliet, Martin H; Kuiper, Rowan; de Best, Leonie; Anderson, Kenneth C; Chari, Ajai; Jagannath, Sundar; Jakubowiak, Andrzej; Kumar, Shaji K; Levy, Joan B; Auclair, Daniel; Lonial, Sagar; Reece, Donna; Richardson, Paul; Siegel, David S; Stewart, A Keith; Trudel, Suzanne; Vij, Ravi; Zimmerman, Todd M; Fonseca, Rafael

    2017-09-01

    High risk and low risk multiple myeloma patients follow a very different clinical course as reflected in their PFS and OS. To be clinically useful, methodologies used to identify high and low risk disease must be validated in representative independent clinical data and available so that patients can be managed appropriately. A recent analysis has indicated that SKY92 combined with the International Staging System (ISS) identifies patients with different risk disease with high sensitivity. Here we computed the performance of eight gene expression based classifiers SKY92, UAMS70, UAMS80, IFM15, Proliferation Index, Centrosome Index, Cancer Testis Antigen and HM19 as well as the combination of SKY92/ISS in an independent cohort of 91 newly diagnosed MM patients. The classifiers identified between 9%-21% of patients as high risk, with hazard ratios (HRs) between 1.9 and 8.2. Among the eight signatures, SKY92 identified the largest proportion of patients (21%) also with the highest HR (8.2). Our analysis also validated the combination SKY92/ISS for identification of three classes; low risk (42%), intermediate risk (37%) and high risk (21%). Between low risk and high risk classes the HR is >10. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. 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

  16. Fluid displacement from intraluminal thrombus of abdominal aortic aneurysm as a result of uniform compression.

    PubMed

    van Noort, Kim; Schuurmann, Richte Cl; Wermelink, Bryan; Slump, Cornelis H; Kuijpers, Karel C; de Vries, Jean-Paul Pm

    2017-01-01

    Objectives The results after aneurysm repair with an endovascular aneurysm sealing (EVAS) system are dependent on the stability of the aneurysm sac and particularly the intraluminal abdominal aortic thrombus (ILT). The postprocedural ILT volume is decreased compared with preprocedural ILT volume in aortic aneurysm patients treated with EVAS. We hypothesize that ILT is not stable in all patients and pressurization of the ILT may result in displacement of fluids from the ILT, no differently than serum is displaced from whole blood when it settles. To date, the mechanism and quantification of fluid displacement from ILT are unknown. Methods The study included 21 patients who underwent elective open abdominal aortic aneurysm repair. The ILT was harvested as a routine procedure during the operation. After excision of a histologic sample of the ILT specimen in four patients, ILT volume was measured and the ILT was compressed in a dedicated compression setup designed to apply uniform compression of 200 mmHg for 5 min. After compression, the volumes of the remaining thrombus and the displaced fluid were measured. Results The median (interquartile-range) of ILT volume before compression was 60 (66) mL, and a median of 5.7 (8.4) mL of fluid was displaced from the ILT after compression, resulting in a median thrombus volume decrease of 11% (10%). Fluid components can be up to 31% of the entire ILT volume. Histologic examination of four ILT specimens showed a reduction of the medial layer of the ILT after compression, which was the result of compression of fluid-containing canaliculi. Conclusions Applying pressure of 200 mmHg to abdominal aortic aneurysm ILT resulted in the displacement of fluid, with a large variation among patients. Fluid displacement may result in decrease of ILT volume during and after EVAS, which might have implications on pre-EVAS volume planning and on stability of the endobags during follow-up which may lead to migration, endoleak or both.

  17. 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

  18. Human Factors Evaluation of the XM30 Guided Multiple Launch Rocket System (GMLRS) in the Combined High Mobility Artillery Rocket System (HIMARS)-GMLRS Initial Operational Test

    DTIC Science & Technology

    2007-05-01

    a) Four guided MLRS rocket rods (24 rockets ), (b) one Army tactical missile system, (c) two M26 rocket pods (12 rockets ), and (d) one M26A2...Human Factors Evaluation of the XM30 Guided Multiple Launch Rocket System (GMLRS) in the Combined High Mobility Artillery Rocket System...Factors Evaluation of the XM30 Guided Multiple Launch Rocket System (GMLRS) in the Combined High Mobility Artillery Rocket System (HIMARS)-GMLRS

  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, 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 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. 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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...

  3. 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 using...

  4. 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

  5. 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.

  6. Onsager-Machlup action-based path sampling and its combination with replica exchange for diffusive and multiple pathways.

    PubMed

    Fujisaki, Hiroshi; Shiga, Motoyuki; Kidera, Akinori

    2010-04-07

    For sampling multiple pathways in a rugged energy landscape, we propose a novel action-based path sampling method using the Onsager-Machlup action functional. Inspired by the Fourier-path integral simulation of a quantum mechanical system, a path in Cartesian space is transformed into that in Fourier space, and an overdamped Langevin equation is derived for the Fourier components to achieve a canonical ensemble of the path at a finite temperature. To avoid "path trapping" around an initially guessed path, the path sampling method is further combined with a powerful sampling technique, the replica exchange method. The principle and algorithm of our method is numerically demonstrated for a model two-dimensional system with a bifurcated potential landscape. The results are compared with those of conventional transition path sampling and the equilibrium theory, and the error due to path discretization is also discussed.

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

    PubMed

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

    2016-08-01

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

  8. 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.

  9. 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.

  10. Intraluminal measurement of papillary duct urine pH, in vivo: a pilot study in the swine kidney.

    PubMed

    Handa, Rajash K; Lingeman, James E; Bledsoe, Sharon B; Evan, Andrew P; Connors, Bret A; Johnson, Cynthia D

    2016-06-01

    We describe the in vivo use of an optic-chemo microsensor to measure intraluminal papillary duct urine pH in a large mammal. Fiber-optic pH microsensors have a tip diameter of 140-µm that allows insertion into papillary Bellini ducts to measure tubule urine proton concentration. Anesthetized adult pigs underwent percutaneous nephrolithotomy to access the lower pole of the urinary collecting system. A flexible nephroscope was advanced towards an upper pole papilla with the fiber-optic microsensor contained within the working channel. The microsensor was then carefully inserted into Bellini ducts to measure tubule urine pH in real time. We successfully recorded tubule urine pH values in five papillary ducts from three pigs (1 farm pig and 2 metabolic syndrome Ossabaw pigs). Our results demonstrate that optical microsensor technology can be used to measure intraluminal urine pH in real time in a living large mammal. This opens the possibility for application of this optical pH sensing technology in nephrolithiasis.

  11. TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10min or shorter.

    PubMed

    Durukan Tolvanen, A; Tatlisumak, E; Pedrono, E; Abo-Ramadan, U; Tatlisumak, T

    2017-05-15

    Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30min, n=6-8pergroup) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10min of ischemia followed up to 1week after reperfusion remained free of infarction and any MRI signal change. Thus, 10min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. 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

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

    PubMed

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

    2014-09-17

    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.

  14. 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

  15. 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

  16. Concurrent combined verification: reducing false positives in automated NMR structure verification through the evaluation of multiple challenge control structures.

    PubMed

    Golotvin, Sergey S; Pol, Rostislav; Sasaki, Ryan R; Nikitina, Asya; Keyes, Philip

    2012-06-01

    Automated structure verification using (1)H NMR data or a combination of (1)H and heteronuclear single-quantum correlation (HSQC) data is gaining more interest as a routine application for qualitative evaluation of large compound libraries produced by synthetic chemistry. The goal of this automated software method is to identify a manageable subset of compounds and data that require human review. In practice, the automated method will flag structure and data combinations that exhibit some inconsistency (i.e. strange chemical shifts, conflicts in multiplicity, or overestimated and underestimated integration values) and validate those that appear consistent. One drawback of this approach is that no automated system can guarantee that all passing structures are indeed correct structures. The major reason for this is that approaches using only (1)H or even (1)H and HSQC spectra often do not provide sufficient information to properly distinguish between similar structures. Therefore, current implementations of automated structure verification systems allow, in principle, false positive results. Presented in this work is a method that greatly reduces the probability of an automated validation system passing incorrect structures (i.e. false positives). This novel method was applied to automatically validate 127 non-proprietary compounds from several commercial sources. Presented also is the impact of this approach on false positive and false negative results. Copyright © 2012 John Wiley & Sons, Ltd.

  17. 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.

  18. [Cytotoxity of pomalidomide combined CAR-T cell for multiple myeloma cell RPMI8226 and U266].

    PubMed

    Wang, Lei; Zhang, Shuting; Ou, Jianfeng; Bai, Hai

    2015-06-01

    To observe the cytotoxity of CD138-CAR-T cells on human multiple myeloma cell RPMI8226 and U266 cells and explore the impact of pomalidomide on the cytotoxity of CD138-CAR-T on RPMI8226 and U266 cells. The cytotoxity of CD138-CAR-T and CD138-CAR-T combined pomalidomide on RPMI8226 and U266 was detected by CFSE/7AAD. The effctor cells were co-cultured with target cells at 5:1 for 18 h, and then the supernatant were collected and used for ELISA assays. After 18 h co-culture, the cytotoxity of CD138-CAR-T on RPMI8226 and U266 was significantiy higher than control (P<0.01). There was no significant change on the cytotoxity of pomalidoide combined with CD138-CAR-T on RPMI8226 and U266. The results showed that co-cultured system contribted to a markedly increased production of IFN-γ, after adding pomalidomide to the co-cultured system. It can significantly enhance the production of IFN-γ, compared with CD138-CAR-T alone. CD138-CAR-T had significantly cytotoxity on U266 and RPMI8226. Pomalidomide could promote CD138-CAR-T cells IFN-γ production.

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

    PubMed

    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; Williamson, Peter R

    2016-08-02

    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. Cryptococcosis is a neglected fungal meningitis that causes approximately half a million deaths annually. The most effective antifungal agent, amphotericin B, was developed in the 1950s, and no effective medicine has been developed for this disease since that time. A key aspect of amphotericin B's effectiveness is thought to be because of its ability to kill the fungus (fungicidal activity), rather than just stop or slow its growth. The present study utilized a recently identified fungicidal agent, bithionol, to identify potential fungicidal drug targets that can be used in developing modern fungicidal agents. A combined protein and genetic analysis approach was used to identify a class of enzymes, dehydrogenases, that the fungus uses to maintain homeostasis with regard to sugar nutrients. Similarities in the drug target site were found that resulted in simultaneous inhibition and killing of the fungus by bithionol. These studies thus

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

    PubMed

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

    2008-03-01

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

  1. 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

  2. High Structural Stress and Presence of Intraluminal Thrombus Predict Abdominal Aortic Aneurysm 18F-FDG Uptake: Insights From Biomechanics.

    PubMed

    Huang, Yuan; Teng, Zhongzhao; 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; Rudd, James H F

    2016-11-01

    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 ((18)F-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. Twenty-one patients (19 males) with AAAs below surgical threshold (AAA size was 4.10±0.54 cm) underwent (18)F-FDG positron emission tomography and contrast-enhanced computed tomography imaging. Structural stresses were calculated using finite element analysis. The relationship between maximum aneurysm (18)F-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 (18)F-FDG uptake (P<0.05). AAA structural stress correlated with (18)F-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 (18)F-FDG maximum standardized uptake value compared with regions with high thrombus burdens but low stress (median [interquartile range], 1.93 [1.60-2.14] versus 1.14 [0

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  4. Combined Treatment with the Mood Stabilizers Lithium and Valproate Produces Multiple Beneficial Effects in Transgenic Mouse Models of Huntington's Disease

    PubMed Central

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

    2011-01-01

    Emerging evidence suggests that the mood stabilizers lithium and valproate (VPA) have broad neuroprotective and neurotrophic properties, and that these occur via inhibition of glycogen synthase kinase 3 (GSK-3) and histone deacetylases (HDACs), respectively. Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by impaired movement, cognitive and psychiatric disturbances, and premature death. We treated N171-82Q and YAC128 mice, two mouse models of HD varying in genetic backgrounds and pathological progressions, with a diet containing therapeutic doses of lithium, VPA, or both. Untreated, these transgenic mice displayed a decrease in levels of GSK-3β serine 9 phosphorylation and histone H3 acetylation in the striatum and cerebral cortex around the onset of behavioral deficits, indicating a hyperactivity of GSK-3β and HDACs. Using multiple well-validated behavioral tests, we found that co-treatment with lithium and VPA more effectively alleviated spontaneous locomotor deficits and depressive-like behaviors in both models of HD mice. Furthermore, compared with monotherapy with either drug alone, co-treatment more successfully improved motor skill learning and coordination in N171-82Q mice, and suppressed anxiety-like behaviors in YAC128 mice. This combined treatment consistently inhibited GSK-3β and HDACs, and caused a sustained elevation in striatal as well as cortical brain-derived neurotrophic factor and heat shock protein 70. Importantly, co-treatment markedly prolonged median survival of N171-82Q mice from 31.6 to 41.6 weeks. Given that there is presently no proven treatment for HD, our results suggest that combined treatment with lithium and VPA, two mood stabilizers with a long history of safe use in humans, may have important therapeutic potential for HD patients. PMID:21796107

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

    PubMed

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs.

  6. Phevor Combines Multiple Biomedical Ontologies for Accurate Identification of Disease-Causing Alleles in Single Individuals and Small Nuclear Families

    PubMed Central

    Singleton, Marc V.; Guthery, Stephen L.; Voelkerding, Karl V.; Chen, Karin; Kennedy, Brett; Margraf, Rebecca L.; Durtschi, Jacob; Eilbeck, Karen; Reese, Martin G.; Jorde, Lynn B.; Huff, Chad D.; Yandell, Mark

    2014-01-01

    Phevor integrates phenotype, gene function, and disease information with personal genomic data for improved power to identify disease-causing alleles. Phevor works by combining knowledge resident in multiple biomedical ontologies with the outputs of variant-prioritization tools. It does so by using an algorithm that propagates information across and between ontologies. This process enables Phevor to accurately reprioritize potentially damaging alleles identified by variant-prioritization tools in light of gene function, disease, and phenotype knowledge. Phevor is especially useful for single-exome and family-trio-based diagnostic analyses, the most commonly occurring clinical scenarios and ones for which existing personal genome diagnostic tools are most inaccurate and underpowered. Here, we present a series of benchmark analyses illustrating Phevor’s performance characteristics. Also presented are three recent Utah Genome Project case studies in which Phevor was used to identify disease-causing alleles. Collectively, these results show that Phevor improves diagnostic accuracy not only for individuals presenting with established disease phenotypes but also for those with previously undescribed and atypical disease presentations. Importantly, Phevor is not limited to known diseases or known disease-causing alleles. As we demonstrate, Phevor can also use latent information in ontologies to discover genes and disease-causing alleles not previously associated with disease. PMID:24702956

  7. 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.

  8. Combining Machine Learning Systems and Multiple Docking Simulation Packages to Improve Docking Prediction Reliability for Network Pharmacology

    PubMed Central

    Hsin, Kun-Yi; Ghosh, Samik; Kitano, Hiroaki

    2013-01-01

    Increased availability of bioinformatics resources is creating opportunities for the application of network pharmacology to predict drug effects and toxicity resulting from multi-target interactions. Here we present a high-precision computational prediction approach that combines two elaborately built machine learning systems and multiple molecular docking tools to assess binding potentials of a test compound against proteins involved in a complex molecular network. One of the two machine learning systems is a re-scoring function to evaluate binding modes generated by docking tools. The second is a binding mode selection function to identify the most predictive binding mode. Results from a series of benchmark validations and a case study show that this approach surpasses the prediction reliability of other techniques and that it also identifies either primary or off-targets of kinase inhibitors. Integrating this approach with molecular network maps makes it possible to address drug safety issues by comprehensively investigating network-dependent effects of a drug or drug candidate. PMID:24391846

  9. 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.

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

    SciTech Connect

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

    2015-07-07

    Experimental studies (circular dichroism and ultra-violet (UV) absorption spectra) and large scale atomistic molecular dynamics simulations (accompanied by order parameter analyses) are combined to establish a number of remarkable (and unforeseen) structural transformations of protein myoglobin in aqueous ethanol mixture at various ethanol concentrations. The following results are particularly striking. (1) Two well-defined structural regimes, one at x{sub EtOH} ∼ 0.05 and the other at x{sub EtOH} ∼ 0.25, characterized by formation of distinct partially folded conformations and separated by a unique partially unfolded intermediate state at x{sub EtOH} ∼ 0.15, are identified. (2) Existence of non-monotonic composition dependence of (i) radius of gyration, (ii) long range contact order, (iii) residue specific solvent accessible surface area of tryptophan, and (iv) circular dichroism spectra and UV-absorption peaks are observed. Interestingly at x{sub EtOH} ∼ 0.15, time averaged value of the contact order parameter of the protein reaches a minimum, implying that this conformational state can be identified as a molten globule state. Multiple structural transformations well known in water-ethanol binary mixture appear to have considerably stronger effects on conformation and dynamics of the protein. We compare the present results with studies in water-dimethyl sulfoxide mixture where also distinct structural transformations are observed along with variation of co-solvent composition.

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

    PubMed Central

    Vanderveldt, Ariana; Green, Leonard; Myerson, Joel

    2014-01-01

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

  12. 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

  13. 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.

  14. Sutureless anastomosis of the small intestine and the colon in pigs using an absorbable intraluminal stent and fibrin glue.

    PubMed

    Detweiler, M B; Durastante, V; Verbo, A; Muttillo, I; Piantelli, M; Kobos, J W; Antinori, A; Granone, P; Magistrelli, P; Picciocchi, A

    1995-01-01

    A new sutureless anastomosis technique employing a sliding absorbable intraluminal nontoxic stent (SAINT) and fibrin glue with limited (minutes) stump margin pressure is described. Fifty-one (27 small intestine, 24 colon) SAINT anastomoses were performed in 31 Landrace pigs (25-35 kg). Controls consisted of 48 (26 small intestine, 22 colon) continuous single-layer submucosal anastomoses in 26 pigs. SAINTs, which dissolve in about 30-60 min, were formed from heated sucrose and water poured into handcrafted aluminum molds. Follow-up from 7 to 540 days showed no stenosis or anastomotic imperfections in the latter part of the experiment after the SAINT production and surgical techniques were improved. The SAINT group had fewer site adhesions, faster healing, less foreign body reaction, and fewer lymphocytes than the control group. Initial results indicate that the SAINT-fibrin glue procedure may be an effective sutureless anastomotic method from the duodenum to the sigmoid colon.

  15. Postprandial release of cholecystokinin after duodenum-preserving total pancreatectomy is independent of intraluminal pancreatic protease activity in dogs.

    PubMed

    Guicherit, O R; Gooszen, H G; Jansen, J B; van der Burg, M P; Lamers, C B

    1990-01-01

    The effect of meal stimulation, with and without the intraduodenal presence of pancreatic enzymes, on plasma cholecystokinin (CCK) release was studied in order to investigate the role of CCK in the putative feedback mechanism between intraduodenal pancreatic proteases and pancreatic enzyme secretion. Plasma CCK concentrations in response to a semiliquid meal, with and without the supplementation of exocrine pancreatic enzymes, were measured in 8 dogs after duodenum preserving pancreatectomy. With a well-balanced endocrine and exocrine substitution regimen all dogs were kept in good clinical condition, without steatorrhea or significant weight loss, and fasting plasma glucose levels within the normal range. Exocrine supplementation was stopped at least 3 days prior to tests. Basal plasma CCK levels after 3 days without exocrine supplementation (2.5 +/- 0.3 pM) did not significantly differ from the results with supplementation (3.0 +/- 0.5 pM) nor from the preoperative levels (2.3 +/- 0.3 pM). In addition, integrated plasma CCK responses to the meal without exocrine supplementation (330 +/- 37 pM.90 min) were not significantly different from the responses to the meal with exocrine supplementation (303 +/- 49 pM.90 min), or from the postprandial CCK response in the dogs with an intact pancreas preoperatively (390 +/- 100 pM.90 min). It is concluded that the release of CCK in dogs after total pancreatectomy is independent of intraluminal protease activity. It is therefore not likely that CCK mediates the putative feedback mechanism between intraluminal protease activity and pancreatic enzyme secretion in dogs.

  16. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  18. Mesenchymal stromal cells revert multiple myeloma cells to less differentiated phenotype by the combined activities of adhesive interactions and interleukin-6.

    PubMed

    Dezorella, Nili; Pevsner-Fischer, Meirav; Deutsch, Varda; Kay, Sigi; Baron, Shoshana; Stern, Ruth; Tavor, Sigal; Nagler, Arnon; Naparstek, Elizabeth; Zipori, Dov; Katz, Ben-Zion

    2009-07-01

    Multiple myeloma is characterized by the malignant growth of immunoglobulin producing plasma cells, predominantly in the bone marrow. The effects of primary human mesenchymal stromal cells on the differentiation phenotype of multiple myeloma cells were studied by co-culture experiments. The incubation of multiple myeloma cells with bone marrow-derived mesenchymal stromal cells resulted in significant reduction of the expression of the predominant plasma cell differentiation markers CD38 and CD138, and cell surface immunoglobulin light chain. While the down-regulation of CD138 by stromal cells was completely dependent on their adhesive interactions with the multiple myeloma cells, interleukin-6 induced specific down-regulation of CD38. Mesenchymal stromal cells or their conditioned media inhibited the growth of multiple myeloma cell line, thereby reducing the overall amounts of secreted light chains. Analysis of primary multiple myeloma bone marrow samples reveled that the expression of CD38 on multiple myeloma cells was not affected by adhesive interactions. The ex vivo propagation of primary multiple myeloma cells resulted in significant increase in their differentiation markers. Overall, the data indicate that the bone marrow-derived mesenchymal stromal cells revert multiple myeloma cells to less differentiated phenotype by the combined activities of adhesive interactions and interleukin-6.

  19. 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

  20. HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

    PubMed

    Rose, Rebecca; Lamers, Susanna L; Nolan, David J; Maidji, Ekaterina; Faria, N R; Pybus, Oliver G; Dollar, James J; Maruniak, Samuel A; McAvoy, Andrew C; Salemi, Marco; Stoddart, Cheryl A; Singer, Elyse J; McGrath, Michael S

    2016-10-15

    While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In

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

    PubMed

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

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

  2. 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

  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. Non-Contrast-Enhanced Silent Scan MR Angiography of Intracranial Anterior Circulation Aneurysms Treated with a Low-Profile Visualized Intraluminal Support Device.

    PubMed

    Takano, N; Suzuki, M; Irie, R; Yamamoto, M; Teranishi, K; Yatomi, K; Hamasaki, N; Kumamaru, K K; Hori, M; Oishi, H; Aoki, S

    2017-08-01

    The Low-Profile Visualized Intraluminal Support Device comprises a small-cell nitinol structure and a single-wire braided stent that provides greater metal coverage than previously reported intracranial stents, as well as assumed strong susceptibility artifacts. This study aimed to assess the benefits of non-contrast-enhanced MRA by using a Silent Scan (Silent MRA) for intracranial anterior circulation aneurysms treated with Low-Profile Visualized Intraluminal Support Device stents. Thirty-one aneurysms treated with Low-Profile Visualized Intraluminal Support Device stents were assessed by using Silent MRA, 3D TOF-MRA, and x-ray DSA. The quality of MRA visualization of the reconstructed artery was graded on a 4-point scale from 1 (not visible) to 4 (excellent). Aneurysm occlusion status was evaluated by using a 2-grade scale (total occlusion/remnant [neck or aneurysm]). Weighted κ statistics were used to evaluate interobserver and intermodality agreement. The mean scores ± SDs for Silent MRA and 3D TOF-MRA were 3.16 ± 0.79 and 1.48 ± 0.67 (P < .05), respectively, with substantial interobserver agreement (κ = 0.66). The aneurysm occlusion rates of the 2-grade scale (total occlusion/remnant [neck or aneurysm]) were 69%/31% for DSA, 65%/35% for Silent MRA, and 92%/8% for 3D TOF-MRA, respectively. The intermodality agreements were 0.88 and 0.30 for DSA/Silent MRA and DSA/3D TOF-MRA, respectively. Silent MRA seems to be useful for visualizing intracranial anterior circulation aneurysms treated with Low-Profile Visualized Intraluminal Support Device stents. © 2017 by American Journal of Neuroradiology.

  8. Combining multiple ECG features does not improve prediction of defibrillation outcome compared to single features in a large population of out-of-hospital cardiac arrests.

    PubMed

    He, Mi; Gong, Yushun; Li, Yongqin; Mauri, Tommaso; Fumagalli, Francesca; Bozzola, Marcella; Cesana, Giancarlo; Latini, Roberto; Pesenti, Antonio; Ristagno, Giuseppe

    2015-12-10

    Quantitative electrocardiographic (ECG) waveform analysis provides a noninvasive reflection of the metabolic milieu of the myocardium during resuscitation and is a potentially useful tool to optimize the defibrillation strategy. However, whether combining multiple ECG features can improve the capability of defibrillation outcome prediction in comparison to single feature analysis is still uncertain. A total of 3828 defibrillations from 1617 patients who experienced out-of-hospital cardiac arrest were analyzed. A 2.048-s ECG trace prior to each defibrillation without chest compressions was used for the analysis. Sixteen predictive features were optimized through the training dataset that included 2447 shocks from 1050 patients. Logistic regression, neural network and support vector machine were used to combine multiple features for the prediction of defibrillation outcome. Performance between single and combined predictive features were compared by area under receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and prediction accuracy (PA) on a validation dataset that consisted of 1381 shocks from 567 patients. Among the single features, mean slope (MS) outperformed other methods with an AUC of 0.876. Combination of complementary features using neural network resulted in the highest AUC of 0.874 among the multifeature-based methods. Compared to MS, no statistical difference was observed in AUC, sensitivity, specificity, PPV, NPV and PA when multiple features were considered. In this large dataset, the amplitude-related features achieved better defibrillation outcome prediction capability than other features. Combinations of multiple electrical features did not further improve prediction performance.

  9. 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

  10. Ambulatory 24-hour multichannel intraluminal impedance-pH monitoring and high resolution endoscopy distinguish patients with non-erosive reflux disease from those with functional heartburn.

    PubMed

    Chu, Chuanlian; Du, Quanlin; Li, Changqing; Zhang, Linlu; Zhou, Xiaoyan; Zuo, Fang; Zhang, Yanmin; Li, Fang; Xie, Guofeng; Li, Yanqing

    2017-01-01

    To assess the contribution of 24-h esophageal multichannel intraluminal impedance and pH (MII-pH) monitoring and high resolution endoscopy (HRE) with i-scan imaging in differentiating non erosive reflux disease (NERD) from functional heartburn (FH). This is a retrospective cohort study of patients with heartburn from the Endoscopy Unit. NERD patients and FH patients were defined by 24-h MII-pH monitoring and white light endoscopy. Minimal mucosal changes were assessed by HRE with i-scan imaging. Total of 156 consecutive patients with heartburn but without esophageal mucosal erosions were studied. Forty-eight of these subjects had NERD, with increased acid exposure time (AET) and positive SAP and/or SI. Eighteen had FH with normal AET and negative SAP and SI. When compared to FH patients and healthy controls, NERD patients had significantly increased number of total acid reflux episodes, as well as increased number of weakly acidic reflux episodes (p<0.01). The rate of proximal reflux episodes in NERD patients was higher than that of FH patients and healthy controls (p<0.01). Irregular or blurring of the Z-line (58.3%) and white mucosal turbidity (47.9%) were the most common endoscopic findings of minimal mucosal changes observed in this study. NERD patients had more prevalent minimal changes than FH patients and the controls (87.5%vs. 66.6%vs. 61.9%; p = 0.004) with sensitivity of 87.5%. Histopathological evaluation showed that NERD patients had significantly higher average scores of intercellular spaces dilation (2.82±0.9 vs. 1.2±0.6, p = 0.005) and papillae elongation (2.65±1.0 vs. 1.5±0.8, p = 0.014), but not for basal cell proliferation (1.6±1.3 vs. 1.0±0.9, p = 0.070). The histological scores of the NERD patients were 7.1±1.2, which were higher than those of FH patients (3.4±1.0, p = 0.004). Minimal mucosal changes could be useful markers to support clinical diagnosis of NERD. Combination of 24-h MII-pH monitoring and i-scan high resolution endoscopy

  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. Comparison of sutureless argon- and neodymium:YAG-welded ileo-ileal anastomosis using a biodegradable intraluminal stent

    NASA Astrophysics Data System (ADS)

    Costello, Anthony J.; Johnson, Douglas E.; Wishnow, Kenneth I.

    1990-06-01

    Sutureless end-to-end ileo-ileal intestinal anastomoses were successfully constructed with both the 1.06 jim neodymium:YAG and the 488/515-nm argon lasers. A 5-watt power setting was used with the neodymium:YAG, and various biologic solutions were added to the anastomotic seam during lasing. Power settings of 1.5, 3, 4, and 5 watts were used for argon lasing, with and without an exogenous chromophore. At the 4-watt argon setting, a continuous infusion of normal saline was dripped onto the anastomosis during lasing, replacing the chromophore. All bowel anastomoses were constructed with the aid of a biodegradable intraluminal stent that held the bowel ends in place during construction of the watertight ileal fusion and then completely degraded within 8 hours. We concluded that the neodymium:YAG seemed superior for tissue fusion using the techniques outlined, as it was associated with fewer anastomotic leaks. It appeared easier to determine the end-point of tissue fusion with the neodymium:YAG than the argon, because the tissue changes were more obvious during neodymium:YAG lasing. The deeper penetration into the bowel wall of neodymium:YAG laser energy may confer a welding advantage over the more shallow penetration of the argon wavelength.

  13. 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.

  14. 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.

  15. 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.

  16. "Rendezvous technique" for intraluminal vacuum therapy of anastomotic leakage of the jejunum.

    PubMed

    Krajinovic, K; Reimer, S; Kudlich, T; Germer, C T; Wiegering, A

    2016-12-01

    Anastomotic leakage (AL) is one of the most common and serious complications following visceral surgery. In recent years, endoluminal vacuum therapy has dramatically changed therapeutic options for AL, but its use has been limited to areas easily accessible by endoscope. We describe the first use of endoluminal vacuum therapy in the small intestine employing a combined surgical and endoscopic "rendezvous technique" in which the surgeon assists the endoscopic placement of an endoluminal vacuum therapy sponge in the jejunum by means of a pullback string. This technique led to a completely closed AL after 27 days and 7 changes of the endosponge. The combined surgical and endoscopic rendezvous technique can be useful in cases of otherwise difficult endosponge placement.

  17. [A case of postoperative recurrent breast cancer with multiple lung metastases that completely responded to combination therapy of docetaxel (TXT) and medroxyprogesterone acetate (MPA)].

    PubMed

    Mio, Hisaki

    2003-07-01

    A 54-year-old female had undergone surgery for breast cancer 5 years ago, after which she developed multiple lung metastases, in spite of treatment with various postoperative chemoendocrine therapies. The patient who had recurrent breast cancer with multiple lung metastases was treated with a combination of docetaxel (TXT) 80 mg/body three cycles, two courses of 40 mg/body four times and medroxyprogesterone acetate (MPA) 600 mg p.o. daily. Six months later, the lung metastases had completely disappeared on chest CT-scan. Complete remission has been maintained for one and half years. The use of combined chemoendocrine therapy with TXT and MPA is considered effective for recurrent breast cancer as second-line therapy.

  18. 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.

  19. Differential mobility spectrometry combined with multiple ion monitoring for bioanalysis of disulfide-bonded peptides with inefficient collision-induced dissociation fragmentation.

    PubMed

    Xia, Yuan-Qing; Ciccimaro, Eugene; Zheng, Naiyu; Zhu, Mingshe

    2017-01-01

    It is challenging to develop a multiple reaction monitoring (MRM) method for some disulfide-bonded peptides with inefficient collision-induced dissociation fragmentation. This study describes a new methodology using differential mobility spectrometry (DMS) combined with multiple ion monitoring (MIM) to enhance bioanalytical sensitivity for sunflower trypsin inhibitor. By combining DMS with MIM to monitor the intact precursor ion in Q1 and Q3 MS analyzers, a lower limit of quantitation at 0.125 ng/ml was achieved to quantify sunflower trypsin inhibitor in rat plasma, representing a 40-fold sensitivity improvement over MIM without DMS. DMS coupled with MIM method provides triple quadrupole MS users an effective means to overcome challenges in analyzing disulfide-bonded peptides or other analytes that do not have useful collision-induced dissociation fragment ions for MRM analysis.

  20. 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.

  1. 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…

  2. 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…

  3. 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

  4. Multiple immunoenzyme labeling using heat treatment combined with the polymer method: an analysis of the appropriate inactivation conditions of primary antibodies.

    PubMed

    Ikeda, Katsuhide; Suzuki, Takao; Tate, Genshu; Mitsuya, Toshiyuki

    2011-02-01

    Multiple immunoenzyme labeling is of considerable value to detect several antigens in the same specimen, although this technique is limited when the primary antibodies have been raised in the same animal species. Multiple immunoenzyme labeling using heat treatment is a simple, reliable and straightforward technique wherein the heat treatment prevents mixed labeling and cross-reaction. The present study determined the inactivation time for primary antibodies by heat treatment in order to apply this procedure to routine histopathological diagnosis and research, and found that the inactivation time differed among the primary antibodies. The secondary antibodies and the labeling enzyme were completely inactivated by heating for 10 min. Therefore, the inactivation of the primary antibodies is crucial to perform multiple immunoenzyme labeling using heat treatment. The sequential combination of the primary antibodies is also important; in the study presented here, an anti-thyroid transcription factor-1 (TTF-1) antibody should be used first and anti-cytokeratin AE1/AE3 antibody second, but not in the opposite sequence, to avoid a mixed-colour-labeling reaction. The present data provided the optimum combination of primary antibodies for multiple immunoenzyme labeling using heat treatment. Copyright © 2009 Elsevier GmbH. All rights reserved.

  5. Carfilzomib/pomalidomide single-agent or in combination with other agents for the management of relapsed/refractory multiple myeloma: a meta-analysis of 37 trials

    PubMed Central

    Zou, Yandun; Ma, Xiaoyan; Yu, Haiying; Hu, Chunling; Fan, Limei; Ran, Xuehong

    2017-01-01

    Purpose The use of carfilzomib/pomalidomide single-agent or in combination with other agents in patients with refractory/relapsed multiple myeloma (RRMM) was not clearly clarified in clinical practice. We sought to compile the available clinical reports to better understand the efficacy and safety of carfilzomib (CFZ) and pomalidomide (POM). Results Based on our research criteria, we identified 37 prospective studies that evaluated 1160 patients. Analysis of subgroup differences between carfilzomib single-agent and CFZ/DEX dual combination showed significantly(P < 0.001, I2 = 96.3%), suggesting the overall response rate (ORR) of 66% attained from CFZ/DEX dual combination seemed to be higher than that of 28% from carfilzomib single-agent. And, the same trend favoring CFZ/DEX dual combination was found in ≥VGPR and CBR analysis. The ORR of 31% attained from POM/DEX dual combination was superior to that of 19% from pomalidomide single-agent(P < 0.001, I2 = 94.4%). And, the same trend favoring POM/DEX dual combination was found in ≥VGPR and CBR analysis. However, the ORR of 83% attained from POM/BOR/DEX triplet combination was superior to that of 31% from POM/DEX dual combination(P < 0.001, I2 = 99.1%). And, the same trend favoring POM/BOR/DEX triplet combination was found in ≥VGPR analysis. Methods We searched published reports including carfilzomib and (or) pomalidomide therapy for RRMM who had received bortezomib and (or) lenalidomide. Conclusion Pomalidomide/Carfilzomib plus dexamethasone seemed to attain a superior response rate compared with pomalidomide/carfilzomib single-agent. Furthermore, the combination of pomalidomide, bortezomib and dexamethasone resulted in a much higher response rate compared with pomalidomide plus dexamethasone regimen. These results needed more validation in future trials. PMID:27458170

  6. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

    Neuroplasticity and neurorehabilitation have been extensively studied in animal models of stroke to guide clinical rehabilitation of stroke patients. Similar studies focused on traumatic brain injury (TBI) are lacking. The current study was designed to examine the effects of individual and combined rehabilitative approaches, previously shown to be beneficial following stroke, in an animal model of moderate/severe TBI, the controlled cortical impact (CCI). Rats received a unilateral CCI, followed by reach training, voluntary exercise, or unimpaired forelimb constraint, alone or in combination. Forelimb function was assessed at different time points post-CCI by tests of skilled reaching, motor coordination, and asymmetrical limb use. Following CCI, skilled reaching and motor coordination were significantly enhanced by combinations of rehabilitation strategies, not by individual approaches. The return of symmetrical limb use benefited from forelimb constraint alone. None of the rehabilitation strategies affected the size of injury, suggesting that enhanced behavioral function was not a result of neuroprotection. The current study has provided evidence that individual rehabilitation strategies shown to be beneficial in animal models of stroke are not similarly sufficient to enhance behavioral outcome in a model of TBI. Motor rehabilitation strategies for TBI patients may need to be more intense and varied. Future basic science studies exploring the underlying mechanisms of combined rehabilitation approaches in TBI as well as clinical studies comparing rehabilitation approaches for stroke versus TBI would prove fruitful. © The Author(s) 2015.

  10. 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.

  11. 64-element intraluminal ultrasound cylindrical phased array for transesophageal thermal ablation under fast MR temperature mapping: an ex vivo study.

    PubMed

    Melodelima, D; Salomir, R; Mougenot, C; Moonen, C; Cathignol, D

    2006-08-01

    This work was undertaken to investigate the feasibility of using a cylindrical phased array for transoesophaeal thermal ablation under magnetic resonance (MR) imaging guidance. Sixty-four transducers (0.45 mm wide by 15 mm tall), operating at 4.6 MHz, were spread around the periphery of a 10.6-mm-diam cylinder. The head of the applicator was covered with a 65-microm thick latex balloon attached using watertight seals. This envelope was inflated with degassed water to provide acoustic coupling between the transducer and the tissues. The underlying operating principle of this applicator is to rotate a plane ultrasound beam electronically. For this purpose, eight adjacent transducers were excited with appropriate delay times so as to generate a plane wave. The exposure direction was changed by exciting a different set of eight elements. Ex vivo experiments conducted on 47 samples of pig liver under MR temperature monitoring demonstrated the ability of this applicator to generate cylindrical or sector-based coagulation necroses at depths up to 19 mm with excellent angular precision by applying 20 W/cm2. MR thermometry was performed in "real-time" with segmented echo-planar imaging gradient echo sequences. The temporal resolution was approximately 3 s/ image. The average value for the temperature baseline in liver tissue close to the applicator was 0.3 degrees C (+/- 0.6 degrees C). The thermal dose delivered in tissues was computed on-line during temperature imaging. Excellent MR compatibility was demonstrated, all MR acquisitions were performed without susceptibility artifacts or radio-frequency interferences with the ultrasound device. Thermal lesions identified on post-treatment follow up showed good correlation with online MR thermometry data. The individual differences between measurements performed visually and using MRI thermal dose maps were about 11% of volume. This study demonstrated the feasibility of thermal ablation using a phased array intraluminal

  12. 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.

  13. Dual pH with Multichannel Intraluminal Impedance Testing in the Evaluation of Subjective Laryngopharyngeal Reflux Symptoms.

    PubMed

    Cumpston, Evan C; Blumin, Joel H; Bock, Jonathan M

    2016-12-01

    Minimal data exist to define the use of contemporary dual pH with multichannel intraluminal impedance (MII) probes integrating both pharyngeal acid and impedance sensors to evaluate laryngopharyngeal reflux (LPR) symptoms in a laryngology clinic population. This study was performed to review a series of patients tested with dual pH-MII for suspected LPR symptoms and to analyze pH-MII data findings for this patient cohort. Case series with planned data collection. Tertiary laryngology clinic. Patients with symptoms suggestive of possible LPR (dysphonia, chronic cough, globus sensation, subglottic stenosis,) were evaluated with a dual pH-MII system, as well as previously validated reflux finding score (RFS) and reflux symptom index (RSI) instruments. A total of 109 patients were evaluated with dual pH-MII studies between 2010 and 2015, with 51 (47%) studies interpreted as "positive" for evidence of significant LPR, 43 (39%) as "negative," and 15 (14%) as "equivocal." Dual pH-MII data analysis showed that positive studies had an average of 2.84 pharyngeal acid exposures below pH 4 (vs 0.28 for negative) and 46 episodes of proximal reflux exposure (either acid or nonacid) by impedance detection (vs 30.6 for negative). RSI scores were significantly different between positive and negative studies, while RFS scores were not. Dual pH-MII analysis is a useful supplementary tool to provide objective evidence of pharyngeal reflux exposure in patients with suspected LPR. RSI scores appear to correlate with objective evidence of acid exposure in the pharynx, while RFS scores do not. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  14. 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.

  15. 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

  16. Preparing for Multiple Births

    MedlinePlus

    ... Video Games, and the Internet Preparing for Multiple Births KidsHealth > For Parents > Preparing for Multiple Births Print ... a combination of both. The Risks of Multiple Births The most common risk involved with multiple births ...

  17. 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

  18. Combining Analyst and Waveform-Correlation-Based Arrival Time Measurements in the Bayesloc Multiple-Event Location Algorithm

    DTIC Science & Technology

    2011-09-01

    the i-th event. oi = the origin-time of the i-th event. Seismic signals originating from the events are recorded at multiple stations, and we denote...the likelihood of the differential arrival-time data where applicable. For example, when a Metrapolis random -walk sampler is used to propose a new lat...2004. Bondár, I., K.L. McLaughlin. A New Ground Truth Data Set For Seismic Studies, Seismological Research Letters Volume 80, Number 3, May/June

  19. High-intensity interval training combined with resistance training improves physiological capacities, strength and quality of life in multiple sclerosis patients: a pilot study.

    PubMed

    Zaenker, Pierre; Favret, Fabrice; Lonsdorfer, Evelyne; Muff, Guillaume; DE Seze, Jérôme; Isner-Horobeti, Marie-Eve

    2017-07-05

    Numerous studies have shown that mild-to-moderate intensity or resistance exercise training improves physical capacities such as, peak oxygen consumption, maximal tolerated power and strength in multiple sclerosis patients. However, few studies have evaluated the effects of high intensity interval training associated to with resistance training. Only few studies have analysed difference between men and women before and after combined training. Moreover, the evaluation of exercise between ambulatory multiple sclerosis patients without disability (EDSS 0- 3) and patients with disabilities (EDSS 3.5-5) was not largely published. The main objective of our study was to determine if high intensity interval training combined with resistance training improved aerobic and strength capacities as well as quality of life in multiple sclerosis patients and if gender and disabilities play a role in these changes. This study was an open-label uncontrolled study. The study was performed outside from conventional care facilities and including homebased training. 26 multiple sclerosis patients have completed the program (19 women/7men, Age 44.6+7.9years, Expanded Disability Status Score 2 (0-5)). We conducted a 12-week programme of high intensity interval training combined with resistance training at body weight. Peak oxygen consumption, maximal tolerated power, lactates, isokinetic strength of quadriceps and hamstrings (at 90°/sec, 180°/sec and 240°/sec) and quality of life were evaluated before and after the programme. Peak oxygen consumption and maximum tolerated power improved by 13.5% and 9.4%, respectively. Isokinetic muscle strength increased in both quadriceps and hamstrings at each speed, with a rebalancing of strength between the two legs in quadriceps. Quality of life was also enhanced in three domains. Women showed better improvements than men in VO2peak, maximal tolerated power, lactates at the end of test, and heart rate peak, strength in both quadriceps and

  20. 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

  1. 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.

  2. 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 marg